CN102670529A - Levo-pantoprazole sodium freeze-dried powder composition for injection and preparation method thereof - Google Patents
Levo-pantoprazole sodium freeze-dried powder composition for injection and preparation method thereof Download PDFInfo
- Publication number
- CN102670529A CN102670529A CN2012101714550A CN201210171455A CN102670529A CN 102670529 A CN102670529 A CN 102670529A CN 2012101714550 A CN2012101714550 A CN 2012101714550A CN 201210171455 A CN201210171455 A CN 201210171455A CN 102670529 A CN102670529 A CN 102670529A
- Authority
- CN
- China
- Prior art keywords
- injection
- pantoprazole sodium
- levo
- preparation
- dried powder
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 25
- 238000002347 injection Methods 0.000 title claims abstract description 18
- 239000007924 injection Substances 0.000 title claims abstract description 18
- 239000000843 powder Substances 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 13
- 229960004048 pantoprazole sodium Drugs 0.000 title abstract 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
- 238000001914 filtration Methods 0.000 claims abstract description 12
- 239000004475 Arginine Substances 0.000 claims abstract description 11
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 238000001035 drying Methods 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 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 claims abstract description 6
- 229930195725 Mannitol Natural products 0.000 claims abstract description 6
- 238000004108 freeze drying Methods 0.000 claims abstract description 6
- 235000010355 mannitol Nutrition 0.000 claims abstract description 6
- 239000000594 mannitol Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims abstract description 6
- 239000008215 water for injection Substances 0.000 claims abstract description 6
- YNWDKZIIWCEDEE-SNYZSRNZSA-N sodium;5-(difluoromethoxy)-2-[(s)-(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-ide Chemical compound [Na+].COC1=CC=NC(C[S@](=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC YNWDKZIIWCEDEE-SNYZSRNZSA-N 0.000 claims description 19
- 238000010792 warming Methods 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000012982 microporous membrane Substances 0.000 claims description 5
- 238000000859 sublimation Methods 0.000 claims description 5
- 230000008022 sublimation Effects 0.000 claims description 5
- 230000001186 cumulative effect Effects 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 238000007599 discharging Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000001816 cooling Methods 0.000 abstract 2
- 238000010438 heat treatment Methods 0.000 abstract 2
- 239000004615 ingredient Substances 0.000 abstract 1
- 239000002075 main ingredient Substances 0.000 abstract 1
- 239000012528 membrane Substances 0.000 abstract 1
- 238000001471 micro-filtration Methods 0.000 abstract 1
- 238000004806 packaging method and process Methods 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 208000025865 Ulcer Diseases 0.000 description 21
- 231100000397 ulcer Toxicity 0.000 description 21
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 9
- 210000004877 mucosa Anatomy 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 210000004211 gastric acid Anatomy 0.000 description 6
- 208000007107 Stomach Ulcer Diseases 0.000 description 5
- 201000005917 gastric ulcer Diseases 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
- 210000002784 stomach Anatomy 0.000 description 5
- IQPSEEYGBUAQFF-SANMLTNESA-N 6-(difluoromethoxy)-2-[(s)-(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(C[S@](=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-SANMLTNESA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000590002 Helicobacter pylori Species 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 230000027119 gastric acid secretion Effects 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 229940037467 helicobacter pylori Drugs 0.000 description 3
- 206010010075 Coma hepatic Diseases 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000003628 erosive effect Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 201000001059 hepatic coma Diseases 0.000 description 2
- 208000007386 hepatic encephalopathy Diseases 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 230000008263 repair mechanism Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229940057216 branchamin Drugs 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 231100000749 chronicity Toxicity 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 238000013021 overheating Methods 0.000 description 1
- 210000001711 oxyntic cell Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000029547 smooth muscle hypertrophy Effects 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- -1 stress Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Classifications
-
- 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
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a levo-pantoprazole sodium freeze-dried powder composition for injection and a preparation method of the composition, and relates to the field of medicines. The major ingredients of the composition are levo-pantoprazole sodium and arginine, and the specific steps for preparing the freeze-dried powder composition are as follows: adding 0.1-99.9% by weight of levo-pantoprazole sodium, 99.9-0.1% by weight of arginine and mannitol 5-10 times of the main ingredients into water for injection; stirring and dissolving, then, adding a NaOH solution; regulating the pH value to 11.0; adding active carbon in 0.1% of the total volume and stirring for 30 minutes; filtering and removing the active carbon, and then filtering the liquid medicine through 0.45 mum and 0.22 mum microfiltration membranes; packaging and feeding into a freeze dryer; cooling to the temperature below 40 DEG C, keeping the temperature for 2 hours, then, slowly heating to -5 to 0 DEG C for lyophilization, and then heating to 35 DEG C; keeping the temperature for 3 hours; and discharging from the package after cooling and drying so as to obtain the levo-pantoprazole sodium freeze-dried powder composition for injection. The levo-pantoprazole sodium freeze-dried powder composition for injection and the preparation method of the composition have the following advantages: liquid can be conveniently processed, and the aseptic operation process is simplified; the stability of the preparation is improved; the product can be dried without being thermally treated; and the rehydration capability (dissolubility) of the preparation is improved.
Description
Technical field:
The present invention relates to field of medicaments, relate in particular to a kind of injection L-pantoprazole sodium freeze dry composition and method of making the same.
Background technology:
Gastric ulcer is one of commonly encountered diseases in the population of China, frequently-occurring disease.Its take place mainly with the damage factor of gastroduodenal mucosa and mucosa self-defense reparation factor between loss of equilibrium relevant.Helicobacter pylori (H. pylori) infection, NSAID (NSAID is like aspirin), gastric acid secretion be the commonly encountered diseases that causes ulcer unusually because of.Typical ulcer pain has the characteristics of chronicity, periodicity and rhythmicity.
In the gastral cavity, gastric acid and pepsin are digestion materials important in the gastric juice.Gastric acid is the highly acid material, has stronger aggressivity; Pepsin has the effect of aminosal; Can destroy the protein on the coat of the stomach, yet, in the presence of these factors of erosion; Gastrointestinal tract still can be resisted and keep the integrity of mucosa and the function of self, and it mainly is also to have series of defence and repair mechanism because of stomach, duodenum mucosa.We are referred to as damage mechanism with gastric acid and pepsic harmful aggressivity, and defence and the repair mechanism that gastrointestinal tract self has is referred to as protection mechanism.Think that at present the protection mechanism of normal person's gastroduodenal mucosa is enough to resist gastric acid and pepsic erosion.But, when some factor has damaged that certain link in the protection mechanism just possibly take place that gastric acid and protease corrode self mucosa and the formation that causes ulcer.When excessive gastric acid secretion also possibly cause ulcer to take place considerably beyond the defence of mucosa and repair.In recent years research shows, helicobacter pylori and NSAID be the infringement gastrointestinal protection mechanism most commonly encountered diseases that causes the ulcer morbidity because of, gastric acid plays a crucial role in ulcer.In addition, medicine, stress, hormone also can cause the generation of ulcer, and various psychological factors and bad dietetic life custom can be brought out the appearance of ulcer.
Summary of the invention:
The object of the present invention is to provide a kind of injection L-pantoprazole sodium freeze dry composition and method of making the same, said composition has synergism in vivo, can treat gastric ulcer clinically, the repairing ulcer wound, and the treatment digestive tract ulcer, curative effect is rapid.
Concrete technical scheme of the present invention is:
A kind of injection L-pantoprazole sodium freeze dry compositions is characterized in that the principal agent of said composition is: mass percent, 0.1%～99.9% L-pantoprazole sodium and 99.9%～0.1% arginine.
More than one principal agents of stating compositions prepare the method for injection freeze-dried powder, it is characterized in that, the concrete operations step is:
(1) be that the mannitol of 5～10 times of 0.1%～99.9% L-pantoprazole sodium, 99.9%～0.1% arginine and principal agents is added in the water for injection with mass percent;
(2) add NaOH solution after the stirring and dissolving and regulate pH value 11.0;
(3) active carbon that adds cumulative volume 0.1% stirred 30 minutes;
(4) filtering active carbon, medicinal liquid are again through 0.45 μ m and 0.22 μ m filtering with microporous membrane;
(5) canned, send in the freezer dryer;
(6) be cooled to-40 ℃, be incubated after 2 hours, slowly be warming up to-5 ℃～0 ℃ sublimation drying, be warming up to 35 ℃ again after, be incubated 3 hours;
(7) lyophilization finishes, and outlet promptly gets injection L-pantoprazole sodium freeze dry compositions.
L-pantoprazole sodium acts on the key enzyme H+-K+ATP enzyme in the whole last step of parietal cell gastric acid secretion, makes its irreversible inactivation, presses down the stronger and persistent of acid effect.L-pantoprazole sodium promotes that rapid speed, the healing rate of ulcer healing are higher; Be applicable to the treatment when various intractable ulcers or NSAID ulcer patient can not stop using NSAID; Also can be used for Helicobacter pylori eradication for treatment with antibiotic synergism, be the first-selected medication of gastric ulcer therefore.
Arginine (Arg) is a Branchamin, participates in ornithine cycle, under extractum hepatis propylhomoserin enzyme activity, promotes ammonia to be converted into nontoxic carbamide by discharging in the urine, to reduce blood ammonia.Being mainly used in blood ammonia increases the hepatic coma and all kinds of hepatic coma that cause and avoids the patient with sodium glutamate.New pharmacological research is found: Arg is the physiological prerequisite of nitric oxide (NO), after NO synzyme (NOS) effect, generates NO.NO has multiple physiological activity in vivo: vasodilator, antiplatelet aggregation, antithrombotic formation and resisting vascular smooth muscle hypertrophy etc.Thereby, ectogenic Arg is provided as the substrate that synthesizes NO, and through the Arg-NO path, promoting that NO concentration increases in the body, Arg can play the restorative effect of ulcer wound of quickening in clinical.
Single L-pantoprazole preparation of sodium can only play the effect of treatment, can only lean on the human body self reparation.Single arginine but can not play the purpose of treatment.So gastric ulcer has not only been treated in both combinations, can also accomplish the repairing ulcer area, thereby improve therapeutic effect.
The present invention has following advantage with freeze-dry process production injection L-pantoprazole sodium freeze dry compositions: 1) liquid is easy to process, has simplified the sterile procedures process; 2) improved stability of formulation; 3) need not just can remove the moisture in the product through Overheating Treatment; 4) strengthened rehydration (dissolving) property of preparation.
The specific embodiment:
For technological means, creation characteristic that the present invention is realized, reach purpose and effect and be easy to understand and understand, below in conjunction with specific embodiment, further set forth the present invention.
The preparation of embodiment one, injection L-pantoprazole composition of sodium freeze-dried powder is in 1000
1. write out a prescription
2. preparation technology
With recipe quantity L-pantoprazole sodium, arginine and mannitol be added in the water for injection, add NaOH solution after the stirring and dissolving and regulate pH value 11.0, add 0.1% active carbon and stirred the filtering active carbon 30 minutes; Medicinal liquid is again through 0.45 μ m and 0.22 μ m filtering with microporous membrane, and is canned, sends in the freezer dryer, is cooled to-40 ℃; Be incubated after 2 hours, slowly be warming up to-5 ℃～0 ℃ sublimation drying, be warming up to 35 ℃ again after; Be incubated 3 hours, lyophilization finishes, outlet.
The preparation of embodiment two, injection L-pantoprazole composition of sodium freeze-dried powder is in 1000
1. write out a prescription
2. preparation technology
With recipe quantity L-pantoprazole sodium, arginine and mannitol be added in the water for injection, add NaOH solution after the stirring and dissolving and regulate pH value 11.0, add 0.1% active carbon and stirred the filtering active carbon 30 minutes; Medicinal liquid is again through 0.45 μ m and 0.22 μ m filtering with microporous membrane, and is canned, sends in the freezer dryer, is cooled to-40 ℃; Be incubated after 2 hours, slowly be warming up to-5 ℃～0 ℃ sublimation drying, be warming up to 35 ℃ again after; Be incubated 3 hours, lyophilization finishes, outlet.
The preparation of embodiment three, injection L-pantoprazole composition of sodium freeze-dried powder is in 1000
1. write out a prescription
2. preparation technology
With recipe quantity L-pantoprazole sodium, arginine and mannitol be added in the water for injection, add NaOH solution after the stirring and dissolving and regulate pH value 11.0, add 0.1% active carbon and stirred the filtering active carbon 30 minutes; Medicinal liquid is again through 0.45 μ m and 0.22 μ m filtering with microporous membrane, and is canned, sends in the freezer dryer, is cooled to-40 ℃; Be incubated after 2 hours, slowly be warming up to-5 ℃～0 ℃ sublimation drying, be warming up to 35 ℃ again after; Be incubated 3 hours, lyophilization finishes, outlet.
Experimental data
50 of SD rat.Fasting 24h before the test.Under etherization open the abdominal cavity, the glass tubing of internal diameter 5mm, long 30mm vertically is positioned on the body of stomach serosal surface, in tube chamber, add glacial acetic acid 0. 2ml, dip in out glacial acetic acid with cotton swab behind the 1.5min, the suture operation otch.The postoperative normal diet was divided into 5 groups with animal in second day: matched group 1 (distilled water), matched group 2 (injection L-pantoprazole sodium), treatment group 1 (embodiment one), treatment group 2 (embodiment two), treatment group 3 (embodiment three) at random; Successive administration 15d.Dissect and take out stomach, and use formaldehyde fixed, cut stomach open along greater gastric curvature, open and flat on glass plate, measure ulcer footpath d1, d2 anyhow.Calculate ulcer area S (mm2) as UI with formula S=π * (d1/2) * (d2/2), and calculate ulcer healing rate and ulcer inhibition rate.The result sees the following form
Show that through experimental data embodiment one, two, three all has the good curing effect to ulcer, the cure rate of treatment group 1,2,3 has excellent curative with L-pantoprazole sodium (matched group 2) height to gastric ulcer than single, and can the repairing ulcer area.
More than show and described ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; The present invention is not restricted to the described embodiments; That describes in the foregoing description and the description just explains principle of the present invention; Under the prerequisite that does not break away from spirit and scope of the invention, the present invention also has various changes and modifications, and these variations and improvement all fall in the scope of the invention that requires protection.The present invention requires protection domain to be defined by appending claims and equivalent thereof.
Claims (2)
1. an injection L-pantoprazole sodium freeze dry compositions is characterized in that the principal agent of said composition is: mass percent, 0.1%～99.9% L-pantoprazole sodium and 99.9%～0.1% arginine.
2. the principal agent with the said compositions of claim 1 prepares the method for injection freeze-dried powder, it is characterized in that the concrete operations step is:
(1) be that the mannitol of 5～10 times of 0.1%～99.9% L-pantoprazole sodium, 99.9%～0.1% arginine and principal agents is added in the water for injection with mass percent;
(2) add NaOH solution after the stirring and dissolving and regulate pH value 11.0;
(3) active carbon that adds cumulative volume 0.1% stirred 30 minutes;
(4) filtering active carbon, medicinal liquid are again through 0.45 μ m and 0.22 μ m filtering with microporous membrane;
(5) canned, send in the freezer dryer;
(6) be cooled to-40 ℃, be incubated after 2 hours, slowly be warming up to-5 ℃～0 ℃ sublimation drying, be warming up to 35 ℃ again after, be incubated 3 hours;
(7) lyophilization finishes, and outlet promptly gets injection L-pantoprazole sodium freeze dry compositions.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101714550A CN102670529A (en) | 2012-05-29 | 2012-05-29 | Levo-pantoprazole sodium freeze-dried powder composition for injection and preparation method thereof |
| PCT/CN2012/084939 WO2013177907A1 (en) | 2012-05-29 | 2012-11-21 | Injection-use levorotatory-pantoprazole sodium lyophilized powder composition and preparation method therefor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101714550A CN102670529A (en) | 2012-05-29 | 2012-05-29 | Levo-pantoprazole sodium freeze-dried powder composition for injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102670529A true CN102670529A (en) | 2012-09-19 |
Family
ID=46803527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101714550A Pending CN102670529A (en) | 2012-05-29 | 2012-05-29 | Levo-pantoprazole sodium freeze-dried powder composition for injection and preparation method thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN102670529A (en) |
| WO (1) | WO2013177907A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013177907A1 (en) * | 2012-05-29 | 2013-12-05 | 海南卫康制药(潜山)有限公司 | Injection-use levorotatory-pantoprazole sodium lyophilized powder composition and preparation method therefor |
| CN115444826A (en) * | 2022-10-14 | 2022-12-09 | 海南锦瑞制药有限公司 | Preparation method of pantoprazole sodium for injection |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1813729A (en) * | 2005-02-02 | 2006-08-09 | 兰贝克赛实验室有限公司 | Injectable formulations of benzimidazole compounds |
| CN1853628A (en) * | 2005-04-29 | 2006-11-01 | 一洋药品株式会社 | Preparing method for injection containing benzimidazole derivative |
| CN101229138A (en) * | 2008-01-18 | 2008-07-30 | 山东罗欣药业股份有限公司 | Pantoprazole sodium freeze-dried powder injection and preparing method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670529A (en) * | 2012-05-29 | 2012-09-19 | 海南卫康制药(潜山)有限公司 | Levo-pantoprazole sodium freeze-dried powder composition for injection and preparation method thereof |
-
2012
- 2012-05-29 CN CN2012101714550A patent/CN102670529A/en active Pending
- 2012-11-21 WO PCT/CN2012/084939 patent/WO2013177907A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1813729A (en) * | 2005-02-02 | 2006-08-09 | 兰贝克赛实验室有限公司 | Injectable formulations of benzimidazole compounds |
| CN1853628A (en) * | 2005-04-29 | 2006-11-01 | 一洋药品株式会社 | Preparing method for injection containing benzimidazole derivative |
| CN101229138A (en) * | 2008-01-18 | 2008-07-30 | 山东罗欣药业股份有限公司 | Pantoprazole sodium freeze-dried powder injection and preparing method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 乐桥良等: "一氧化氮在潘托拉唑对大鼠胃黏膜损伤保护中的作用", 《第四军医大学学报》 * |
| 乐桥良等: "潘托拉唑对胃黏膜损伤保护作用及其机制", 《世界华人消化杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013177907A1 (en) * | 2012-05-29 | 2013-12-05 | 海南卫康制药(潜山)有限公司 | Injection-use levorotatory-pantoprazole sodium lyophilized powder composition and preparation method therefor |
| CN115444826A (en) * | 2022-10-14 | 2022-12-09 | 海南锦瑞制药有限公司 | Preparation method of pantoprazole sodium for injection |
| CN115444826B (en) * | 2022-10-14 | 2023-07-21 | 海南锦瑞制药有限公司 | Preparation method of pantoprazole sodium for injection |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013177907A1 (en) | 2013-12-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102657650A (en) | Esomeprazole sodium lyophilized powder composition for injection and preparation method thereof | |
| CN104288504B (en) | A kind of Chinese medicine ointment formulation for treating burn, scald and preparation method thereof | |
| CN102058593A (en) | Combination medicament of ilaprazole sodium and preparation process thereof | |
| ES2340603T3 (en) | BACTERIAL CULTURE WITH SUPPRESSING EFFECT OF THE DEVELOPMENT OF DERMATITIS AND ACCELERATOR OF WOUND AND PRODUCT CICATRIZATION USING IT. | |
| CN109758580A (en) | Treatment preparation and its application of injury to alimentary tract mucous membrane surface are sprayed to suitable for gastroscope | |
| CN109939183A (en) | A kind of oral skin-generating oil and its preparation method and application for treating oral cavity burn and scald | |
| CN101632754B (en) | Chinese medicinal composition for treating pharyngitis and preparation method thereof | |
| CN102670528A (en) | Pantoprazole sodium lyophilized powder composition for injection and preparation method thereof | |
| CN102670529A (en) | Levo-pantoprazole sodium freeze-dried powder composition for injection and preparation method thereof | |
| CN104628657A (en) | Class of compounds for treating ischemic brain damage and purpose thereof | |
| CN101744815A (en) | Composite medicament of omeprazole sodium | |
| CN104906132B (en) | A kind of plaster for preventing and treating lamb stomatitis | |
| KR101976560B1 (en) | Method for producing dry extracts | |
| CN112891437A (en) | Traditional Chinese medicine composition for treating gastric ulcer and preparation method thereof | |
| CN112773833A (en) | Traditional Chinese medicine prescription for treating recurrent aphthae and preparation method thereof | |
| CN103301126B (en) | Pantoprazole sodium composition for injection | |
| CN104146558A (en) | Medical pillow capable of treating rhinitis | |
| JPS6036413A (en) | Agent for promoting recovery from inflammation | |
| CN112755058B (en) | Application of devilpepper ethanol extract in preparation of medicine for relaxing and pre-contracting tracheal smooth muscle | |
| CN106729672A (en) | A kind of composition for treating upper respiratory tract mucositis and its application | |
| CN102091070A (en) | Rabeprazole sodium combined medicament and preparation process thereof | |
| CN103719616A (en) | Feed for treating bloody flux of pigs and preparation method of feed | |
| CN101766615B (en) | Pantoprazole sodium combined drug | |
| CN101708284B (en) | Medicament for treating hemorrhoids | |
| CN110876740B (en) | Use of volvalerenal K for repairing skin lesions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120919 |