CN103083261B - Polysaccharide sulfate freeze-dried powder injection - Google Patents
Polysaccharide sulfate freeze-dried powder injection Download PDFInfo
- Publication number
- CN103083261B CN103083261B CN201310052570.0A CN201310052570A CN103083261B CN 103083261 B CN103083261 B CN 103083261B CN 201310052570 A CN201310052570 A CN 201310052570A CN 103083261 B CN103083261 B CN 103083261B
- Authority
- CN
- China
- Prior art keywords
- propylene glycol
- freeze
- sodium sulfate
- glycol alginate
- mannitol
- 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.)
- Active
Links
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) first ocean saccharide medicine of China that Shi You Chinese Marine University develops, for heparinoid drug, the clinical control that is mainly used in ischemic cardiac, cerebrovascular disease and hyperlipemia.PSS, existing more than 20 years of clinical application, is mainly used in ischemic cerebrovascular 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.PSS reaches 80% ~ 95% at the total effective rate aspect treatment cardio-cerebralvascular diseases clinical efficacy, and along with clinical application and research, also find that PSS also has good curative effect to other disease, as cancer, diabetes, chronic glomerulonephritis, hepatitis, psoriasis, restless legs syndrome (restlesslegssyndrome, RLS) etc.
PSS is a kind of sulfated polysaccharides compounds, Brown algae (as Thallus Laminariae (Thallus Eckloniae)) the extract alginic acid of take is base stock, first through degraded, obtain oligomeric alginic acid, by the method for chemical modification, introduce propylene glycol ester group and sulfate group 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, there is 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 object is to provide a kind of novel alginate diester sodium freeze-drying powder, can overcome the defect of above-mentioned propylene glycol alginate sodium sulfate, improves propylene glycol alginate sodium sulfate bioavailability, easy to use, absorbs soon, plays a role rapidly.
The present invention is by the screening to propylene glycol alginate sodium sulfate injection prescription of freeze-drying powder, find to use specific excipient, and use antioxidant and chelating agen simultaneously, the stability of the polysaccharide sulphate for injection freeze-dried powder finished product obtaining is high, impurity is few, and side effect is little, and safety is higher, there is the advantages such as convenience stores and uses, and production cost is low.
Alginate diester sodium freeze-drying powder of the present invention, comprises 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; PH regulator is hydrochloric acid, citric acid, sodium hydroxide or sodium bicarbonate.
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 the two part by weight is 2: 3; And use chelating agen disodiumedetate simultaneously.The alginate diester sodium freeze-dried powder injection stability 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 regulates pH to 5.5-6.5
Preparation method:
The propylene glycol alginate sodium sulfate, excipient, antioxidant and the chelating agen that take respectively recipe quantity, add in water for injection, is fully stirred to dissolve, and adds active carbon, absorption, and decarburization is filtered.Regulate pH value to 5.5-6.5.With 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 lyophilizing, rolls lid, 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 (the two part by weight is 2: 3) 15g
Disodiumedetate 10g
Hydrochloric acid solution (0.1mol/l) regulates 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 (the two part by weight is 2: 3) 15g
Disodiumedetate 10g
Hydrochloric acid solution (0.1mol/l) regulates pH to 6.5 in right amount
Water for injection adds to 1000ml
Preparation method:
The propylene glycol alginate sodium sulfate, mannitol, glucose, dextran, arginine, cysteine hydrochloride and the disodiumedetate that take respectively recipe quantity, add in water for injection, is fully stirred to dissolve, and adds active carbon, absorption, and decarburization is filtered.Hydrochloric acid solution regulates pH value to 6.5.With 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 lyophilizing, rolls lid, 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 (the two part by weight is 2: 3) 10g
Disodiumedetate 5g
Citric acid (0.1mol/l) regulates 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) regulates 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) regulates 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) regulates 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) regulates pH to 6.0 in right amount
Water for injection adds to 1000ml
Preparation method is with embodiment 1
Stability controlled trial
Embodiment 1-6 and reference substance (polysaccharide sulphate for injection freeze-dried powder, Qingdao ZhengDa HaiEr Pharmaceutical Co., Ltd), bottled, under (40 ± 2 ℃), relative humidity (75 ± 5) % condition, place 6 months, 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 to Detection of Stability, to investigate preparation accelerated stability.Equally, sample bottle is loaded under (25 ± 2 ℃), relative humidity (60 ± 10) % condition and places 24 months, and monitoring humidity, 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 to Detection of Stability, to investigate preparation long-time stability.The results are shown in Table 1. and table 2.
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 aspect preparation stability, have advantages of outstanding; And selecting specific adjuvant is that the alginate diester sodium freeze-drying powder (embodiment 3-6) that the alginate diester sodium freeze-drying powder (embodiment 1,2) of excipient and antioxidant is prepared with respect to other adjuvants has unforeseeable stabilizing effect.
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 after alginate diester sodium freeze-drying powder (embodiment 3-6) that the alginate diester sodium freeze-drying powder (embodiment 1,2) of excipient and antioxidant is prepared with respect to other adjuvants redissolves particulate matter is still less.
Claims (1)
1. an alginate diester sodium freeze-drying powder, wherein active component is propylene glycol alginate sodium sulfate,
Mannitol wherein, glucose and dextran three's part by weight is 3:5:2, the two part by weight of arginine and cysteine hydrochloride is 2:3, concentration of hydrochloric acid solution is 0.1mol/l, take respectively propylene glycol alginate sodium sulfate, mannitol, the compositions of glucose and dextran, the compositions of arginine and cysteine hydrochloride, disodiumedetate, add in water for injection, fully be stirred to dissolve, add active carbon, absorption, decarburization is filtered, regulate pH value to 6.5, with after 0.22 μ m membrane filtration, fill is to cleaning in the cillin bottle of drying and sterilizing, every dress 3mL, half gland, open freeze dryer, be cooled to-40 ℃, lyophilizing, roll lid, check, packing.
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 CN103083261A (en) | 2013-05-08 |
| CN103083261B true CN103083261B (en) | 2014-03-19 |
Family
ID=48196747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310052570.0A Active CN103083261B (en) | 2013-02-18 | 2013-02-18 | Polysaccharide sulfate freeze-dried powder injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103083261B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
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 |
-
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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103083261A (en) | 2013-05-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105983015B (en) | A pharmaceutical composition containing silibinin and VE | |
| CN105796492B (en) | Razaxaban nano suspension and preparation method thereof | |
| US11351184B2 (en) | Preparation of Pulsatilla saponin B4 for injection | |
| CN113425764B (en) | Application of herba cistanches Deserticolae total glycosides and echinacoside in preparing medicine for preventing and treating alcoholic liver injury and intestinal injury | |
| CN103083261B (en) | Polysaccharide sulfate freeze-dried powder injection | |
| de Almeida et al. | Exploring the potential of Dimorphandra gardneriana galactomannans as drug delivery systems | |
| CN104906121B (en) | Pharmaceutical composition containing tylonolide | |
| CN102379886A (en) | Scutellarin clinical preparation and preparation method thereof | |
| CN102525963A (en) | Netilmicin sulfate lyophiled powder injection and preparation method thereof | |
| CN103494776B (en) | Tamoxifen citrate freeze-dried powder injection | |
| CN100536868C (en) | Powder injection contg high content tanshin polyphenolic acid salts, and its preparation method | |
| CN102614493B (en) | Liquid pharmaceutical composition containing echinocandin antifungal agent caspofungin | |
| CN101585860A (en) | 4',5,6-trimethoxy scutellarin as well as preparation method and pharmaceutical composition thereof | |
| CN103083268B (en) | Polysaccharide sulfate dispersible tablet | |
| WO2016169489A1 (en) | Application of forsythin, forsythin derivative, composition of forsythin and forsythin lignans in preparing medicine or health care product for preventing or/and treating liver injury | |
| CN101376022B (en) | Medicament composition containing defibrase modified by PEG | |
| CN103169682B (en) | Polysaccharide sulfate tablet and preparation method of polysaccharide sulfate tablet | |
| CN104688766B (en) | Polysaccharide sulphate for injection powder-injection pharmaceutical composition and preparation method | |
| CN103083248B (en) | Polysaccharide sulfate dry suspension | |
| CN103211772B (en) | Etoposide lyophilized powder for injection | |
| CN104095841B (en) | Neogambogic acid application in treatment or the prevention Fibrotic medicine of internal organs | |
| CN115040505B (en) | Glabridin compound and preparation method and application thereof | |
| CN103127027B (en) | Polysaccharide sulphate dropping pill | |
| CN107857786B (en) | naringenin-7-O-glucoside-6' -succinate and application thereof in preparation of antibacterial or osteoporosis treatment medicines | |
| CN104922081B (en) | A kind of Cepharantin hydrochloride freeze-dried powder, preparation method and applications |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP02 | Change in the address of a patent holder |
Address after: 266103 Qingdao economic and Technological Development Zone, unity Road, No. 3601, Shandong Patentee after: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. Address before: 266103 Haier Road, Shandong, Qingdao, No. 1 Patentee before: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 266103 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Patentee after: Zhengda Pharmaceutical (Qingdao) Co., Ltd. Address before: 266103 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Patentee before: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. |