CN104606130B - A kind of Tropisetron HCl parenteral solution and preparation method thereof - Google Patents
A kind of Tropisetron HCl parenteral solution and preparation method thereof Download PDFInfo
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- CN104606130B CN104606130B CN201410852680.XA CN201410852680A CN104606130B CN 104606130 B CN104606130 B CN 104606130B CN 201410852680 A CN201410852680 A CN 201410852680A CN 104606130 B CN104606130 B CN 104606130B
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- 229960003688 tropisetron Drugs 0.000 title claims abstract description 79
- 239000003182 parenteral nutrition solution Substances 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- UIVFDCIXTSJXBB-ITGUQSILSA-N tropisetron Chemical compound C1=CC=C[C]2C(C(=O)O[C@H]3C[C@H]4CC[C@@H](C3)N4C)=CN=C21 UIVFDCIXTSJXBB-ITGUQSILSA-N 0.000 title claims abstract 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229960000583 acetic acid Drugs 0.000 claims abstract description 20
- 239000011780 sodium chloride Substances 0.000 claims abstract description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 17
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical class [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims abstract description 16
- 238000001914 filtration Methods 0.000 claims abstract description 14
- 239000008215 water for injection Substances 0.000 claims abstract description 14
- 239000001632 sodium acetate Substances 0.000 claims abstract description 9
- 235000017281 sodium acetate Nutrition 0.000 claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 230000001954 sterilising effect Effects 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 13
- 238000007689 inspection Methods 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 238000013329 compounding Methods 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 5
- 238000004806 packaging method and process Methods 0.000 claims description 5
- 239000003708 ampul Substances 0.000 claims description 4
- 238000005374 membrane filtration Methods 0.000 claims description 4
- BDKZHNJTLHOSDW-UHFFFAOYSA-N [Na].CC(O)=O Chemical compound [Na].CC(O)=O BDKZHNJTLHOSDW-UHFFFAOYSA-N 0.000 claims 3
- 238000002347 injection Methods 0.000 abstract description 14
- 239000007924 injection Substances 0.000 abstract description 14
- 239000007788 liquid Substances 0.000 abstract description 13
- 239000003814 drug Substances 0.000 abstract description 10
- 235000011091 sodium acetates Nutrition 0.000 abstract description 7
- 239000003643 water by type Substances 0.000 abstract description 6
- 239000012535 impurity Substances 0.000 abstract description 3
- 206010067482 No adverse event Diseases 0.000 abstract description 2
- ZNRGQMMCGHDTEI-ITGUQSILSA-N tropisetron Chemical compound C1=CC=C2C(C(=O)O[C@H]3C[C@H]4CC[C@@H](C3)N4C)=CNC2=C1 ZNRGQMMCGHDTEI-ITGUQSILSA-N 0.000 description 65
- 238000012360 testing method Methods 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 15
- 239000000463 material Substances 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000013641 positive control Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 206010018910 Haemolysis Diseases 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 230000008588 hemolysis Effects 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 206010070834 Sensitisation Diseases 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 230000008313 sensitization Effects 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 239000010977 jade Substances 0.000 description 3
- 239000002932 luster Substances 0.000 description 3
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- 239000000203 mixture Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical compound C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 3
- 229930004006 tropane Natural products 0.000 description 3
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
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- 238000000386 microscopy Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000013618 particulate matter Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
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- 238000003860 storage Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 229940113081 5 Hydroxytryptamine 3 receptor antagonist Drugs 0.000 description 1
- 102000035037 5-HT3 receptors Human genes 0.000 description 1
- 108091005477 5-HT3 receptors Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
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- 206010015719 Exsanguination Diseases 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 240000007711 Peperomia pellucida Species 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
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- 229950003499 fibrin Drugs 0.000 description 1
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- 230000002070 germicidal effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 1
- 229960003727 granisetron Drugs 0.000 description 1
- 230000035931 haemagglutination Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000007731 hot pressing Methods 0.000 description 1
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- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
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- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
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- 150000003839 salts Chemical class 0.000 description 1
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- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
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- 238000013112 stability test Methods 0.000 description 1
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- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to field of medicaments, more particularly to a kind of Tropisetron HCl parenteral solution and preparation method thereof, the parenteral solution is by weight, including 1.13~28.2 parts of Tropisetron HCls, 3~75 parts of sodium acetates, 1.7~42.5 parts of glacial acetic acid, 1.2~30 parts of sodium chloride, 3000~6000 parts of waters for injection.Preparation method comprises the following steps：(1) Tropisetron HCl is weighed, is added to and accounts in the water for injection of total recipe quantity 60% 95%, sodium acetate, glacial acetic acid, sodium chloride is added, is stirred to dissolve, adds needle-use activated carbon, stirring, with stud coarse filtration carbon removal；(2) add and add to the full amount of water for injection, then filtered successively with 0.60~0.45um, 0.45~0.10um miillpore filter.Tropisetron HCl parenteral solution provided by the present invention is colourless clear liquid, and clarity is high, and dissolubility is good, and impurity has no adverse reaction less, is used conveniently and safely.
Description
Technical field
The present invention relates to field of medicaments, more particularly to a kind of Tropisetron HCl parenteral solution and preparation method thereof.
Background technology
Tropisetron HCl is the 3rd 5-HT3 receptor antagonist listed after Ang Danxi ketone and Granisetron, by
Sandoz companies of Switzerland develop, 1992 first Holland list, trade name Europe must booth (Navoban), be treatment dislike
The heart and the choice drug of vomiting, clinically it is mainly used in preventing and treating nausea and vomiting caused by cancer chemotherapy at present.Tropane
Fine jade is taken charge of compared with other 5-HT3 receptor antagonists, has that side effect is light, low and long action time is reacted between better tolerance, medicine
The characteristics of.
Found through retrieval, Publication No. CN 1969847 application for a patent for invention provides a kind of drug regimen of stabilization
Thing, said composition are the salt by Tropisetron or its pharmaceutical acceptable acid, and pharmaceutically acceptable carrier composition.Especially
Ground is preferred, Tropisetron HCl parenteral solution, its contain osmotic pressure regulator and sodium acetate dosage be 0.36% to 0.18% it is slow
Flushing system.
Publication No. CN102302495A application for a patent for invention discloses a kind of Tropisetron HCl medicine of injection
Compositions, it is made up of Tropisetron HCl, sodium chloride and citric acid, the weight ratio of wherein Tropisetron HCl and citric acid is
1：0.001-5；The preparation method of the pharmaceutical composition：Recipe quantity water for injection 95% is taken, temperature is passed through dioxy at 30-40 DEG C
Change carbon gas to pH value in 3.0-4.0 scopes, add sodium chloride, the citric acid of recipe quantity, after stirring and dissolving；Add recipe quantity
Tropisetron HCl, stirring are complete to dissolving；Medical charcoal is added into above-mentioned solution, after stirring, is placed；Filter, supplement
Water for injection is well mixed to full dose；Initial pH value is measured, according to initial pH value, with 4% sodium hydroxide solution and 10% citron
Acid solution adjusts pH value range in 3.0-4.0；Refined filtration；It is filling；Sterilizing；Lamp inspection；Storage；Get product.
Publication No. CN101732252A application for a patent for invention discloses a kind of Tropisetron hydrochloride suspension injection, by
The component of following parts by weight is made：1 part of Tropisetron HCl, surfactant 2.5-15 parts, antioxidant 0.1-5 parts, additives
5-40 parts, wherein the surfactant is made up of NaTDC and PVP.
It is general to have listed injection Tropisetron dissolubility at present, has added that need after water for injection to rock a few minutes could be completely molten
Solution, influences the convenience used, and the slightly turbid light of solution, influences the security used, and use is also inconvenient.
The content of the invention
It is an object of the invention to provide a kind of Tropisetron HCl parenteral solution and preparation method thereof.
To reach above-mentioned purpose, specifically adopt the following technical scheme that：
A kind of Tropisetron HCl parenteral solution, by weight, including 1.13~28.2 parts of Tropisetron HCls, 3~75 parts
Sodium acetate, 1.7~42.5 parts of glacial acetic acid, 1.2~30 parts of sodium chloride, 3000~6000 parts of (3000ml-6000ml) waters for injection.
Preferably, the Tropisetron HCl parenteral solution, by weight, including 3-11 part Tropisetron HCls, 8-30 parts
Sodium acetate, 5-17 part glacial acetic acid, 3-12 part sodium chloride, 3000-6000 part waters for injection.
It is highly preferred that the Tropisetron HCl parenteral solution, including 5.64 parts of Tropisetron HCls, 14-20 part sodium acetates,
8.6-8.8 part glacial acetic acid, 5-7 part sodium chloride, 3000-6000 part waters for injection.
As embodiments of the present invention, the Tropisetron HCl parenteral solution includes 5.64 parts of Tropisetron HCls, 14-
20 parts of sodium acetates, 8.6-8.8 part glacial acetic acid, 5-7 part sodium chloride, 5000 parts are injected water to, i.e., the concentration of described parenteral solution
For 5ml：5mg, 5mg are in terms of the Tropisetron in Tropisetron HCl.
As the present invention a kind of preferred embodiment, Tropisetron HCl parenteral solution of the invention, by weight, including
5.64 parts of Tropisetron HCls, 15 parts of sodium acetates, 8.5 parts of glacial acetic acid, 6.0 parts of sodium chloride, inject water to 5000 parts.
Tropisetron HCl parenteral solution provided by the present invention is colourless clear liquid, and clarity is high, and dissolubility is good, and miscellaneous
Matter has no adverse reaction less, is used conveniently and safely.
Present invention also offers the preparation method of above-mentioned Tropisetron HCl parenteral solution, following steps are specifically included：
(1) concentrated compounding process：The Tropisetron HCl of recipe quantity is weighed, is added to the injection for accounting for total recipe quantity 60%-95%
With in water, sodium acetate, glacial acetic acid, sodium chloride are added, is stirred to dissolve, obtains mixed solution, added by mass volume ratio and account for mixing
Liquor capacity 0.005-0.06% needle-use activated carbon, 10-40 minutes are stirred at 50~80 DEG C, with stud coarse filtration carbon removal；
(2) it is dilute to match somebody with somebody process：Add and add to the full amount of water for injection, then successively with 0.60~0.45um, 0.45~0.10um's is micro-
Hole filter membrane filtration, embedding are sealed in ampoule, sterilizing, lamp inspection, packaging.
Specifically, the sterilizing described in step (2) is gone out for 110-120 DEG C of pressure sterilizing 20-40 minute or 120-125 DEG C of hot pressing
Bacterium 10-18 minutes.
Preferably, the sterilizing described in step (2) is 115 DEG C of pressure sterilizings 30 minutes or 121 DEG C of pressure sterilizings 15 minutes, this
Sample, which can aid in, reaches that final products are sterile, pyrogen-free target.
The preparation method technique of Tropisetron HCl parenteral solution provided by the invention is simple, easily operated.
Embodiment
Following examples are used to illustrate the present invention, but are not limited to the scope of the present invention.
Embodiment 1
Tropisetron HCl parenteral solution in the present embodiment, including 5.64g Tropisetron HCls, 15g sodium acetates, 8.5g ice vinegar
Acid, 6.0g sodium chloride, adds water to 5000ml.
Embodiment 2-5
Embodiment 2-5 is different from the dosage for differing only in each component of embodiment 1, and specific dosage difference is as follows：
| Component | Embodiment 2 (g) | Embodiment 3 (g) | Embodiment 4 (g) | Embodiment 5 (g) |
| Tropisetron HCl | 5.64 | 5.64 | 5.64 | 5.64 |
| Sodium acetate | 20 | 19 | 18 | 14 |
| Glacial acetic acid | 8.68 | 8.76 | 8.61 | 8.70 |
| Sodium chloride | 5.2 | 5.0 | 6.1 | 6.5 |
| Water for injection | Add water to 5000ml | Add water to 5000ml | Add water to 5000ml | Add water to 5000ml |
Embodiment 6
Tropisetron HCl parenteral solution in the present embodiment, including 1.13g Tropisetron HCls, 3g sodium acetates, 1.7g ice vinegar
Acid, 1.2g sodium chloride, 3000ml waters for injection.
Embodiment 7
Tropisetron HCl parenteral solution in the present embodiment, including 28.2g Tropisetron HCls, 75g sodium acetates, 42.5g ice
Acetic acid, 30g sodium chloride, 6000ml waters for injection.
Embodiment 8
The present embodiment is the preparation method of Tropisetron HCl parenteral solution, is comprised the following steps：
(1) concentrated compounding process：The Tropisetron HCl of recipe quantity is weighed, is added to the injection for accounting for total recipe quantity 60%-95%
With in water, sodium acetate, glacial acetic acid, sodium chloride are added, is stirred to dissolve, obtains mixed solution, added by mass volume ratio and account for mixing
Liquor capacity 0.005-0.06% needle-use activated carbon, stirred 20 minutes at 50~80 DEG C, with stud coarse filtration carbon removal；
(2) it is dilute to match somebody with somebody process：Add and add to the full amount of water for injection, then successively with 0.60~0.45um, 0.45~0.10um's is micro-
The filtration of hole filter membrane, embedding is in 5ml ampoules, sealing, 115 DEG C of pressure sterilizings 30 minutes or 121 DEG C of pressure sterilizings 15 minutes, lamp
Inspection, packaging.
Experimental example 1：
Embodiment 1-5 is prepared with the method for embodiment 8, and sterilize front and rear pH value, clarity and character are as follows：
Experimental example 2：
The Tropisetron HCl parenteral solution product inspection result of the embodiment of the present invention 1：
Experimental example 3：
Drug inspection standard provides：Contain more than 10um in each container of Tropisetron HCl parenteral solution particulate determination
Particulate must not cross 6000, the particulate containing more than 25um must not cross 600.Gained Tropisetron HCl parenteral solution warp of the invention
Testing result is as follows：
| Product | More than 10um particulates (grain) | More than 25um particulates (grain) |
| Embodiment 1 | 1272 | 6 |
| Embodiment 2 | 1186 | 42 |
| Embodiment 3 | 1955 | 26 |
| Embodiment 4 | 1856 | 37 |
| Embodiment 5 | 1921 | 30 |
After testing, inventive samples particulate matter meets drug inspection standard regulation far less than standard requirement.
Pharmaceutical composition coarse filtration stable CN 1969847 uses 0.8um filtering with microporous membrane, and refined filtration uses 0.45um
Filtering with microporous membrane, the present invention use 0.60~0.45um, and 0.45~0.10um miillpore filter filters, and specific coarse filtration is
0.45um, refined filtration 0.22um, it can be seen that the particulate matter particle diameter of the present invention is insoluble less than CN 1969847
Particulate.
Experimental example 4：
We carry out illumination (4000lx) experiment, high temperature (60 DEG C) experiments, low temperature (0~4 to Tropisetron HCl parenteral solution
DEG C) experiment.Table 1 is exposure experiments to light result, and table 2 is 60 DEG C of result of the tests of high temperature, the Tropisetron HCl parenteral solution low temperature 0~4 of table 3
DEG C result of the test, content and the measure about material use high performance liquid chromatography, and measurement result see the table below.
The Tropisetron HCl parenteral solution exposure experiments to light result of table 1
| Time (my god) | Appearance luster | PH value | Relevant material (%) | Clarity | Content (%) |
| 0 | Colourless clear liquid | 4.50 | 0.01 | It is qualified | 103.3 |
| 5 | Colourless clear liquid | 4.46 | 0.01 | It is qualified | 102.1 |
| 10 | Colourless clear liquid | 4.43 | 0.01 | It is qualified | 101.6 |
The 60 DEG C of result of the tests of Tropisetron HCl parenteral solution high temperature of table 2
| Time (my god) | Appearance luster | PH value | Relevant material (%) | Clarity | Content (%) |
| 0 | Colourless clear liquid | 4.50 | 0.01 | It is qualified | 103.3 |
| 5 | Colourless clear liquid | 4.39 | 0.01 | It is qualified | 103.1 |
| 10 | Colourless clear liquid | 4.43 | 0.01 | It is qualified | 102.7 |
0~4 DEG C of result of the test of Tropisetron HCl parenteral solution low temperature of table 3
| Time (my god) | Appearance luster | PH value | Relevant material (%) | Clarity | Content (%) |
| 0 | Colourless clear liquid | 4.50 | 0.01 | It is qualified | 103.3 |
| 5 | Colourless clear liquid | 4.40 | 0.01 | It is qualified | 102.2 |
| 10 | Colourless clear liquid | 4.44 | 0.01 | It is qualified | 102.3 |
Relevant material refers to impurity in table 1- tables 3, refers to the initiation material brought into production process, intermediate, polymerization
Catabolite in body, side reaction product and storage etc., relevant material detection are exactly the detection of impurity, and content refers to
The content of Tropisetron HCl.
Experiment shows, Tropisetron HCl parenteral solution provided by the invention to illumination, 60 DEG C of high temperature and 0~4 DEG C of low temperature not
Sensitivity, it is its character after illumination 10 days, consistent about material, content and 0 day, 60 DEG C of high temperature its character, relevant material after 10 days, contain
Amount is consistent with 0 day.It is 0~4 DEG C of low temperature its character after 10 days, consistent about material, content and 0 day.
CN1969847 stability test tables 1-5 Tropisetron HCl content range value is 96.1-98.8%, the present invention
Content is 101-104% (being shown in Table 1 and table 3), content of the Tropisetron HCl content of the present invention apparently higher than CN1969847；
The relevant material 0.12-0.80% of CN1969847, the relevant material control of the present invention is 0.01%, hence it is evident that less than CN1969847.
Experimental example 5：Tropisetron HCl parenteral solution hypersensitive test
Whether the experiment of this experimental observation Tropisetron HCl injection in Guinea-pigs has allergy effect, the results showed that in this examination
Under the conditions of testing, this product is to animal subject without sensitization.
Experimental method：Healthy guinea pig 18 is taken, Tropisetron HCl parenteral solution group, positive controls are randomly divided into by body weight
And negative control group, every group 6.Dosage：Priming dose：0.5ml/, booster dose：1ml/ is only.Method of administration：Sensitization
For intraperitoneal injection, excite as intravenous injection.Animal subject sensitization：Tropisetron HCl note is injected intraperitoneally in each group cavy next day respectively
Liquid, physiological saline, ovalbumin are penetrated, 0.5ml/ only, is total to sensitization three times.Attack：Every group of animal is divided into 2 groups, each 3.One group
14 days intravenous injection administration 1ml/ only (inject speed as 40 seconds) and attacked after first administration, and another group the 21st after first administration
Its intravenous injection administration 1ml/ is only attacked.Observation index：In attack be administered after in 15 minutes observe animal whether there is perpendicular hair, sneeze,
The allergic reaction such as retch, cough, expiratory dyspnea, rale, twitch, collapse or death.
Experimental result：Attack result is feminine gender to Tropisetron HCl parenteral solution twice, and positive controls can make it is tested
Animal occurs grabbing the performances such as nose, perpendicular hair, expiratory dyspnea, spasm shock death.Result of the test shows Tropisetron HCl parenteral solution
Hypersensitive test is feminine gender.
Experimental example 6：Tropisetron HCl parenteral solution hemolytic test
This Germicidal efficacy haemocylolysis of the Tropisetron HCl parenteral solution to family's rabbit erythrocyte, the results showed that hydrochloric acid tropane
Fine jade parenteral solution is taken charge of to red blood cell without obvious hemolysis in vitro and cohesion.
Experimental method：Experiment sets blank control group, positive controls and test group.Rabbit blood is taken by artery in ear during experiment
10ml, put in beaker and remove fibrin with fine glass rod, then take 5ml to move into 10ml graduated centrifuge tubes, add physiological saline
5ml, 3000 turns, 5 minutes are carried out after mixing and is centrifuged, removes supernatant, then add physiological saline 5ml, mixed centrifugation, wash three repeatedly
It is secondary, to supernatant water white transparency.Gained red blood cell is pressed into volume, with suspension of the normal saline dilution into 2%.7, test tube is taken,
Different solutions are separately added into, the 6th pipe is not added with being made blank control by test product, and the 7th pipe is still not added with by test product, and physiology is replaced with distilled water
Salt solution, make positive control.Each pipe is gently shaken up, 4 hours are incubated in 37 DEG C of water-baths.Start to see every 15 minutes after insulation
Examine once, after 1 hour, every observation in 1 hour once, observe 4 hours.Each pipe haemolysis situation is visually observed, is shown if necessary
Micro mirror is examined.
Experimental result：There is haemolysis in 1 hour in positive control pipe, adds by test product Tropisetron HCl parenteral solution
1~5 pipe is also normal without hemagglutination, microscope inspection red blood cell profile without haemolysis.Repeat experiment once, knot
Fruit is identical.Show Tropisetron HCl parenteral solution to red blood cell without haemolysis and cause agglutination.
Experimental example 7：Tropisetron HCl parenteral solution vascular stimulation is tested
This experimental observation Tropisetron HCl parenteral solution is for three days on end to the excitant of animal blood vessels, the results showed that this product exists
Rabbit ear edge is acted on without obvious stimulation under the experimental condition.
Experimental method：Take health, ear edge not damaged rabbit 8, be randomly divided into Tropisetron HCl parenteral solution medication group and
1% glacial acetic acid positive controls, every group 4.Respectively at right side auricular vein instillation each group solution 10ml, injection speed during experiment
2ml/min.It is daily to instil once, for three days on end.Left side auricular vein instillation normal saline is as negative control.Observation refers to
Mark：Visually observe within 0 to 24 hour after administration the red and swollen situation of the local vein blood vessel surrounding tissue of administration, last dose 24 hours
Afterwards by animal sacrificed by exsanguination, clip ear edge, is fixed with 10% formaldehyde at injection site proximal part 1.5cm to 3cm, conventional
Histotomy, observation whether there is thrombosis, whether there is endothelial injuries and other pathological changes.
Experimental result：Visually observe：1% glacial acetic acid positive controls visible tissue swelling, blood vessel dilatation, hydrochloric acid tropane department
Fine jade parenteral solution group has no the stimulate the reactions such as obvious blood vessel dilatation, redness.Pathological examination：Negative control group：Censorship sample structure
Normally, auricular vein is unexpanded, and vascular endothelial cell, which has no, to be increased and arrangement disorder, and vascular wall is without thickening and the pathology shape such as inflammation
State changes.The same negative control group of medication group microscopy auricular vein form, change without obvious pathomorphism.Positive controls：Microscopy
Visible vessels are expanded, and intracavitary has extravasated blood, pipe week cell infiltration, tissue has oedema.Experiment results proved Tropisetron HCl is noted
It is nonirritant to blood vessel to penetrate liquid.
Although above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements, belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (3)
- A kind of 1. Tropisetron HCl parenteral solution, it is characterised in that by weight, including 5.64 parts of Tropisetron HCls, 14-20 Part sodium acetate, 8.6-8.8 part glacial acetic acid, 5-7 part sodium chloride, injects water to 5000 parts；The preparation method of the Tropisetron HCl parenteral solution comprises the following steps：(1) concentrated compounding process：Tropisetron HCl is weighed, is added to and accounts in total water for injection 60%-95% water, adds acetic acid Sodium, glacial acetic acid, sodium chloride, stirring and dissolving, obtain mixed solution, are added by mass volume ratio and account for mixed liquor volume 0.005- 0.06% needle-use activated carbon, 10-40 minutes are stirred at 50~80 DEG C, with stud coarse filtration carbon removal；(2) it is dilute to match somebody with somebody process：Add and add to the full amount of water for injection, then filtered successively with 0.60~0.45um, 0.45~0.10um micropore Membrane filtration mistake, embedding are sealed in ampoule, sterilizing, lamp inspection, packaging；Described sterilizing is 110-120 DEG C of pressure sterilizing 20-40 minute or 120-125 DEG C of pressure sterilizing 10-18 minute.
- A kind of 2. Tropisetron HCl parenteral solution, it is characterised in that by weight, including 5.64 parts of Tropisetron HCls, 15 parts Sodium acetate, 8.5 parts of glacial acetic acid, 6.0 parts of sodium chloride, inject water to 5000 parts；The preparation method of the Tropisetron HCl parenteral solution comprises the following steps：(1) concentrated compounding process：Tropisetron HCl is weighed, is added to and accounts in total water for injection 60%-95% water, adds acetic acid Sodium, glacial acetic acid, sodium chloride, stirring and dissolving, obtain mixed solution, are added by mass volume ratio and account for mixed liquor volume 0.005- 0.06% needle-use activated carbon, 10-40 minutes are stirred at 50~80 DEG C, with stud coarse filtration carbon removal；(2) it is dilute to match somebody with somebody process：Add and add to the full amount of water for injection, then filtered successively with 0.60~0.45um, 0.45~0.10um micropore Membrane filtration mistake, embedding are sealed in ampoule, sterilizing, lamp inspection, packaging；Described sterilizing is 110-120 DEG C of pressure sterilizing 20-40 minute or 120-125 DEG C of pressure sterilizing 10-18 minute.
- 3. the preparation method of the Tropisetron HCl parenteral solution described in claim 1 or 2, it is characterised in that comprise the following steps：(1) concentrated compounding process：Tropisetron HCl is weighed, is added to and accounts in total water for injection 60%-95% water, adds acetic acid Sodium, glacial acetic acid, sodium chloride, stirring and dissolving, obtain mixed solution, are added by mass volume ratio and account for mixed liquor volume 0.005- 0.06% needle-use activated carbon, 10-40 minutes are stirred at 50~80 DEG C, with stud coarse filtration carbon removal；(2) it is dilute to match somebody with somebody process：Add and add to the full amount of water for injection, then filtered successively with 0.60~0.45um, 0.45~0.10um micropore Membrane filtration mistake, embedding are sealed in ampoule, sterilizing, lamp inspection, packaging；Sterilizing described in step (2) is 110-120 DEG C of pressure sterilizing 20-40 minute or 120-125 DEG C of 10-18 points of pressure sterilizing Clock.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1969847A (en) * | 2006-12-11 | 2007-05-30 | 重庆人本药物研究院 | Pharmaceutical composition |
| CN102274194A (en) * | 2011-06-16 | 2011-12-14 | 罗诚 | Pharmaceutical composition containing tropisetron compound and preparation method thereof |
| CN102302495A (en) * | 2011-07-07 | 2012-01-04 | 天津市汉康医药生物技术有限公司 | Tropisetron hydrochloride medicament composition for injection |
| CN102697714A (en) * | 2012-06-25 | 2012-10-03 | 福建天泉药业股份有限公司 | Levofloxacin hydrochloride injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1969847A (en) * | 2006-12-11 | 2007-05-30 | 重庆人本药物研究院 | Pharmaceutical composition |
| CN102274194A (en) * | 2011-06-16 | 2011-12-14 | 罗诚 | Pharmaceutical composition containing tropisetron compound and preparation method thereof |
| CN102302495A (en) * | 2011-07-07 | 2012-01-04 | 天津市汉康医药生物技术有限公司 | Tropisetron hydrochloride medicament composition for injection |
| CN102697714A (en) * | 2012-06-25 | 2012-10-03 | 福建天泉药业股份有限公司 | Levofloxacin hydrochloride injection and preparation method thereof |
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