CN101810627B - Compound sulfamonomethoxine/compound sulfamonomethoxine sodium injection and preparation method - Google Patents
Compound sulfamonomethoxine/compound sulfamonomethoxine sodium injection and preparation method Download PDFInfo
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- CN101810627B CN101810627B CN2009102275065A CN200910227506A CN101810627B CN 101810627 B CN101810627 B CN 101810627B CN 2009102275065 A CN2009102275065 A CN 2009102275065A CN 200910227506 A CN200910227506 A CN 200910227506A CN 101810627 B CN101810627 B CN 101810627B
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- WMPXPUYPYQKQCX-UHFFFAOYSA-N Sulfamonomethoxine Chemical compound C1=NC(OC)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 WMPXPUYPYQKQCX-UHFFFAOYSA-N 0.000 title claims abstract description 77
- 229950003874 sulfamonomethoxine Drugs 0.000 title claims abstract description 77
- 238000002347 injection Methods 0.000 title claims abstract description 76
- 239000007924 injection Substances 0.000 title claims abstract description 76
- IZJAOWYNDLDRKM-UHFFFAOYSA-N sodium;(4-aminophenyl)sulfonyl-(6-methoxypyrimidin-4-yl)azanide Chemical compound [Na+].C1=NC(OC)=CC([N-]S(=O)(=O)C=2C=CC(N)=CC=2)=N1 IZJAOWYNDLDRKM-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 150000001875 compounds Chemical class 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims description 21
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229960001082 trimethoprim Drugs 0.000 claims abstract description 25
- 229960001193 diclofenac sodium Drugs 0.000 claims abstract description 21
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000008215 water for injection Substances 0.000 claims abstract description 17
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 8
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
- 239000007788 liquid Substances 0.000 claims description 40
- 239000002131 composite material Substances 0.000 claims description 33
- 238000003756 stirring Methods 0.000 claims description 32
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 21
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 18
- 239000000706 filtrate Substances 0.000 claims description 16
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 16
- 238000005374 membrane filtration Methods 0.000 claims description 14
- 235000010265 sodium sulphite Nutrition 0.000 claims description 9
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical group [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 9
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 9
- 238000011049 filling Methods 0.000 claims description 8
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 8
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- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 5
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- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 4
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- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
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- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
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- 150000003180 prostaglandins Chemical class 0.000 description 2
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- -1 pyrimidine nucleic acid Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- 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 1
- 208000006820 Arthralgia Diseases 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
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- 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
- 206010065390 Inflammatory pain Diseases 0.000 description 1
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- 108010022394 Threonine synthase Proteins 0.000 description 1
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- 238000010521 absorption reaction Methods 0.000 description 1
- IZNMWVDUFGUSMX-UHFFFAOYSA-N acetic acid;acetonitrile;methanol Chemical compound OC.CC#N.CC(O)=O IZNMWVDUFGUSMX-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
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- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a compound sulfamonomethoxine or compound sulfamonomethoxine sodium injection which is prepared from main components and auxilary components, wherein the main components comprise 5-20 parts by weight of sulfamonomethoxine/sulfamonomethoxine sodium, 1-4 parts by weight of diclofenac sodium and 1-4 parts by weight of trimethoprim and the auxilary components comprise 0.2-0.4 part by weight of antioxidant, 40-70 parts by weight of organic solvent, 0.2-1 part by weight of regulating reagent and 10-20 parts by weight of water for injection. The injection prepared by the invention can provide effective treatment on secondary infection and mixed infection of streptococcicosis, toxoplasmosis, eperythrozoonosis, colibacillosis, asthma and other diseases, has obvious effect if applied for a long term, strong effect enhanced by several times or dozens of times, hardly generates drug resistance and has the advantages of less consumption, less application times, little irritation and quick treatment effect, can treat both symptoms and root causes, save production cost, improve product additional value and reduce toxic or side effects caused by mismatching of medicaments during treatment.
Description
Technical field
The present invention relates to the veterinary drug preparation field, particularly relate to a kind of compound sulfamonomethoxine daimeton injection or composite sulfamonomethoxine sodium injection and preparation method.
Background technology
Sulfa drugs is a class medicine relatively more commonly used, sulfamonomethoxine (Sulfamonomethoxine, write a Chinese character in simplified form SMM) be the strongest novel sulfonamides of inside and outside antibacterial action, similar para-amino benzoic acid (PABA) on its structure, can act on the intravital dihydrofolate synthetase of antibacterial with PABA competitiveness, thereby blocking-up PABA is as the process of the synthetic required folic acid of antibacterial of raw material, reduced amount with metabolic tetrahydrofolic acid, tetrahydrofolic acid is the essential material of antibacterial synthetic DNA and thymus pyrimidine nucleic acid, therefore has the growth and breeding that suppresses antibacterial.Most of gram positive bacterias and negative bacterium are all had strong inhibitory action, and it is slower that antibacterial produces drug resistance to this medicine.SMM is mainly used in the caused various diseases of sensitive organism, and to pig toxoplasmosis, bowel oedema disease, fowl, rabbit coccidiosis also have curative effect preferably.This product administration post-absorption is good, the blood level height, and the acetylation rate is low, and acetylate dissolubility in urine is big, is difficult for taking place crystalluria.Hold time Babalus bubalis L. 24 hours of effective blood drug concentration, pig 5.8 hours, goat 7 hours, sheep 2 hours.Have that has a broad antifungal spectrum, infiltration rate are fast, stability by force, advantage such as not perishable, wide material sources, price are low.
Trimethoprim (Trimethoprim writes a Chinese character in simplified form TMP), effective to most gram positive bacterias and negative bacterium.Use the very easy generation drug resistance of antibacterial separately.Share with sulphonamides, can make the folic acid metabolism of antibacterial be subjected to double blocking, promptly sulphonamides suppresses dihydrofolate synthetase, suppresses the synthetic of dihydrofoilic acid; And TMP suppresses dihydrofolate reductase, makes dihydrofoilic acid can not be reduced to tetrahydrofolic acid and consequently hinders the synthetic of ribonucleic acid, suppresses the growth of antibacterial, makes the bacteriostasis of sulphonamides can strengthen several times to tens times.And can reduce the appearance of Resistant strain.Clinical main share in the infection for the treatment of respiratory tract, urinary tract and soft tissue, as bronchitis, pneumonia, bacillary dysentery, meningitis, otitis media, pyelonephritis, enteritis and typhoid fever etc. with sulphonamides.
Diclofenac sodium (Diclofenac Sodium) is a kind of non-steroidal anti-inflammatory analgesics that is derived from the phenylacetic acid class, is that effect is stronger a kind of in this type of medicine, and its mechanism of action is for suppressing the Cycloxygenase activity, thereby the blocking-up arachidonic acid transforms prostaglandin.Simultaneously, it also can promote arachidonic acid to combine with triglyceride (triacylglycerol), reduces the arachidonic acid concentration of endocellular liberation, and suppresses the synthetic of leukotriene indirectly, and the synthetic inhibitory action of prostaglandin is better than aspirin and indomethacin etc.Diclofenac sodium is strong cyclooxygenase-2 inhibitors, has antiinflammatory, antipyretic effect.For various arthralgia, soft tissue rheumatism pain, tenosynovitis, bursitis and inflammatory heating good effect is arranged.
The raw material that " Chinese veterinary drug allusion quotation " one one of version in 2005 has been recorded has: sulfamonomethoxine, sulfamonomethoxine sodium, trimethoprim, preparation has: sulfamonomethoxine sheet, sulfamonomethoxine sodium injection.These medicine directeds toward bacteria, protozoacide control have certain effect, yet, current owing to antibacterial, protozoacide infection present mixed infection or secondary infection more, as mixed infections such as streptococcicosis and toxoplasmosis, eperythrozoonosises, colibacillosis and asthma mixed infection, and the infection of these diseases shows as clinically substantially that infectiousness is strong, hyperpyrexia and inflammation, independent therapeutic effect with the sulfamonomethoxine sodium injection is relatively poor, twice of injection in common a day, zest is stronger, and injection volume is big.
Summary of the invention
The object of the present invention is to provide that a kind of use amount is little, the medication number of times is few, zest is little, the drug effect performance is fast, the compound sulfamonomethoxine daimeton injection or the composite sulfamonomethoxine sodium injection for the treatment of both the principal and secondary aspects of a disease, the present invention also provides the preparation method of above-mentioned injection.
For achieving the above object, the present invention can take following technical proposals:
Composite sulfamonomethoxine of the present invention or composite sulfamonomethoxine sodium injection, it is formulated according to the following weight parts proportioning by principal agent sulfamonomethoxine or sulfamonomethoxine sodium, diclofenac sodium, trimethoprim and adjuvant antioxidant, organic solvent, adjusting reagent, water for injection:
Described organic solvent is alpha-pyrrolidone, propylene glycol and benzyl alcohol, alpha-pyrrolidone by volume between the three: propylene glycol: benzyl alcohol=5～10: 30～50: 5～10 mix and promptly get required mixing organic solvent.
Described antioxidant is sodium thiosulfate or sodium sulfite.
Described adjusting reagent is sodium hydroxide or hydrochloric acid, is used to regulate the pH value of injection of the present invention between 9.5-10.5.During actual fabrication, according to circumstances regulate, the pH value height goes beyond the scope, and available hydrochloric acid is regulated, and pH value is lower than this scope, and the available hydrogen sodium oxide is regulated.
The preparation method of composite sulfamonomethoxine of the present invention or composite sulfamonomethoxine sodium injection, it comprises the steps:
The first step: get water for injection and be heated to 50-60 ℃, add antioxidant respectively, regulate reagent and diclofenac sodium, stir and make its whole dissolvings, be prepared into A liquid, standby;
Second step: get organic solvent and be heated to 60-70 ℃, add sulfamonomethoxine or sulfamonomethoxine sodium, trimethoprim respectively, stir and make its whole dissolvings, be prepared into B liquid;
The 3rd step: with stirring in the above-mentioned A liquid adding B liquid, continue to stir 30 minutes, behind organic membrane filtration, obtain filtrate;
The 4th step: with above-mentioned filtrate with filling and sealing machine respectively fill in bottle,, can obtain the compound sulfamonomethoxine daimeton injection or the composite sulfamonomethoxine sodium injection of colourless or faint yellow clear liquid through 115 ℃, pressure 0.2MPa sterilization 30 minutes.
During fill, can fill in cillin bottle, ampoule bottle, vial, loading amount comprises 5ml, 10ml, 20ml, 50ml, 100ml, 200ml, 250ml, 500ml etc.
The invention has the advantages that above-mentioned injection can provide effective treatment at the secondary infection and the mixed infection of diseases such as streptococcicosis, toxoplasmosis, eperythrozoonosis, colibacillosis, asthma.
One, the advantage of injection of the present invention is in particular in:
1. the experiment of above-mentioned injection shows: its in vivo valid density hold time for 72.07h ± 9.51h, and common sulfamonomethoxine daimeton injection only is 48.72h ± 10.83h, long-acting effect obviously is better than common compound sulfamonomethoxine daimeton injection, thus can think this injection can medication in three days once.
2. sulfamonomethoxine is a broad spectrum antibiotic, trimethoprim is an antibacterial, when the two uses separately respectively, only pathogenic microorganism is had inhibitory action, do not have killing action, antibacterial easily produces drug resistance, and the two unites use, drug effect strengthens several times to tens times, presents antibacterial is produced killing action, also is difficult for producing drug resistance.
3. diclofenac sodium is a kind of antipyretic-antalgic, anti-inflammation drugs, usually disease is in generating process,, hyperpyrexia depressed, inflammatory pain etc. with spirit, the present invention has specially good effect to this type of symptom, usually have multiple effects such as anti-inflammation, antipyretic-antalgic, have symptomatic treatment and etiological treatment simultaneously at disease.
4. the present invention is the new medicinal preparation of triple effect unification, and use amount is little, the medication number of times is few, zest is little, the drug effect performance is fast, have the characteristics for the treatment of both the principal and secondary aspects of a disease.
5. this injection has been saved production cost with the several drugs use that is mixed, and has improved added value of product.The toxic and side effects that has occurred owing to the medicine mismate when having reduced treatment.
Two, adopt the extracorporeal bacteria inhibitor test of the composite sulfamonomethoxine sodium injection of the present invention's preparation
1.1 medicine and bacterial strain:
The composite sulfamonomethoxine sodium injection of the present invention's preparation, the laboratory self-control
The trimethoprim injection, the laboratory self-control
Escherichia coli (standard) are purchased in China Veterinary Drugs Supervisory Inst.
1.2 method:
Adopt medicines such as micro-broth dilution method composite sulfamonomethoxine sodium injection, sulfamonomethoxine sodium injection, trimethoprim injection to colibacillary minimum inhibitory concentration (MIC).
The antibacterial culturing plate is put 37 ℃ and was cultivated observed result 24 hours.With control wells relatively, find out with ocular estimate and to begin to become clarifying the 1st hole, the concentration in this hole is minimal inhibitory concentration (MIC).
1.3 result
Colibacillary MIC is respectively: (seeing the following form)
| Medicine | MIC |
| The composite sulfamonomethoxine sodium injection | 2 19 |
| The sulfamonomethoxine sodium injection | 2 16 |
| The trimethoprim injection | 2 6 |
Can find out that from MIC result's statistics of last table the composite sulfamonomethoxine sodium injection is significantly higher than sulfamonomethoxine sodium injection and trimethoprim injection (p＜0.05).
Three, compound sulfamonomethoxine daimeton injection is in the intravital pharmacokinetics research of pig
1, materials and methods
1.1 medicine
Compound sulfamonomethoxine daimeton injection: adopt the present invention's preparation.
Sulfamonomethoxine daimeton injection: Zhengzhou animal pharmaceutical factory produces.
The sulfamonomethoxine standard substance: content is 99.7%, and lot number is 070628, is provided by China Veterinery Drug Inspection Office.
The sulfamonomethoxine crude drug: content is 95.5%, and lot number is 070301, and Huangyan, Zhejiang animal pharmaceutical factory produces.
1.2 test solution method
The HPLC method.Mobile phase: glacial acetic acid-acetonitrile-methanol solution.
1.3 experimental animal
12 of health pig, body weight 25.38kg ± 4.05kg is available from pig farm, Zhenyang, Henan.
1.4 administration and blood specimen collection
12 pigs are divided into 2 groups at random, use compound sulfamonomethoxine daimeton injection for the 1st group, use the sulfamonomethoxine daimeton injection injection, carry out intramuscular injection by 0.4mL/kg dosage respectively for the 2nd group.
Adopt the primary blank blood sample before the administration, after the administration respectively at the 0.25th, 0.50,0.75,1.00,2.00,3.00,5.00,9.00,12.00,24.00,36.00,48.00,72.00,96.00,108.00,120.00h is from the vena cava anterior 5mL that takes a blood sample, place the centrifuge tube that contains heparin, mixing, the centrifugal 10min of 3000r/min, separated plasma carries out HPLC and measures.
1.5 date processing
Adopt " MCPKP " pharmacokinetics calculation procedure that data are handled.
2, result
The result shows: the elimination half-life of two kinds of injection, (t1/2 β) was respectively 20.20h ± 5.31h and 9.81h ± 1.03h; (tmax) is respectively 1.03h ± 0.17h and 2.16h ± 0.35h during the peak; Peak concentration (Cmax) is respectively 22.30 μ g/mL ± 2.09 μ g/mL and 15.96 μ g/mL ± 2.36 μ g/mL; Area under curve (AUC) is respectively 533.58 μ g/ (mLh) ± 30.76 μ g/ (mLh) and 199.91 μ g/ (mLh) ± 11.31 μ g/ (mLh); The valid density tcp (ther) that holds time is respectively 72.07h ± 9.51h and 48.72h ± 10.83h, and minimum active drug concentration is 0.5 μ g/mL in the blood.
3, discuss
This result of the test shows, the compound sulfamonomethoxine daimeton injection that adopts the present invention's preparation with the 0.2mL/kg intramuscular injection after, the eliminations half-life is 20.20h ± 5.31h, significantly is longer than for oral administration and normal injection agent.
The pharmacokinetics analysis result shows that compound sulfamonomethoxine daimeton injection and sulfamonomethoxine daimeton injection meet two-compartment model in the intravital pharmacokinetics of pig.When eliminating half-life, peak concentration, peak, valid density is held time and parameter such as area under curve on there were significant differences (P＜0.05).
The blood drug level testing result shows that the valid density of compound sulfamonomethoxine daimeton injection of the present invention is held time for 72.07h ± 9.51h, and the injection of common sulfamonomethoxine daimeton injection only is 48.72h ± 10.83h; The former half-life is 2 times of the latter.This illustrates that compound sulfamonomethoxine daimeton injection of the present invention is slower than common sulfamonomethoxine daimeton injection elimination, and the time of keeping blood drug level in vivo is long, and long-acting effect obviously is better than common sulfamonomethoxine daimeton injection.
Four, the composite sulfamonomethoxine sodium injection is at the veterinary clinic effect
1. material
1.1 medicine
The composite sulfamonomethoxine sodium injection adopts the present invention's preparation
1.2 case source: the technical staff in Zhengzhou, areas such as Kaifeng, Zhoukou City gather clinical natural occurrence case, are respectively pig streptococcicosis 638 examples, toxoplasmosis 350 examples, chicken coccidiosis 2019 examples, rabbit coccidiosis 425 examples, sick 305 examples of yellow and white dysentery of piglet, sick 2250 examples of chicken leucocyte protozoon, baby swine paratyphoid 380 examples, Mammitis of cattle 130 examples, sheep clostridium enteritis 242 examples.
1.3 case diagnosis: according to epidemiology, clinical symptoms, pathological change, laboratory is made a definite diagnosis with natural cases.Analysis-by-synthesis is made a definite diagnosis.
1.4 implementation process: carry out case by the technical staff of this seminar by test requirements document and select and implement to treat, and log.
1.5 the result judges
With natural cases according to dosage with the administration course of treatment, observe in the week, pay a return visit the also record state of an illness.
Cure: the complete obiteration of 2-3 future trouble poultry of medication disease, spirit, body temperature, appetite recover normal, and urine feces is also normal.
Effectively: 2-3 future trouble poultry of medication disease disappears substantially, and spirit, body temperature, appetite make moderate progress, and urine feces is also normal.
Invalid: 2-3 future trouble poultry of medication disease does not disappear, and sb.'s illness took a turn for the worse or death, and urine feces is also normal.
2. result
Composite sulfamonomethoxine sodium injection clinical therapeutic efficacy statistical table
The composite sulfamonomethoxine sodium injection has good therapeutic effect as can be seen from the above table, to the effective percentage of diseases such as toxoplasmosis, streptococcicosis, coccidiosis, leucocyte protozoon disease, clostridium enteritis, baby swine paratyphoid more than 95%, effective percentage such as yellow and white dysentery of piglet, Mammitis of cattle are reached more than 92%, and cure rate is all more than 90%.
The specific embodiment
Embodiment 1:
Composite sulfamonomethoxine sodium injection of the present invention, it is to be formed by following feedstock production:
One: prescription
Sulfamonomethoxine sodium 5g, trimethoprim 1g, diclofenac sodium 1g, sodium thiosulfate 0.2g, alpha-pyrrolidone 5ml, benzyl alcohol 5ml, propylene glycol 30ml, sodium hydroxide 0.3g, water for injection 10ml;
Two: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds sodium thiosulfate, sodium hydroxide, diclofenac sodium respectively, stirs and makes its whole dissolvings, and it is standby to be prepared into A liquid;
Second step, get alpha-pyrrolidone, propylene glycol, benzyl alcohol, be heated to 60-70 ℃, add sulfamonomethoxine sodium, trimethoprim respectively, stir and make its whole dissolvings, be prepared into B liquid;
The 3rd step, with stirring in the A liquid adding B liquid, continue to stir 30 minutes, be 0.45 micron organic membrane filtration with diameter earlier, the reuse diameter is 0.22 micron organic membrane filtration, obtains filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the composite sulfamonomethoxine sodium injection of colourless or faint yellow clear liquid.
Embodiment 2:
Compound sulfamonomethoxine daimeton injection of the present invention, it is to be formed by following feedstock production:
One: prescription
Sulfamonomethoxine 5g, trimethoprim 1g, diclofenac sodium 1g, sodium sulfite 0.2g, alpha-pyrrolidone 5ml, benzyl alcohol 5ml, propylene glycol 30ml, sodium hydroxide 0.5g, water for injection 10ml;
Two: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds sodium sulfite, sodium hydroxide, diclofenac sodium respectively, stirs and makes its whole dissolvings, and it is standby to be prepared into A liquid;
Second step, get alpha-pyrrolidone, propylene glycol, benzyl alcohol, be heated to 60-70 ℃, add sulfamonomethoxine, trimethoprim respectively, stir and make its whole dissolvings, be prepared into B liquid;
The 3rd step, with stirring in the A liquid adding B liquid, continue to stir 30 minutes, be 0.45 micron organic membrane filtration with diameter earlier, the reuse diameter is 0.22 micron organic membrane filtration, obtains filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the compound sulfamonomethoxine daimeton injection of colourless or faint yellow clear liquid.
Embodiment 3:
Composite sulfamonomethoxine sodium injection of the present invention, it is to be formed by following feedstock production:
One: prescription
Sulfamonomethoxine sodium 10g, trimethoprim 2g, diclofenac sodium 2g, sodium thiosulfate 0.2g, alpha-pyrrolidone 10ml, benzyl alcohol 8ml, propylene glycol 40ml, sodium hydroxide 0.35g, water for injection 15ml;
Two: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds sodium thiosulfate, sodium hydroxide, diclofenac sodium respectively, stirs and makes its whole dissolvings, and it is standby to be prepared into A liquid;
Second step, get alpha-pyrrolidone, propylene glycol, benzyl alcohol, be heated to 60-70 ℃, add sulfamonomethoxine sodium, trimethoprim respectively, stir and make its whole dissolvings, be prepared into B liquid;
The 3rd step, with stirring in the A liquid adding B liquid, continue to stir 30 minutes, be 0.45 micron organic membrane filtration with diameter earlier, the reuse diameter is 0.22 micron organic membrane filtration, obtains filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the composite sulfamonomethoxine sodium injection of colourless or faint yellow clear liquid.
Embodiment 4:
Compound sulfamonomethoxine daimeton injection of the present invention, it is to be formed by following feedstock production:
One: prescription
Sulfamonomethoxine 10g, trimethoprim 2g, diclofenac sodium 2g, sodium sulfite 0.2g, alpha-pyrrolidone 10ml, benzyl alcohol 8ml, propylene glycol 30ml, sodium hydroxide 0.8g, water for injection 15ml;
Two: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds sodium sulfite, sodium hydroxide, diclofenac sodium respectively, stirs and makes its whole dissolvings, and it is standby to be prepared into A liquid;
Second step, get alpha-pyrrolidone, propylene glycol, benzyl alcohol, be heated to 60-70 ℃, add sulfamonomethoxine, trimethoprim respectively, stir and make its whole dissolvings, be prepared into B liquid;
The 3rd step, with stirring in the A liquid adding B liquid, continue to stir 30 minutes, be 0.45 micron organic membrane filtration with diameter earlier, the reuse diameter is 0.22 micron organic membrane filtration, obtains filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the compound sulfamonomethoxine daimeton injection of colourless or faint yellow clear liquid.
Embodiment 5:
Composite sulfamonomethoxine sodium injection of the present invention, it is to be formed by following feedstock production:
One: prescription
Sulfamonomethoxine sodium 20g, trimethoprim 4g, diclofenac sodium 4g, sodium thiosulfate 0.4g, alpha-pyrrolidone 10ml, methanol 10ml, propylene glycol 45ml, sodium hydroxide 0.9g, water for injection 20ml;
Two: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds sodium thiosulfate, sodium hydroxide, diclofenac sodium respectively, stirs and makes its whole dissolvings, and it is standby to be prepared into A liquid;
Second step, get alpha-pyrrolidone, propylene glycol, benzyl alcohol, be heated to 60-70 ℃, add sulfamonomethoxine sodium, trimethoprim respectively, stir and make its whole dissolvings, be prepared into B liquid;
The 3rd step, with stirring in the A liquid adding B liquid, continue to stir 30 minutes, be 0.45 micron organic membrane filtration with diameter earlier, the reuse diameter is 0.22 micron organic membrane filtration, obtains filtrate;
In the 4th step, fill is in bottle respectively with filling and sealing machine with above-mentioned filtrate, and through 115 ℃, pressure 0.2Mpa sterilized 30 minutes, can obtain the composite sulfamonomethoxine sodium injection of colourless or faint yellow clear liquid.
Embodiment 6:
Compound sulfamonomethoxine daimeton injection of the present invention, it is to be formed by following feedstock production:
One: prescription
Sulfamonomethoxine 20g, trimethoprim 4g, diclofenac sodium 4g, sodium sulfite 0.4g, alpha-pyrrolidone 10ml, benzyl alcohol 10ml, propylene glycol 50ml, sodium hydroxide 1g, water for injection 20ml;
Two: preparation method
The first step is got water for injection and is heated to 50-60 ℃, adds sodium sulfite, sodium hydroxide, diclofenac sodium respectively, stirs and makes its whole dissolvings, and is for A liquid, standby;
Second step, get alpha-pyrrolidone, propylene glycol, benzyl alcohol, be heated to 60-70 ℃, add sulfamonomethoxine, trimethoprim respectively, stir and make its whole dissolvings, be B liquid;
The 3rd step, with stirring in the A liquid adding B liquid, continue to stir 30 minutes, be 0.45 micron organic membrane filtration with diameter earlier, the reuse diameter is 0.22 micron organic membrane filtration, obtains filtrate;
The 4th step, use the filling and sealing machine fill in bottle above-mentioned filtrate, through 115 ℃, pressure 0.2MPa sterilized 30 minutes, can obtain the compound sulfamonomethoxine daimeton injection of colourless or faint yellow clear liquid.
More than each embodiment further specify of the present invention, in the practice process, not only be confined to above opereating specification, can replace mutually as antioxidant sodium thiosulfate and sodium sulfite, the consumption of organic solvent can according to circumstances be adjusted,, adjunct ingredient former with shown in the content of weight portion proportioning of the present invention each is the composite sulfamonomethoxine or the composite sulfamonomethoxine sodium injection of basis preparation, all should calculate to be the scope of the invention.
Claims (3)
1. composite sulfamonomethoxine or composite sulfamonomethoxine sodium injection is characterized in that: it is formulated according to the following weight parts proportioning by principal agent sulfamonomethoxine or sulfamonomethoxine sodium, diclofenac sodium, trimethoprim and adjuvant antioxidant, organic solvent, adjusting reagent, water for injection:
Described organic solvent is alpha-pyrrolidone, propylene glycol and benzyl alcohol, alpha-pyrrolidone by volume between the three: propylene glycol: benzyl alcohol=5～10: 30～50: 5～10 mix and promptly get required mixing organic solvent;
Described adjusting reagent is sodium hydroxide.
2. composite sulfamonomethoxine according to claim 1 or composite sulfamonomethoxine sodium injection is characterized in that: described antioxidant is sodium thiosulfate or sodium sulfite.
3. the preparation method of composite sulfamonomethoxine according to claim 1 or composite sulfamonomethoxine sodium injection, it is characterized in that: it comprises the steps:
The first step: get water for injection and be heated to 50-60 ℃, add antioxidant respectively, regulate reagent and diclofenac sodium, stir and make its whole dissolvings, it is standby to be prepared into A liquid;
Second step: get organic solvent and be heated to 60-70 ℃, add sulfamonomethoxine or sulfamonomethoxine sodium, trimethoprim respectively, stir and make its whole dissolvings, be prepared into B liquid;
The 3rd step: with stirring in the above-mentioned A liquid adding B liquid, continue to stir 30 minutes, behind organic membrane filtration, obtain filtrate;
The 4th step: with above-mentioned filtrate with filling and sealing machine respectively fill in bottle,, can obtain the compound sulfamonomethoxine daimeton injection or the composite sulfamonomethoxine sodium injection of colourless or faint yellow clear liquid through 115 ℃, pressure 0.2MPa sterilization 30 minutes.
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| CN104274472A (en) * | 2014-09-12 | 2015-01-14 | 安徽天安动物药业有限公司 | Compound sulfamonomethoxine sodium injection and preparation method thereof |
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| 贺延，等.双氯芬酸加DMARDs治疗风湿病临床研究.《武警医学》.2000,第12卷(第12期),696. * |
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