CN104473864B - Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof - Google Patents
Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof Download PDFInfo
- Publication number
- CN104473864B CN104473864B CN201410688237.3A CN201410688237A CN104473864B CN 104473864 B CN104473864 B CN 104473864B CN 201410688237 A CN201410688237 A CN 201410688237A CN 104473864 B CN104473864 B CN 104473864B
- Authority
- CN
- China
- Prior art keywords
- sodium sulfonate
- carbazochrome sodium
- purity
- carbazochrome
- glycerine
- 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
- 229960004353 carbazochrome sodium sulfonate Drugs 0.000 title claims abstract description 157
- 238000002360 preparation method Methods 0.000 title claims abstract description 56
- HLFCZZKCHVSOAP-WXIWBVQFSA-M sodium;(5e)-5-(carbamoylhydrazinylidene)-1-methyl-6-oxo-2,3-dihydroindole-2-sulfonate Chemical compound [Na+].NC(=O)N\N=C/1C(=O)C=C2N(C)C(S([O-])(=O)=O)CC2=C\1 HLFCZZKCHVSOAP-WXIWBVQFSA-M 0.000 title abstract 11
- 239000011159 matrix material Substances 0.000 claims abstract description 31
- 239000000829 suppository Substances 0.000 claims abstract description 29
- 239000002674 ointment Substances 0.000 claims abstract description 27
- 239000000499 gel Substances 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000004480 active ingredient Substances 0.000 claims abstract 3
- HLFCZZKCHVSOAP-DAMYXMBDSA-M sodium;(5z)-5-(carbamoylhydrazinylidene)-1-methyl-6-oxo-2,3-dihydroindole-2-sulfonate Chemical compound [Na+].NC(=O)N/N=C/1C(=O)C=C2N(C)C(S([O-])(=O)=O)CC2=C\1 HLFCZZKCHVSOAP-DAMYXMBDSA-M 0.000 claims description 171
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 90
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 64
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 58
- 239000008213 purified water Substances 0.000 claims description 50
- 235000011187 glycerol Nutrition 0.000 claims description 45
- 238000003756 stirring Methods 0.000 claims description 39
- 239000000758 substrate Substances 0.000 claims description 37
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 29
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 29
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 239000007787 solid Substances 0.000 claims description 19
- 238000013329 compounding Methods 0.000 claims description 18
- 238000010992 reflux Methods 0.000 claims description 18
- 239000012043 crude product Substances 0.000 claims description 17
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 16
- 108010010803 Gelatin Proteins 0.000 claims description 16
- 239000008273 gelatin Substances 0.000 claims description 16
- 229920000159 gelatin Polymers 0.000 claims description 16
- 235000019322 gelatine Nutrition 0.000 claims description 16
- 235000011852 gelatine desserts Nutrition 0.000 claims description 16
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 229920002125 Sokalan® Polymers 0.000 claims description 14
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 14
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 14
- 229960001631 carbomer Drugs 0.000 claims description 14
- 239000004615 ingredient Substances 0.000 claims description 14
- 229940082500 cetostearyl alcohol Drugs 0.000 claims description 13
- 239000012467 final product Substances 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 13
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 13
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 claims description 13
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 claims description 12
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 12
- 239000002202 Polyethylene glycol Substances 0.000 claims description 11
- 239000012071 phase Substances 0.000 claims description 11
- 229920001223 polyethylene glycol Polymers 0.000 claims description 11
- 239000008346 aqueous phase Substances 0.000 claims description 10
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 9
- 239000000706 filtrate Substances 0.000 claims description 9
- 229940079827 sodium hydrogen sulfite Drugs 0.000 claims description 9
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 8
- 238000004945 emulsification Methods 0.000 claims description 7
- -1 albolene Chemical compound 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000003755 preservative agent Substances 0.000 claims description 6
- 230000002335 preservative effect Effects 0.000 claims description 6
- 239000004094 surface-active agent Substances 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 5
- 230000008961 swelling Effects 0.000 claims description 5
- 239000000314 lubricant Substances 0.000 claims description 4
- 235000009508 confectionery Nutrition 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 229960005150 glycerol Drugs 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 229960004418 trolamine Drugs 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims 2
- 239000013049 sediment Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 16
- 229940079593 drug Drugs 0.000 abstract description 14
- 239000000047 product Substances 0.000 abstract description 8
- 206010067484 Adverse reaction Diseases 0.000 abstract description 4
- 230000006838 adverse reaction Effects 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 2
- 239000006227 byproduct Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 19
- 230000000694 effects Effects 0.000 description 12
- 238000001514 detection method Methods 0.000 description 10
- 239000012535 impurity Substances 0.000 description 9
- BNOODXBBXFZASF-UHFFFAOYSA-N [Na].[S] Chemical compound [Na].[S] BNOODXBBXFZASF-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000007605 air drying Methods 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000004051 gastric juice Anatomy 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229940082484 carbomer-934 Drugs 0.000 description 2
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000003020 moisturizing effect Effects 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- CELKBRMLNUNCIP-HTFHIHPASA-M sodium;2-hydroxybenzoate;[(e)-(3-hydroxy-1-methyl-6-oxo-2,3-dihydroindol-5-ylidene)amino]urea Chemical class [Na+].OC1=CC=CC=C1C([O-])=O.NC(=O)N\N=C/1C(=O)C=C2N(C)CC(O)C2=C\1 CELKBRMLNUNCIP-HTFHIHPASA-M 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000003871 white petrolatum Substances 0.000 description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 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
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 206010071229 Procedural haemorrhage Diseases 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 206010051373 Wound haemorrhage Diseases 0.000 description 1
- DNOWPGDHLKQUPV-UHFFFAOYSA-N [NH4+].CC#N.OP(O)([O-])=O Chemical compound [NH4+].CC#N.OP(O)([O-])=O DNOWPGDHLKQUPV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229950006142 carbazochrome salicylate Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000000025 haemostatic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medicines and in particular relates to a carbazochrome sodium sulfonate semisolid preparation and a preparation method thereof. The preparation method comprises the following steps: with high-purity carbazochrome sodium sulfonate with the purity above 99.80 percent as an active ingredient, adding a medical matrix to prepare one of suppository, ointment and gel; wherein every10g of the suppository contains 20-80mg of carbazochrome sodium sulfonate; the ointment per 10g contains 40-80mg of the carbazochrome sodium sulfonate; every 5g of the gel contains 40-80mg of the carbazochrome sodium sulfonate. According to the carbazochrome sodium sulfonate semisolid preparation and the preparation method disclosed by the invention, the purity of the carbazochrome sodium sulfonate serving as the active ingredient is above 99.80 percent and by-products are controlled to be below 0.2 percent; when the carbazochrome sodium sulfonate semisolid preparation is used, the adverse reaction incidence in the medication process can be lowered and the medication safety can be improved; meanwhile, the prepared carbazochrome sodium sulfonate semisolid preparation can be delivered by virtue of body cavities so that the high-purity carbazochrome sodium sulfonate is capable of improving the medication safety while high bioavailability of a product is ensured.
Description
Technical field
The present invention relates to pharmaceutical technology field is and in particular to a kind of Carbazochrome Sodium Sulfonate semisolid preparation and preparation method thereof.
Background technology
Carbazochrome Sodium Sulfonate is ground by Tian Bian Mitsubishi medicine Co., Ltd. (MITSUBISHI TANABE company) is former, Japanese
Health and human services department records into Pharmacopeia of Japan the 12nd edition, and chemical name is：1- methyl -6- oxo -2,3,5,6- tetrahydro indole -5- contracts
Semicarbazide -2- sodium sulfonate.
Carbazochrome Sodium Sulfonate is hemostatic of new generation, is the derivative of Carbazochrome Salicylate (adrenobazonum), and it introduces on molecular structure
Sodium group, the solubility overcoming Carbazochrome Salicylate is little, this compound must be made to create by the shortcoming of salicylic acid hydrotropy
Significantly haemostatic effect.
Carbazochrome Sodium Sulfonate can reduce the permeability of capillary, promote the retraction effect of capillary fracture end, increase capillary
Blood vessel, to the resistance damaged, stablize the acid mucopolysaccharide of capillary and surrounding tissue, promotion clotting factor and fibrin ferment
Activity and the dissolving of fibrinogen, for urinary system, UGI, respiratory tract and obstetrical and gynecological disease bleeding.To uropoiesis
System bleeding is more notable, also can be used for wound and operative hemorrhage.
At present domestic approval listing Carbazochrome Sodium Sulfonate be all in the form of injection use, have injection Carbazochrome Sodium Sulfonate,
Carbazochrome sodium sulfonate for injection, carbazochrime sodium sulfonate injection, Carbazochrome Sodium Sulfonate piece, wherein especially list factory with injection related preparations
Family many, be widely used.But in Carbazochrome Sodium Sulfonate injection building-up process produce some accessory substances may result in patient occur nausea,
The bad reactions such as the red, pain of dizziness and injection site.
Meanwhile, also part oral tablet, after entering in stomach, the hydrochloric acid in gastric juice in gastric juice can react, and destroys
The using effect of Carbazochrome Sodium Sulfonate tablet.Application prospect in view of this Carbazochrome Sodium Sulfonate, it is desirable to provide one kind can effectively overcome existing
There are technical disadvantages, and provide a kind of brand-new Carbazochrome Sodium Sulfonate semisolid preparation imperative.In view of this, the special proposition present invention.
Content of the invention
The first object of the present invention is to provide a kind of Carbazochrome Sodium Sulfonate semisolid preparation, is administered using in body cavities,
While ensureing product bioavilability, high-purity Carbazochrome Sodium Sulfonate can improve the security of medication, so that Carbazochrome Sodium Sulfonate is obtained extensively
Application.
The second object of the present invention there are provided a kind of preparation method of high-purity Carbazochrome Sodium Sulfonate semisolid preparation.
In order to realize the above-mentioned purpose of the present invention, spy employs the following technical solutions：
A kind of high-purity Carbazochrome Sodium Sulfonate semisolid preparation, with high-purity Carbazochrome Sodium Sulfonate more than 99.80% for the purity for having
Effect composition, adds the suppository that medicinal substrate makes, ointment, one of gel；
Suppository 20～80mg containing Carbazochrome Sodium Sulfonate described in every 10g；40-80mg containing Carbazochrome Sodium Sulfonate in ointment described in every 10g；Often
40-80mg containing Carbazochrome Sodium Sulfonate in gel described in 5g.
The semisolid preparation containing high-purity Carbazochrome Sodium Sulfonate of present invention preparation, its active component Carbazochrome Sodium Sulfonate purity exists
More than 99.80%, accessory substance controls below 0.2%, can reduce use using the high-purity Carbazochrome Sodium Sulfonate preparation that the present invention provides
Adverse reaction rate during medicine, and drug safety can be improved.The Carbazochrome Sodium Sulfonate semisolid preparation being simultaneously manufactured, can
So that by being administered in body cavities, while ensureing product bioavilability, high-purity Carbazochrome Sodium Sulfonate can improve the peace of medication
Quan Xing.
On the basis of above technical scheme, the present invention can also do following improvement.
Further, described medicinal substrate is excipient, surfactant, absorbent, diluent, lubricant, preservative
One or more of combination.
Further, used in described suppository, medicinal substrate is：Gelatin, purified water, polyethylene glycol, glycerine, wherein, 1 part
The medicinal substrate Ingredient Amount of high-purity Carbazochrome Sodium Sulfonate compounding use is respectively：Gelatin 7.5-50 part, purified water 25-150 part, poly-
Ethylene glycol (400) 2.5-30 part, glycerine 50-200 part.Wherein, gelatin, purified water, polyethylene glycol, glycerine are the base of suppository
Matter, for carrying the material that may be formed into bolt of active component, can not only ensure the steady of suppository using above-mentioned matrix in suppository
Qualitative it is easy to preserve；And use when can in the presence of body temperature flash melt, improve medication efficiency.
Further, used in described ointment, medicinal substrate is：Glycerin monostearate, albolene, glycerine, 12
Sodium alkyl sulfate, ethyl hydroxy benzoate, benzalkonium bromide solution, dimethyl sulfoxide (DMSO), cetostearyl alcohol and purified water；Wherein, 1 part of high-purity
The medicinal substrate Ingredient Amount of Carbazochrome Sodium Sulfonate compounding use is respectively：Glycerin monostearate 6-50 part, albolene 6-50 part,
Glycerine 6-50 part, lauryl sodium sulfate 1-10 part, ethyl hydroxy benzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl
Sulfoxide 2.5-10 part, cetostearyl alcohol 6-50 part, purified water 25-150 part.Wherein, glycerin monostearate, dodecyl sulphate
Sodium, benzalkonium bromide solution are surfactant, play emulsification, albolene is lubricant and glycerine is diluent, oxybenzene
Ethyl ester is preservative, dimethyl sulfoxide (DMSO) is diluent, plays the effect of dissolved matrix, using above-mentioned matrix in ointment, not only
High-purity Carbazochrome Sodium Sulfonate ointment can be kept to be not easy in a long time oxidized, and be easy to absorb.
Further, used in described gel, medicinal substrate is：Viscosity be 934 Carbomer, triethanolamine, glycerine,
Ethyl hydroxy benzoate；Wherein, the medicinal substrate Ingredient Amount of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use is respectively：Carbomer 1-5 part,
Triethanolamine 0.1-2.5 part, glycerine 2.5-25 part, ethyl hydroxy benzoate 0.1-0.25 part.Wherein, viscosity is 934 Carbomer and sweet
Oil be matrix, triethanolamine be surfactant, play emulsification, the effect of moisturizing, ethyl hydroxy benzoate be preservative, using above-mentioned
Matrix as the matrix of gel, be not only difficult oxidized, be easy to preserve and use, and it is fast to be easy to infiltration rate.
Present invention also offers the method preparing a kind of aforesaid Carbazochrome Sodium Sulfonate semisolid preparation, by described high-purity card network
Sulphur sodium and described medicinal substrate are mixed and made into described Carbazochrome Sodium Sulfonate semisolid preparation.
Further, the method preparing described suppository includes：The medicinal substrate of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use becomes
Consumption is divided to be respectively：Gelatin 7.5-50 part, purified water 25-150 part, polyethylene glycol (400) 2.5-30 part, glycerine 50-200 part；
Suppository 20～80mg containing Carbazochrome Sodium Sulfonate described in every 10g；
According to described number, take gelatin, add purified water, placing 22-24 hour makes it fully soak, and adds proportional quantity
Glycerine and polyethylene glycol (400), heating for dissolving mixes as matrix；Add proportional quantity by measuring described medicinal substrate
After high-purity Carbazochrome Sodium Sulfonate mixes, after 70 DEG C of deaeration 2-3 hours, it is poured into cooled and solidified in mould and obtains final product.
Further, the method preparing described ointment includes：The medicinal substrate of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use
Ingredient Amount is respectively：Glycerin monostearate 6-50 part, albolene 6-50 part, glycerine 6-50 part, lauryl sodium sulfate
1-10 part, ethyl hydroxy benzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide (DMSO) 2.5-10 part, cetostearyl alcohol 6-
50 parts；Purified water 25-150 part；；40-80mg containing Carbazochrome Sodium Sulfonate in ointment described in every 10g；
According to described number, glycerine, lauryl sodium sulfate, ethyl hydroxy benzoate, dimethyl sulfoxide (DMSO), purified water, benzene are pricked bromine
Aqueous phase is mixed to obtain at ammonium salt solution and 100 DEG C of high-purity Carbazochrome Sodium Sulfonate；In proportion by cetostearyl alcohol, glycerin monostearate and white
Vaseline mixes to obtain oil phase at 90-95 DEG C；After aqueous phase and oil phase emulsification, homogeneous, cooling, embedding obtains final product.
Further, the method preparing described gel includes：The medicinal substrate of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use becomes
Consumption is divided to be respectively：Viscosity be 934 Carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerine 2.5-25 part, ethyl hydroxy benzoate
0.1-0.25 part, purified water 25-150 part；40-80mg containing Carbazochrome Sodium Sulfonate in gel described in every 5g；
According to described number, take the Carbomer that viscosity is 934 uniformly be spread on purifying water surface fully swelling, add three second
Hydramine stirs, and adjusting pH value is 5～6, obtains matrix；The high-purity Carbazochrome Sodium Sulfonate of proportional quantity, glycerine, ethyl hydroxy benzoate is taken to mix
Even, it is gradually added in the matrix under stirring, after adding purified water mixing, embedding obtains final product.
Further, high-purity Carbazochrome Sodium Sulfonate more than 99.80% for the purity, its preparation method comprises the following steps：
Step 1, add in the reaction vessel equipped with mechanical agitator sodium hydrogensulfite and deionized water with 70.0～
The speed stirring and dissolving of 80.0r/min, adds recipe quantity Adenaron, control reactant liquor at 15.0～25.0 DEG C with
The speed stirring reaction of 50.0～60.0r/min, after having orange/yellow solid to separate out, continues stirring 3～5 hours, filters, precipitate
Carbazochrome Sodium Sulfonate crude product；
Step 2, add gained Carbazochrome Sodium Sulfonate crude product and 10.0～15.0 times of quality in equipped with churned mechanically reaction bulb
Deionized water, solvent refluxing is stirred and heated to the speed of 50.0～60.0r/min, after solid dissolving, add prescription
Carbon content active, continues to be stirred at reflux 30～60 minutes, filters while hot, and filtrate is slowly lowered to room temperature crystallization 30-35 minute, mistake
Filter, is deposited in drying under reduced pressure 4-6 hour at 60.0 DEG C, obtains high-purity Carbazochrome Sodium Sulfonate.
Compared with prior art, beneficial effects of the present invention are：
1. the semisolid preparation containing high-purity Carbazochrome Sodium Sulfonate of present invention preparation, its active component Carbazochrome Sodium Sulfonate purity exists
More than 99.80%, accessory substance controls below 0.2%, can reduce adverse reaction rate using high-purity Carbazochrome Sodium Sulfonate preparation,
Improve drug safety.
2. the semisolid preparation containing high-purity Carbazochrome Sodium Sulfonate of present invention preparation is cavity/canal drug administration, with other oral administration solids
Preparation is compared, it is to avoid Carbazochrome Sodium Sulfonate is destroyed by hydrochloric acid in gastric juice, absorbs rapidly after entering body cavities, play local action it is ensured that
Product curative effect.
3. medication is convenient, patient can voluntarily medication, without relying on medical personnel.
Specific embodiment
Below in conjunction with embodiment, embodiment of the present invention is described in detail, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and be not construed as limiting the scope of the present invention.Unreceipted concrete in embodiment
Condition person, the condition according to normal condition or manufacturer's suggestion is carried out.Agents useful for same or the unreceipted production firm person of instrument, are
Can be by the commercially available conventional products bought and obtain.
A kind of high-purity Carbazochrome Sodium Sulfonate semisolid preparation, with high-purity Carbazochrome Sodium Sulfonate more than 99.80% for the purity for having
Effect composition, adds the suppository that medicinal substrate makes, ointment, one of gel；
Suppository 20～80mg containing Carbazochrome Sodium Sulfonate described in every 10g；40-80mg containing Carbazochrome Sodium Sulfonate in ointment described in every 10g；Often
40-80mg containing Carbazochrome Sodium Sulfonate in gel described in 5g.
The semisolid preparation containing high-purity Carbazochrome Sodium Sulfonate of present invention preparation, its active component Carbazochrome Sodium Sulfonate purity exists
More than 99.80%, accessory substance controls below 0.2%, can reduce use using the high-purity Carbazochrome Sodium Sulfonate preparation that the present invention provides
Adverse reaction rate during medicine, and drug safety can be improved.The Carbazochrome Sodium Sulfonate semisolid preparation being simultaneously manufactured, can
So that by being administered in body cavities, while ensureing product bioavilability, high-purity Carbazochrome Sodium Sulfonate can improve the peace of medication
Quan Xing.
On the basis of above technical scheme, the present invention can also do following improvement.
Further, described medicinal substrate is excipient, surfactant, absorbent, diluent, lubricant, preservative
One or more of combination.
Further, used in described suppository, medicinal substrate is：Gelatin, purified water, polyethylene glycol, glycerine, wherein, 1 part
The medicinal substrate Ingredient Amount of high-purity Carbazochrome Sodium Sulfonate compounding use is respectively：Gelatin 7.5-50 part, purified water 25-150 part, poly-
Ethylene glycol (400) 2.5-30 part, glycerine 50-200 part.Wherein, gelatin, purified water, polyethylene glycol, glycerine are the base of suppository
Matter, for carrying the material that may be formed into bolt of active component, can not only ensure the steady of suppository using above-mentioned matrix in suppository
Qualitative it is easy to preserve；And use when can in the presence of body temperature flash melt, improve medication efficiency.
Further, used in described ointment, medicinal substrate is：Glycerin monostearate, albolene, glycerine, 12
Sodium alkyl sulfate, ethyl hydroxy benzoate, benzalkonium bromide solution, dimethyl sulfoxide (DMSO), cetostearyl alcohol and purified water；Wherein, 1 part of high-purity
The medicinal substrate Ingredient Amount of Carbazochrome Sodium Sulfonate compounding use is respectively：Glycerin monostearate 6-50 part, albolene 6-50 part,
Glycerine 6-50 part, lauryl sodium sulfate 1-10 part, ethyl hydroxy benzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl
Sulfoxide 2.5-10 part, cetostearyl alcohol 6-50 part, purified water 25-150 part.Wherein, glycerin monostearate, dodecyl sulphate
Sodium, benzalkonium bromide solution are surfactant, play emulsification, albolene and glycerine are matrix), ethyl hydroxy benzoate be anti-
Rotten agent, dimethyl sulfoxide (DMSO) are diluent, play the effect of dissolved matrix, using above-mentioned matrix in ointment, can not only keep
High-purity Carbazochrome Sodium Sulfonate ointment be not easy in a long time oxidized, and be easy to absorb.
Further, used in described gel, medicinal substrate is：Viscosity be 934 Carbomer, triethanolamine, glycerine,
Ethyl hydroxy benzoate；Wherein, the medicinal substrate Ingredient Amount of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use is respectively：Carbomer 1-5 part,
Triethanolamine 0.1-2.5 part, glycerine 2.5-25 part, ethyl hydroxy benzoate 0.1-0.25 part.Wherein, viscosity is 934 Carbomer and sweet
Oil be matrix, triethanolamine be emulsifying agent, play emulsification, the effect of moisturizing, ethyl hydroxy benzoate be preservative, using above-mentioned matrix
As the matrix of gel, be not only difficult oxidized, be easy to preserve and use, and it is fast to be easy to infiltration rate.
Present invention also offers the method preparing a kind of aforesaid Carbazochrome Sodium Sulfonate semisolid preparation, by described high-purity card network
Sulphur sodium and described medicinal substrate are mixed and made into described Carbazochrome Sodium Sulfonate semisolid preparation.
Further, the method preparing described suppository includes：The medicinal substrate of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use becomes
Consumption is divided to be respectively：Gelatin 7.5-50 part, purified water 25-150 part, polyethylene glycol (400) 2.5-30 part, glycerine 50-200 part；
Suppository 20～80mg containing Carbazochrome Sodium Sulfonate described in every 10g；
According to described number, take gelatin, add purified water, placing 22-24 hour makes it fully soak, and adds proportional quantity
Glycerine and polyethylene glycol (400), heating for dissolving mixes as matrix；Add proportional quantity by measuring described medicinal substrate
After high-purity Carbazochrome Sodium Sulfonate mixes, after 70 DEG C of deaeration 2-3 hours, it is poured into cooled and solidified in mould and obtains final product.
Further, the method preparing described ointment includes：The medicinal substrate of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use
Ingredient Amount is respectively：Glycerin monostearate 6-50 part, albolene 6-50 part, glycerine 6-50 part, lauryl sodium sulfate
1-10 part, ethyl hydroxy benzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide (DMSO) 2.5-10 part；Cetostearyl alcohol 6-
50 parts；Purified water 25-150 part；40-80mg containing Carbazochrome Sodium Sulfonate in ointment described in every 10g；
According to described number, glycerine, lauryl sodium sulfate, ethyl hydroxy benzoate, dimethyl sulfoxide (DMSO), purified water, benzene are pricked bromine
Aqueous phase is mixed to obtain at ammonium salt solution and 100 DEG C of high-purity Carbazochrome Sodium Sulfonate；In proportion by cetostearyl alcohol, glycerin monostearate and white
Vaseline mixes to obtain oil phase at 90-95 DEG C；After aqueous phase and oil phase emulsification, homogeneous, cooling, embedding obtains final product.
Further, the method preparing described gel includes：The medicinal substrate of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use becomes
Consumption is divided to be respectively：Viscosity be 934 Carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerine 2.5-25 part, ethyl hydroxy benzoate
0.1-0.25 part, Purified Water q. s 25-150 part；40-80mg containing Carbazochrome Sodium Sulfonate in gel described in every 5g；
According to described number, take the Carbomer that viscosity is 934 uniformly be spread on purifying water surface fully swelling, add three second
Hydramine stirs, and adjusting pH value is 5～6, obtains matrix；The high-purity Carbazochrome Sodium Sulfonate of proportional quantity, glycerine, ethyl hydroxy benzoate is taken to mix
Even, it is gradually added in the matrix under stirring, after adding purified water mixing, embedding obtains final product.
Further, high-purity Carbazochrome Sodium Sulfonate more than 99.80% for the purity, its preparation method comprises the following steps：
Step 1, add 20.8 parts of sodium hydrogensulfite and deionized water in the reaction vessel equipped with mechanical agitator
100ml, with the speed stirring and dissolving of 70.0～80.0r/min, adds 23.6 parts of Adenaron, controls reactant liquor 15.0
With the speed stirring reaction of 50.0～60.0r/min at～25.0 DEG C, after having orange/yellow solid to separate out, continue stirring 3～5 little
When, filter, precipitate to obtain Carbazochrome Sodium Sulfonate crude product；
Step 2, add gained Carbazochrome Sodium Sulfonate crude product and 10.0～15.0 times of quality in equipped with churned mechanically reaction bulb
Deionized water, solvent refluxing is stirred and heated to the speed of 50.0～60.0r/min, after solid dissolving, add activity
1.0 parts of charcoal, continues to be stirred at reflux 30～60 minutes, filters while hot, and filtrate is slowly lowered to room temperature crystallization 30-35 minute, filters,
It is deposited in drying under reduced pressure 4-6 hour at 60.0 DEG C, obtain high-purity Carbazochrome Sodium Sulfonate.
Embodiment 1：Prepare Carbazochrome Sodium Sulfonate suppository 1
Sodium hydrogensulfite 20.8g, purified water 100mL, stirring is added in equipped with churned mechanically 250mL reaction bulb
(75r/min) to dissolving, mixing speed is down to 55.0r/min, plus cold bath temperature control makes reacting liquid temperature 18.0 DEG C～19.0
DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 3 hours, filter, obtain orange-yellow Carbazochrome Sodium Sulfonate thick
Product 41.6g.
41.6g crude product and 416g purified water, stirring is added in reactor in equipped with churned mechanically 500mL reaction bulb
(53.r/min) and be heated to solvent refluxing, after solid dissolving, add 1.0g activated carbon, continue to be stirred at reflux 30 minutes, take advantage of
Heat filtering, filtrate is slowly lowered to 14 DEG C, crystallization 30 minutes, filters, is deposited in 60 DEG C of forced air dryings 6 hours, obtains Carbazochrome Sodium Sulfonate
Fine work 32.1g.
Through HPLC detection, Adenaron is 0.05%, and in addition to Adenaron, each impurity is 0.08%, and Carbazochrome Sodium Sulfonate has
Closing material is 0.13%.
Prepared by suppository：Take gelatin 40g, add purified water 120g, placing makes it fully soak in 24 hours, add glycerine 100g
With PEG400 20g, heating for dissolving mixes as matrix, takes 175g matrix to add high-purity Carbazochrome Sodium Sulfonate 1g mixing
After uniformly, in 70 DEG C of deaerations 2 hours, it is poured in vaginal plug mould, cooling, solidification, obtain final product 50 pieces of Carbazochrome Sodium Sulfonate bolt.
Embodiment 2 prepares Carbazochrome Sodium Sulfonate suppository 2
Sodium hydrogensulfite 20.8g, purified water 100mL, stirring is added in equipped with churned mechanically 250mL reaction bulb
(70r/min) to dissolving, mixing speed is down to 55.6r/min, plus cold bath temperature control makes reacting liquid temperature 18.5 DEG C～19.5
DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 3.5 hours, filter, obtain orange-yellow Carbazochrome Sodium Sulfonate
Crude product 41.8g.
41.8g crude product and 418g purified water, stirring is added in reactor in equipped with churned mechanically 500mL reaction bulb
(55.5r/min) and be heated to solvent refluxing, after solid dissolving, add 1.0g activated carbon, continue to be stirred at reflux 30 minutes, take advantage of
Heat filtering, filtrate is slowly lowered to 14.5 DEG C, crystallization 30 minutes, filters, is deposited in 60 DEG C of forced air dryings 5.5 hours, obtains card network
Sulphur sodium fine work 32.4g.
Through HPLC detection, Adenaron is 0.04%, and in addition to Adenaron, each impurity is 0.08%, and Carbazochrome Sodium Sulfonate has
Closing material is 0.14%.
Prepared by suppository：Take gelatin 40g, add purified water 120g, placing makes it fully soak in 24 hours, add glycerine 100g
With PEG400 20g, heating for dissolving mixes as matrix, takes 175g matrix to add high-purity Carbazochrome Sodium Sulfonate 2g mixing
After uniformly, in 70 DEG C of deaerations 2 hours, it is poured in vaginal plug mould, cooling, solidification, obtain final product 50 pieces of Carbazochrome Sodium Sulfonate bolt.
Embodiment 3：Prepare Carbazochrome Sodium Sulfonate ointment 1
Sodium hydrogensulfite 20.8g, purified water 100mL, stirring is added in equipped with churned mechanically 250mL reaction bulb
(73r/min) to dissolving, mixing speed is down to 56.1r/min, plus cold bath temperature control makes reacting liquid temperature 19.0 DEG C～20.0
DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 4.0 hours, filter, obtain orange-yellow Carbazochrome Sodium Sulfonate
Crude product 41.2g.
41.2g crude product and 412g purified water, stirring is added in reactor in equipped with churned mechanically 500mL reaction bulb
(56.1r/min) and be heated to solvent refluxing, after solid dissolving, add 1.0g activated carbon, continue to be stirred at reflux 30 minutes, take advantage of
Heat filtering, filtrate is slowly lowered to 15.2 DEG C, crystallization 30 minutes, filters, is deposited in 60 DEG C of forced air dryings 5 hours, obtains card network sulphur
Sodium fine work 32.5g.
Through HPLC detection, Adenaron is 0.04%, and in addition to Adenaron, each impurity is 0.07%, and Carbazochrome Sodium Sulfonate has
Closing material is 0.11%.
Prepared by ointment：By glycerine 100.0g, lauryl sodium sulfate 20.0g, ethyl hydroxy benzoate 5.0g, dimethyl sulfoxide (DMSO)
20.0g, benzalkonium bromide solution 10.0g purified water 550.0g and high-purity Carbazochrome Sodium Sulfonate 8g mix to obtain aqueous phase at 100 DEG C；By ten
Six octadecyl alcolol 100.0g, glycerin monostearate 100.0g and albolene 100.0g mix 30 minutes to obtain oil phase at 95 DEG C；
By aqueous phase, vacuum in emulsion tank is to stir 30 minutes under 0.05MPa with oil phase, then homogeneous (3000r/min) 35 minutes,
It is cooled to 50 DEG C, embedding obtains final product Carbazochrome Sodium Sulfonate ointment 200.
Embodiment 4：Prepare Carbazochrome Sodium Sulfonate ointment 2
Sodium hydrogensulfite 20.8g, purified water 100mL, stirring is added in equipped with churned mechanically 250mL reaction bulb
(77r/min) to dissolving, mixing speed is down to 56.5r/min, plus cold bath temperature control makes reacting liquid temperature 18.3 DEG C～19.5
DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 4.5 hours, filter, obtain orange-yellow Carbazochrome Sodium Sulfonate
Crude product 41.4g.
41.4g crude product and 414g purified water, stirring is added in reactor in equipped with churned mechanically 500mL reaction bulb
(56.5r/min) and be heated to solvent refluxing, after solid dissolving, add 1.0g activated carbon, continue to be stirred at reflux 30 minutes, take advantage of
Heat filtering, filtrate is slowly lowered to 15.5 DEG C, crystallization 30 minutes, filters, is deposited in 60 DEG C of forced air dryings 5.5 hours, obtains card network
Sulphur sodium fine work 32.1g.
Through HPLC detection, Adenaron is 0.04%, and in addition to Adenaron, each impurity is 0.08%, and Carbazochrome Sodium Sulfonate has
Closing material is 0.12%.
Prepared by ointment：By glycerine 100.0g, lauryl sodium sulfate 20.0g, ethyl hydroxy benzoate 5.0g, dimethyl sulfoxide (DMSO)
20.0g, benzalkonium bromide solution 10.0g purified water 550.0g and high-purity Carbazochrome Sodium Sulfonate 16g mix to obtain aqueous phase at 100 DEG C；Will
Cetostearyl alcohol 100.0g, glycerin monostearate 100.0g and albolene 100.0g mix 30 minutes oily at 95 DEG C
Phase；By aqueous phase, vacuum in emulsion tank is to stir 30 minutes under 0.05MPa with oil phase, then 35 points of homogeneous (3000r/min)
Clock, is cooled to 50 DEG C, and embedding obtains final product Carbazochrome Sodium Sulfonate ointment 200.
Embodiment 5：Prepare Carbazochrome Sodium Sulfonate gel 1
Sodium hydrogensulfite 20.8g, purified water 100mL, stirring is added in equipped with churned mechanically 250mL reaction bulb
(78r/min) to dissolving, mixing speed is down to 56.5r/min, plus cold bath temperature control makes reacting liquid temperature 18.5 DEG C～19.5
DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 4.5 hours, filter, obtain orange-yellow Carbazochrome Sodium Sulfonate
Crude product 41.3g.
41.3g crude product and 413g purified water, stirring is added in reactor in equipped with churned mechanically 500mL reaction bulb
(56.5r/min) and be heated to solvent refluxing, after solid dissolving, add 1.0g activated carbon, continue to be stirred at reflux 30 minutes, take advantage of
Heat filtering, filtrate is slowly lowered to 16.0 DEG C, crystallization 30 minutes, filters, is deposited in 60 DEG C of forced air dryings 5.0 hours, obtains card network
Sulphur sodium fine work 32.2g.
Through HPLC detection, Adenaron is 0.04%, and in addition to Adenaron, each impurity is 0.08%, and Carbazochrome Sodium Sulfonate has
Closing material is 0.12%.
Prepare gel：Take 10.0g carbomer 934 to be uniformly spread on 600.0g and purify water surface, place 40～45 hours fully
Swelling 4.0g tri- ethanol that adds stirs, and adjusts pH5～6, obtains matrix；Take high-purity Carbazochrome Sodium Sulfonate 8.0g, glycerine 120.0g,
Ethyl hydroxy benzoate 1.0g mixes, and is gradually added in the matrix under stirring, and after adding the mixing of 250.0g purified water, embedding must block
Network sulphur sodium gel 200.
Embodiment 6：Prepare Carbazochrome Sodium Sulfonate gel 2
Sodium hydrogensulfite 20.8g, purified water 100mL, stirring is added in equipped with churned mechanically 250mL reaction bulb
(80r/min) to dissolving, mixing speed is down to 56.8r/min, plus cold bath temperature control makes reacting liquid temperature 18.5 DEG C～20.0
DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 5.0 hours, filter, obtain orange-yellow Carbazochrome Sodium Sulfonate
Crude product 41.5g.
41.5g crude product and 415g purified water, stirring is added in reactor in equipped with churned mechanically 500mL reaction bulb
(56.8r/min) and be heated to solvent refluxing, after solid dissolving, add 1.0g activated carbon, continue to be stirred at reflux 30 minutes, take advantage of
Heat filtering, filtrate is slowly lowered to 16.0 DEG C, crystallization 30 minutes, filters, is deposited in 60 DEG C of forced air dryings 5.5 hours, obtains card network
Sulphur sodium fine work 32.3g.
Through HPLC detection, Adenaron is 0.03%, and in addition to Adenaron, each impurity is 0.08%, and Carbazochrome Sodium Sulfonate has
Closing material is 0.11%.
Prepare gel：Take 10.0g carbomer 934 to be uniformly spread on 600.0g and purify water surface, place 40～45 hours fully
Swelling 4.0g tri- ethanol that adds stirs, and adjusts pH5～6, obtains matrix；Take high-purity Carbazochrome Sodium Sulfonate 16.0g, glycerine
120.0g, ethyl hydroxy benzoate 1.0g mix, and are gradually added in the matrix under stirring, after adding the mixing of 250.0g purified water,
Embedding obtains Carbazochrome Sodium Sulfonate gel 200.
Experimental example 1
The HPLC detection being related in the embodiment of the present invention adopts following detection method：
Chromatographic condition：
Chromatographic column：C18((250mm × 4.6mm, 5 μm)
Mobile phase：0.12% ammonium dihydrogen phosphate-acetonitrile (91：9, pH=3.0)
Flow velocity：1.0mL/min
Column temperature：30.0℃
Detection wavelength：363nm
Theoretical cam curve is no less than 3000
Determination method：Take this product 25-150 part, accurately weighed, plus flowing phased soln quantitative dilution make every 1mL containing about
The solution of 0.5mg, as need testing solution, precision measures 0.1mL, puts in 100mL measuring bottle, is diluted with water to scale, shakes up, and makees
For contrast solution；Separately take Adenaron reference substance about 25mg, accurately weighed, put in 50mL measuring bottle, dissolved with methyl alcohol and dilute
To scale, shake up, precision measures 0.1mL, put in 100mL measuring bottle, be diluted with water to scale, spectrometer, adjust detection sensitivity, make
The peak height of principal component chromatographic peak is the 25% of full scale, then precision to measure need testing solution each with Adenaron reference substance solution
20 μ l, are injected separately into liquid chromatograph, 2 times of record chromatogram to principal component peak retention time, the chromatogram of need testing solution
In as aobvious impurity peaks, Adenaron must not calculate 0.1% with peak area by external standard method, and the peak area of other single impurity is not
Must be more than contrast solution main peak area 1/2 (0.05%), except Adenaron in addition to the peak area of each impurity with cannot be greater than
Contrast solution main peak area (0.1%).
Experimental example 2：High-purity Carbazochrome Sodium Sulfonate semisolid preparation clinical observation
Method：The patient of 81 clinical definite hemorrhages of digestive tract is randomly divided into treatment group 41, control group 40, respectively
High-purity Carbazochrome Sodium Sulfonate bolt and commercially available Carbazochrome Sodium Sulfonate piece, continuously use 15 days, and period stops other treatment.
(1) criterion of therapeutical effect：
Cure：Symptom sign disappears, and laboratory examination is normal；
Effectively：Symptom sign is not wholly absent, and laboratory examination has improvement；
Invalid：Unchanged before and after symptom, sign and laboratory examination treatment.
(2) safety standard：
Safety：Have no bad reaction symptom
Typically：Slight nausea, vertigo symptoms, has no that other are abnormal
Dangerous：More serious bad reaction symptom and other abnormal responses occur
(3) observe result：Two groups of clinical efficacies are shown in Table 1, and two groups of clinical applications are shown in Table safely 2.
Table 1 high-purity Carbazochrome Sodium Sulfonate suppository clinical observation on the therapeutic effect
Table 2 high-purity Carbazochrome Sodium Sulfonate suppository clinical safety is observed
As can be seen from the above table, preparation of the present invention clinically, obtains preferable curative effect, and 41 patients take this
Bright described preparation has no bad reaction after 15 days, obtain the therapeutic effect better than tablet, and described preparation has no bad reaction, piece
Agent produces 5% general bad reaction.
Although illustrate and describing the present invention with specific embodiment, but it will be appreciated that without departing substantially from the present invention's
Many other changes can be made in the case of spirit and scope and change.It is, therefore, intended that in the following claims
Including all such changes and modifications belonging in the scope of the invention.
Claims (9)
1. a kind of Carbazochrome Sodium Sulfonate semisolid preparation is it is characterised in that the high-purity Carbazochrome Sodium Sulfonate more than 99.80% is with purity
Active ingredient, adds the suppository that medicinal substrate makes, ointment, one of gel；
Suppository 20～80mg containing Carbazochrome Sodium Sulfonate described in every 10g；40-80mg containing Carbazochrome Sodium Sulfonate in ointment described in every 10g；Every 5g institute
State 40-80mg containing Carbazochrome Sodium Sulfonate in gel；
High-purity Carbazochrome Sodium Sulfonate more than 99.80% for the described purity, its preparation method comprises the following steps：
Step 1, add sodium hydrogensulfite 20.8g and deionized water 100mL in the reaction vessel equipped with mechanical agitator, with
The speed stirring and dissolving of 70.0～80.0r/min, adds 23.6 parts of Adenaron, controls reactant liquor at 15.0～25.0 DEG C
Under with the speed stirring reaction of 50.0～60.0r/min, after having orange/yellow solid to separate out, continue stirring 3～5 hours, filter, sink
Form sediment to obtain Carbazochrome Sodium Sulfonate crude product；
Step 2, add going of gained Carbazochrome Sodium Sulfonate crude product and 10.0～15.0 times of quality in equipped with churned mechanically reaction bulb
Ionized water, is stirred and heated to solvent refluxing with the speed of 50.0～60.0r/min, after solid dissolving, adds carbon content active
1.0 parts, continue to be stirred at reflux 30～60 minutes, filter while hot, filtrate is slowly lowered to room temperature crystallization 30-35 minute, filter, sink
Shallow lake drying under reduced pressure 4-6 hour at 60.0 DEG C, obtains high-purity Carbazochrome Sodium Sulfonate.
2. according to claim 1 Carbazochrome Sodium Sulfonate semisolid preparation it is characterised in that described medicinal substrate be surface-active
Agent, diluent, lubricant, one or more of preservative of combination.
3. according to claim 2 Carbazochrome Sodium Sulfonate semisolid preparation it is characterised in that medicinal substrate used in described suppository
For：Gelatin, purified water, polyethylene glycol, glycerine, wherein, the medicinal substrate Ingredient Amount of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use
It is respectively：Gelatin 7.5-50 part, purified water 25-150 part, PEG400 2.5-30 part, glycerine 50-200 part.
4. according to claim 2 Carbazochrome Sodium Sulfonate semisolid preparation it is characterised in that medicinal base used in described ointment
Matter is：Glycerin monostearate, albolene, glycerine, lauryl sodium sulfate, ethyl hydroxy benzoate, benzalkonium bromide solution, dimethyl
Sulfoxide, cetostearyl alcohol and purified water；Wherein, the medicinal substrate Ingredient Amount difference of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use
For：Glycerin monostearate 6-50 part, albolene 6-50 part, glycerine 6-50 part, lauryl sodium sulfate 1-10 part, oxybenzene second
Ester 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide (DMSO) 2.5-10 part, cetostearyl alcohol 6-50 part, purified water 25-
150 parts.
5. according to claim 2 Carbazochrome Sodium Sulfonate semisolid preparation it is characterised in that medicinal base used in described gel
Matter is：Viscosity be 934 Carbomer, triethanolamine, glycerine, ethyl hydroxy benzoate；Wherein, 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use
Medicinal substrate Ingredient Amount be respectively：Carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerine 2.5-25 part, ethyl hydroxy benzoate
0.1-0.25 part, purified water 25-150 part.
6. a kind of method of the Carbazochrome Sodium Sulfonate semisolid preparation described in preparation any one of claim 1-5 is it is characterised in that by institute
State high-purity Carbazochrome Sodium Sulfonate and be mixed and made into described Carbazochrome Sodium Sulfonate semisolid preparation with described medicinal substrate.
7. according to claim 6 prepare a kind of method of Carbazochrome Sodium Sulfonate semisolid preparation it is characterised in that
The method preparing described suppository includes：The medicinal substrate Ingredient Amount of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use is respectively：
Gelatin 7.5-50 part, purified water 25-150 part, PEG400 2.5-30 part, glycerine 50-200 part；Suppository described in every 10g contains
Carbazochrome Sodium Sulfonate 20～80mg；
According to described number, take gelatin, add purified water, placing 22-24 hour makes it fully soak, and adds the sweet of proportional quantity
Oil and PEG400, heating for dissolving mixes as matrix；By the high-purity measuring described medicinal substrate addition proportional quantity
After Carbazochrome Sodium Sulfonate mixes, after 70 DEG C of deaeration 2-3 hours, it is poured into cooled and solidified in mould and obtains final product.
8. according to claim 6 prepare a kind of method of Carbazochrome Sodium Sulfonate semisolid preparation it is characterised in that
The method preparing described ointment includes：The medicinal substrate Ingredient Amount of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use is respectively
For：Glycerin monostearate 6-50 part, albolene 6-50 part, glycerine 6-50 part, lauryl sodium sulfate 1-10 part, oxybenzene second
Ester 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide (DMSO) 2.5-10 part, cetostearyl alcohol 6-50 part；Purified water 25-
150 parts；40-80mg containing Carbazochrome Sodium Sulfonate in ointment described in every 10g；
According to described number, will be molten to glycerine, lauryl sodium sulfate, ethyl hydroxy benzoate, dimethyl sulfoxide (DMSO), purified water, benzalkonium bromide
Aqueous phase is mixed to obtain at liquid and 100 DEG C of high-purity Carbazochrome Sodium Sulfonate；In proportion by cetostearyl alcohol, glycerin monostearate and Bai Fanshi
Woods mixes to obtain oil phase at 90-95 DEG C；After aqueous phase and oil phase emulsification, homogeneous, cooling, embedding obtains final product.
9. according to claim 6 prepare a kind of method of Carbazochrome Sodium Sulfonate semisolid preparation it is characterised in that
The method preparing described gel includes：The medicinal substrate Ingredient Amount of 1 part of high-purity Carbazochrome Sodium Sulfonate compounding use is respectively：
Viscosity be 934 Carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerine 2.5-25 part, ethyl hydroxy benzoate 0.1-0.25 part, purify
Water 25-150 part；40-80mg containing Carbazochrome Sodium Sulfonate in gel described in every 5g；
According to described number, take the Carbomer that viscosity is 934 uniformly be spread on purifying water surface fully swelling, add triethanolamine
Stir, adjusting pH value is 5～6, obtains matrix；The high-purity Carbazochrome Sodium Sulfonate of proportional quantity, glycerine, ethyl hydroxy benzoate is taken to mix, by
Gradually add in the matrix under stirring, after adding purified water mixing, embedding obtains final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410688237.3A CN104473864B (en) | 2014-11-25 | 2014-11-25 | Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410688237.3A CN104473864B (en) | 2014-11-25 | 2014-11-25 | Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104473864A CN104473864A (en) | 2015-04-01 |
| CN104473864B true CN104473864B (en) | 2017-02-22 |
Family
ID=52748570
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410688237.3A Active CN104473864B (en) | 2014-11-25 | 2014-11-25 | Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104473864B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382818A (en) * | 2017-08-03 | 2017-11-24 | 江苏汉斯通药业有限公司 | A kind of synthetic method of high cleanliness Carbazochrome Sodium Sulfonate |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA002967B1 (en) * | 1998-04-21 | 2002-12-26 | Тейдзин Лимитед | Medical compositions for application to mucosa |
| CN1562001A (en) * | 2004-03-29 | 2005-01-12 | 南昌弘益科技有限公司 | Carbazochrome sodium sulfoate dripping pill and its preparing method |
| CN101554377A (en) * | 2008-04-09 | 2009-10-14 | 鲁南制药集团股份有限公司 | Pharmaceutical composition containing prasugrel and carbazochrome sodium sulfonate |
| CN102018675A (en) * | 2009-11-11 | 2011-04-20 | 海南利能康泰制药有限公司 | Carbazochrome sodium sulfonate freeze-dried powder injection and preparation method thereof |
| CN102125559A (en) * | 2010-01-17 | 2011-07-20 | 鲁南制药集团股份有限公司 | Pharmaceutical composition containing pentoxifylline and carbazochrome sodium sulfonate and application thereof |
| CN102757378A (en) * | 2012-07-06 | 2012-10-31 | 江苏汉斯通药业有限公司 | Preparation method of carbazochrome sodium sulfonate |
-
2014
- 2014-11-25 CN CN201410688237.3A patent/CN104473864B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA002967B1 (en) * | 1998-04-21 | 2002-12-26 | Тейдзин Лимитед | Medical compositions for application to mucosa |
| CN1562001A (en) * | 2004-03-29 | 2005-01-12 | 南昌弘益科技有限公司 | Carbazochrome sodium sulfoate dripping pill and its preparing method |
| CN101554377A (en) * | 2008-04-09 | 2009-10-14 | 鲁南制药集团股份有限公司 | Pharmaceutical composition containing prasugrel and carbazochrome sodium sulfonate |
| CN102018675A (en) * | 2009-11-11 | 2011-04-20 | 海南利能康泰制药有限公司 | Carbazochrome sodium sulfonate freeze-dried powder injection and preparation method thereof |
| CN102125559A (en) * | 2010-01-17 | 2011-07-20 | 鲁南制药集团股份有限公司 | Pharmaceutical composition containing pentoxifylline and carbazochrome sodium sulfonate and application thereof |
| CN102757378A (en) * | 2012-07-06 | 2012-10-31 | 江苏汉斯通药业有限公司 | Preparation method of carbazochrome sodium sulfonate |
Non-Patent Citations (1)
| Title |
|---|
| "卡络磺钠片的处方工艺研究";聂延君等;《中国药业》;20111120;第20卷(第24期);第54-55页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104473864A (en) | 2015-04-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MXPA05002549A (en) | Crystal for oral solid drug and oral solid drug for dysuria treatment containing the same. | |
| CN105418601A (en) | Tetrahydrocoptisine derivative and applications thereof | |
| CN101987094B (en) | Ornithine aspartate injection and preparation method thereof | |
| CN105531259A (en) | Pyrrolidine derivatives as oxytocin / vasopressin v1a receptors antagonists | |
| CN103429239A (en) | Methods for increasing reticulocyte hemoglobin content | |
| CN110078780B (en) | Preparation method and application of progesterone eutectic | |
| CN101434635B (en) | Water-soluble phenolic triterpenoid with anti-tumor activity and preparation method thereof | |
| WO2004111027A1 (en) | The isoflavone derivatives of tectoridin, the preparation thereof and the anti-virus medicines containing the same as the effective constituents | |
| CN107714642A (en) | A kind of oral solution of EV71 viruses and CVA16 viral inhibitors and preparation method thereof | |
| Li et al. | Improving anti-tumor outcomes for colorectal cancer therapy through in situ thermosensitive gel loading harmine | |
| CN101935334A (en) | Berberine glycyrrhetinic acid enantiomeric salts and preparation method and application thereof | |
| CN104473864B (en) | Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof | |
| CN103159664B (en) | A kind of Silodosin bulk drug and preparation method thereof, pharmaceutical composition | |
| CN103298786A (en) | Salts of arylsulfonamide ccr3 antagonists | |
| JP2005082512A (en) | Preparation for external use improved in percutaneous absorbability of ionic medicament | |
| KR20190010578A (en) | New Dapagliflozoline Crystal Forms and Methods of Making and Uses Thereof | |
| CN104490762B (en) | A kind of tranexamic acid external use semi-solid preparation and preparation method | |
| CN104334530A (en) | Solid state forms of n-((s)-2,3-dihydroxy-propyl)-3-(2-fluoro-4-iodo-phenylamino)-isonicotinamide | |
| EP1809274B1 (en) | Pharmaceutical composition for rectal or vaginal application comprising a platinum complex | |
| CN101845057B (en) | Substituted phenol for methylal phosphate anesthetic and sedative drugs and preparation method thereof | |
| CN115778896B (en) | Tranexamic acid injection and its preparation method and use | |
| CN103040849A (en) | Tannic acid preparation for treating burn, bedsore and diaper dermatitis and preparation method thereof | |
| CN115969778A (en) | Sulpiride injection for treating mental diseases and preparation method and application thereof | |
| CN104800172A (en) | Carbazochrome sodium sulfonate powder injection for injection and preparation method thereof | |
| CN106176580B (en) | A kind of heat-sensitive gel and preparation method thereof containing matrine alkaloid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170323 Address after: Meilan District 570100 in Hainan province Haikou city Guilin Yang Development Zone (Guilin ocean power station on the right side) Patentee after: Hainan Yi Shun Pharmaceutical Co., Ltd. Address before: 570208 Hainan province Haikou Haidian road two Binjiang coast 4~1701 Patentee before: Chen Changtan |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170605 Address after: 550000 Guizhou city of Guiyang province Zhazuo Xiuwen County Medical Industrial Park, Wanjiang Road Patentee after: Guizhou Jian Ruian Pharmaceutical Co., Ltd. Address before: Meilan District 570100 in Hainan province Haikou city Guilin Yang Development Zone (Guilin ocean power station on the right side) Patentee before: Hainan Yi Shun Pharmaceutical Co., Ltd. |
|
| TR01 | Transfer of patent right |