CN103083261A - Polysaccharide sulfate freeze-dried powder injection - Google Patents
Polysaccharide sulfate freeze-dried powder injection Download PDFInfo
- Publication number
- CN103083261A CN103083261A CN2013100525700A CN201310052570A CN103083261A CN 103083261 A CN103083261 A CN 103083261A CN 2013100525700 A CN2013100525700 A CN 2013100525700A CN 201310052570 A CN201310052570 A CN 201310052570A CN 103083261 A CN103083261 A CN 103083261A
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- China
- Prior art keywords
- freeze
- alginate
- propylene glycol
- sodium
- drying powder
- Prior art date
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- Granted
Links
- 239000000843 powder Substances 0.000 title claims abstract description 22
- -1 Polysaccharide sulfate Chemical class 0.000 title claims abstract description 7
- 238000002347 injection Methods 0.000 title abstract description 6
- 239000007924 injection Substances 0.000 title abstract description 6
- 229920001282 polysaccharide Polymers 0.000 title abstract description 6
- 239000005017 polysaccharide Substances 0.000 title abstract description 6
- HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical group OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 claims description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 21
- 239000000770 propane-1,2-diol alginate Substances 0.000 claims description 21
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 claims description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 21
- 235000011152 sodium sulphate Nutrition 0.000 claims description 21
- 235000010443 alginic acid Nutrition 0.000 claims description 17
- 229920000615 alginic acid Polymers 0.000 claims description 17
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 15
- 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 15
- 229940072056 alginate Drugs 0.000 claims description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
- 150000005690 diesters Chemical class 0.000 claims description 15
- 238000004108 freeze drying Methods 0.000 claims description 15
- 229910052708 sodium Inorganic materials 0.000 claims description 15
- 239000011734 sodium Substances 0.000 claims description 15
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims 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 claims description 11
- 229930195725 Mannitol Natural products 0.000 claims description 11
- 239000003963 antioxidant agent Substances 0.000 claims description 11
- 230000003078 antioxidant effect Effects 0.000 claims description 11
- 235000006708 antioxidants Nutrition 0.000 claims description 11
- 239000000594 mannitol Substances 0.000 claims description 11
- 235000010355 mannitol Nutrition 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 claims description 10
- 239000004475 Arginine Substances 0.000 claims description 10
- 229920002307 Dextran Polymers 0.000 claims description 10
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 10
- 229960001305 cysteine hydrochloride Drugs 0.000 claims description 10
- 230000001105 regulatory effect Effects 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 239000008215 water for injection Substances 0.000 claims description 10
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 9
- 239000008103 glucose Substances 0.000 claims description 9
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 229960003589 arginine hydrochloride Drugs 0.000 claims description 6
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 6
- 229960003121 arginine Drugs 0.000 claims description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 4
- 229960003180 glutathione Drugs 0.000 claims description 4
- 235000003969 glutathione Nutrition 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 239000003002 pH adjusting agent Substances 0.000 claims description 3
- 239000000600 sorbitol Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 description 12
- 239000002671 adjuvant Substances 0.000 description 4
- 239000013618 particulate matter Substances 0.000 description 4
- 239000013558 reference substance Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- AEMOLEFTQBMNLQ-BZINKQHNSA-N D-Guluronic Acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@@H](O)[C@H]1O AEMOLEFTQBMNLQ-BZINKQHNSA-N 0.000 description 2
- AEMOLEFTQBMNLQ-VANFPWTGSA-N D-mannopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-VANFPWTGSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 208000005793 Restless legs syndrome Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- AEMOLEFTQBMNLQ-UHFFFAOYSA-N beta-D-galactopyranuronic acid Natural products OC1OC(C(O)=O)C(O)C(O)C1O AEMOLEFTQBMNLQ-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000005261 decarburization Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000005374 membrane filtration Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 229910021653 sulphate ion Inorganic materials 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 206010018367 Glomerulonephritis chronic Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 229920001499 Heparinoid Polymers 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000199919 Phaeophyceae Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 239000002554 heparinoid Substances 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The application relates to a polysaccharide sulfate freeze-dried powder injection.
Description
Technical field
The application relates to a kind of alginate diester sodium freeze-drying powder.
Background technology
Propylene glycol alginate sodium sulfate (propyleneglycolalginatesodiumsulfate, PSS) be first ocean saccharide medicine of China of being developed by Chinese Marine University, be heparinoid drug, the clinical control that is mainly used in ischemic cardiac, cerebrovascular disease and hyperlipemia.PSS is mainly used in ischemic cerebrovascular such as cerebral thrombosis, cerebral embolism, transient ischemic attack and cardiovascular disease, as the control of the diseases such as hypertension, hyperlipoproteinemia, coronary heart diseases and angina pectoris existing more than 20 years of clinical application.PSS reaches 80% ~ 95% at the total effective rate aspect treatment cardio-cerebralvascular diseases clinical efficacy, and along with clinical application and research, find that also PSS also has good curative effect to the other disease, as cancer, diabetes, chronic glomerulonephritis, hepatitis, psoriasis, restless legs syndrome (restlesslegssyndrome, RLS) etc.
PSS is a kind of sulfated polysaccharides compounds, take Brown algae (as Thallus Laminariae (Thallus Eckloniae)) extract alginic acid as base stock, at first obtain oligomeric alginic acid through degraded, introduce propylene glycol ester group and sulfate group by the method for chemical modification again, with β-D-(1,4)-mannuronic acid (mannuronicacid, M) and α-L-(1,4)-guluronic acid (guluronicacid, G) be the polyanionic compound that basic sugar chain skeleton forms, have architectural feature and the physiological action of heparin sample.As a kind of polyose medicament, the relative molecular mass of PSS crude drug is generally 10000 ~ 20000, its dispersion of distribution＜1.80, and wherein the ratio of mannuronic acid and guluronic acid (M/G) is about 7:3.PSS is as the representative of marine polysaccharide class medicine, in anticoagulation, antithrombotic, blood fat reducing with improve the aspects such as microcirculation and have extremely important application.
Summary of the invention
The application's purpose is to provide a kind of novel alginate diester sodium freeze-drying powder, can overcome the defective of above-mentioned propylene glycol alginate sodium sulfate, improves the propylene glycol alginate sodium sulfate bioavailability, and is easy to use, absorbs soon, plays a role rapidly.
The present invention is by the screening to the propylene glycol alginate sodium sulfate injection prescription of freeze-drying powder, find to use specific excipient, and use simultaneously antioxidant and chelating agen, the polysaccharide sulphate for injection freeze-dried powder finished product that obtains stable high, impurity is few, and side effect is little, and safety is higher, have the advantages such as convenience stores and use, and production cost is low.
Alginate diester sodium freeze-drying powder of the present invention comprises the active constituents of medicine propylene glycol alginate sodium sulfate, excipient, antioxidant, chelating agen, pH adjusting agent.
Wherein said excipient is one or more of mannitol, sorbitol, dextran, glucose, lactose; Antioxidant is one or more of arginine, cysteine hydrochloride or glutathion; Chelating agen is disodiumedetate; The PH regulator is hydrochloric acid, citric acid, sodium hydroxide or sodium bicarbonate.
The applicant is surprised to find that, use the compositions of mannitol, glucose and dextran as excipient, and three's part by weight is 3: 5: 2; And antioxidant is selected the compositions of arginine and cysteine hydrochloride, and both part by weight is 2: 3; And use simultaneously the chelating agen disodiumedetate.The alginate diester sodium freeze-dried powder injection stability for preparing is high, and its related substances is low.
Technical solution of the present invention is (weight):
Propylene glycol alginate sodium sulfate 1-100 part
Excipient 1-500 part
Antioxidant 1-50 part
Chelating agen 1-50 part
PH adjusting agent is regulated pH to 5.5-6.5
Preparation method:
Take respectively propylene glycol alginate sodium sulfate, excipient, antioxidant and the chelating agen of recipe quantity, add in water for injection, fully be stirred to dissolve, add active carbon, absorption, decarburization is filtered.Regulate pH value to 5.5-6.5.After 0.22 μ m membrane filtration, fill is to cleaning in the cillin bottle of drying and sterilizing, and every fills 3mL, and half gland is opened freeze dryer, is cooled to-40 ℃, and lid is rolled in lyophilizing, checks packing.
Preferably, technical solution of the present invention is:
Propylene glycol alginate sodium sulfate 80g
The compositions of mannitol, glucose and dextran (three's part by weight is 3: 5: 2) 250g
The compositions of arginine and cysteine hydrochloride (both part by weight is 2: 3) 15g
Disodiumedetate 10g
Hydrochloric acid solution (0.1mol/l) is regulated pH to 6.5 in right amount
Water for injection adds to 1000ml
Embodiment 1:
Propylene glycol alginate sodium sulfate 80g
The compositions of mannitol, glucose and dextran (three's part by weight is 3: 5: 2) 250g
The compositions of arginine and cysteine hydrochloride (both part by weight is 2: 3) 15g
Disodiumedetate 10g
Hydrochloric acid solution (0.1mol/l) is regulated pH to 6.5 in right amount
Water for injection adds to 1000ml
Preparation method:
Take respectively propylene glycol alginate sodium sulfate, mannitol, glucose, dextran, arginine, cysteine hydrochloride and the disodiumedetate of recipe quantity, add in water for injection, fully be stirred to dissolve, add active carbon, absorption, decarburization is filtered.Hydrochloric acid solution is regulated pH value to 6.5.After 0.22 μ m membrane filtration, fill is to cleaning in the cillin bottle of drying and sterilizing, and every fills 3mL, and half gland is opened freeze dryer, is cooled to-40 ℃, and lid is rolled in lyophilizing, checks packing.
Embodiment 2
Propylene glycol alginate sodium sulfate 90g
The compositions of mannitol, glucose and dextran (three's part by weight is 3: 5: 2) 300g
The compositions of arginine and cysteine hydrochloride (both part by weight is 2: 3) 10g
Disodiumedetate 5g
Citric acid (0.1mol/l) is regulated pH to 5.5 in right amount
Water for injection adds to 1000ml
Preparation method is with embodiment 1
Embodiment 3
Propylene glycol alginate sodium sulfate 90g
Sorbitol 250g
Arginine 15g
Disodiumedetate 5g
Citric acid (0.1mol/l) is regulated pH to 6.0 in right amount
Water for injection adds to 1000ml
Preparation method is with embodiment 1
Embodiment 4
Propylene glycol alginate sodium sulfate 80g
Dextran 300g
Glutathion 15g
Disodiumedetate 12g
Sodium bicarbonate (0.1mol/l) is regulated pH to 6.5 in right amount
Water for injection adds to 1000ml
Preparation method is with embodiment 1
Embodiment 5
Propylene glycol alginate sodium sulfate 95g
Mannitol 270g
Cysteine hydrochloride 20g
Disodiumedetate 12g
Citric acid (0.1mol/l) is regulated pH to 5.5 in right amount
Water for injection adds to 1000ml
Preparation method is with embodiment 1
Embodiment 6
Propylene glycol alginate sodium sulfate 80g
Lactose 300g
Glutathion 15g
Disodiumedetate 10g
Sodium hydroxide (0.1mol/l) is regulated pH to 6.0 in right amount
Water for injection adds to 1000ml
Preparation method is with embodiment 1
The stability controlled trial
Embodiment 1-6 and reference substance (polysaccharide sulphate for injection freeze-dried powder, Qingdao ZhengDa HaiEr Pharmaceutical Co., Ltd), bottled, placed 6 months under (40 ± 2 ℃), relative humidity (75 ± 5) % condition, monitoring humidity, in 1,2,3,6 sampling at the end of month, propylene glycol alginate sodium sulfate in freeze-dried powder is carried out Detection of Stability, to investigate the preparation accelerated stability.Equally, sample bottle is loaded under (25 ± 2 ℃), relative humidity (60 ± 10) % condition and placed 24 months, and monitoring humidity is in 0,3,6,9,12,24 sampling at the end of month, propylene glycol alginate sodium sulfate in freeze-dried powder is carried out Detection of Stability, to investigate the preparation long-time stability.The results are shown in Table 1. and table 2.
The reference substance prescription:
Propylene glycol alginate sodium sulfate 50mg
Mannitol 180mg
Sodium bicarbonate is appropriate
Table 1 accelerated test result
Table 2 experiment steady in a long-term
Table 1 and table 2 result of the test show alginate diester sodium freeze-drying powder of the present invention with respect to prior art have advantages of aspect preparation stability outstanding; And selecting specific adjuvant is that the alginate diester sodium freeze-drying powder (embodiment 1,2) of excipient and antioxidant has unforeseeable stabilizing effect with respect to the alginate diester sodium freeze-drying powder (embodiment 3-6) of other adjuvants preparation.
Redissolve and test
Particulate matter assay method after redissolving: embodiment 1-6 and each 4 of reference substances are dissolved in 0.9% sodium chloride solution of 250ml, measure the particulate matter of solution after redissolving.The results are shown in Table 3.
Table 3
Table 3 data show that the embodiment of the present invention is obviously few with respect to the rear particulate matter of reference substance redissolution.Particularly having selected specific adjuvant is that particulate matter was still less after the alginate diester sodium freeze-drying powder (embodiment 1,2) of excipient and antioxidant redissolved with respect to the alginate diester sodium freeze-drying powder (embodiment 3-6) of other adjuvants preparation.
Claims (5)
1. alginate diester sodium freeze-drying powder, wherein active component is propylene glycol alginate sodium sulfate.
2. alginate diester sodium freeze-drying powder as claimed in claim 1 is comprising active constituents of medicine propylene glycol alginate sodium sulfate, excipient, antioxidant, chelating agen, pH adjusting agent.
3. alginate diester sodium freeze-drying powder as claimed in claim 2, wherein said excipient are one or more of mannitol, sorbitol, dextran, glucose, lactose; Antioxidant is one or more of arginine, cysteine hydrochloride or glutathion; Chelating agen is disodiumedetate; The PH regulator is hydrochloric acid, citric acid, sodium hydroxide or sodium bicarbonate.
4. alginate diester sodium freeze-drying powder as claimed in claim 2 or claim 3, wherein use the compositions of mannitol, glucose and dextran as excipient, and three's part by weight is 3: 5: 2; Antioxidant is selected the compositions of arginine and cysteine hydrochloride, and both part by weight is 2: 3; And use simultaneously the chelating agen disodiumedetate.
5. alginate diester sodium freeze-drying powder as claimed in claim 2 or claim 3, wherein
Propylene glycol alginate sodium sulfate 80g
The compositions of mannitol, glucose and dextran (three's part by weight is 3: 5: 2) 250g
The compositions of arginine and cysteine hydrochloride (both part by weight is 2: 3) 15g
Disodiumedetate 10g
Hydrochloric acid solution (0.1mol/l) is regulated pH to 6.5 in right amount
Water for injection adds to 1000ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310052570.0A CN103083261B (en) | 2013-02-18 | 2013-02-18 | Polysaccharide sulfate freeze-dried powder injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310052570.0A CN103083261B (en) | 2013-02-18 | 2013-02-18 | Polysaccharide sulfate freeze-dried powder injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103083261A true CN103083261A (en) | 2013-05-08 |
| CN103083261B CN103083261B (en) | 2014-03-19 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN201310052570.0A Active CN103083261B (en) | 2013-02-18 | 2013-02-18 | Polysaccharide sulfate freeze-dried powder injection |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688766A (en) * | 2015-03-31 | 2015-06-10 | 山东北大高科华泰制药有限公司 | Alginic sodium diester powder-injection pharmaceutical composition for injection and preparation method thereof |
| CN104922677A (en) * | 2015-05-27 | 2015-09-23 | 广州暨南生物医药研究开发基地有限公司 | Application of drug combination containing cepharanthine hydrochloride in preparing drug for treating leukopenia |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1481809A (en) * | 2003-07-29 | 2004-03-17 | 吉林市卓怡康纳制药有限公司 | Sodium bialginate for injection and its preparation method |
| CN101125126A (en) * | 2006-08-16 | 2008-02-20 | 丛繁滋 | Method for preparing medical freeze-dried powder (injection) preparation |
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2013
- 2013-02-18 CN CN201310052570.0A patent/CN103083261B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1481809A (en) * | 2003-07-29 | 2004-03-17 | 吉林市卓怡康纳制药有限公司 | Sodium bialginate for injection and its preparation method |
| CN101125126A (en) * | 2006-08-16 | 2008-02-20 | 丛繁滋 | Method for preparing medical freeze-dried powder (injection) preparation |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688766A (en) * | 2015-03-31 | 2015-06-10 | 山东北大高科华泰制药有限公司 | Alginic sodium diester powder-injection pharmaceutical composition for injection and preparation method thereof |
| CN104688766B (en) * | 2015-03-31 | 2018-06-01 | 山东北大高科华泰制药有限公司 | Polysaccharide sulphate for injection powder-injection pharmaceutical composition and preparation method |
| CN104922677A (en) * | 2015-05-27 | 2015-09-23 | 广州暨南生物医药研究开发基地有限公司 | Application of drug combination containing cepharanthine hydrochloride in preparing drug for treating leukopenia |
| CN104922677B (en) * | 2015-05-27 | 2018-06-12 | 广州康琪莱生物科技有限公司 | A kind of pharmaceutical composition of hydrochloric stephanine is preparing the application in treating leukopenic drug |
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| CN103083261B (en) | 2014-03-19 |
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