CN85106763A - 含抗菌氨基糖甙类的复方注射剂制备工艺 - Google Patents
含抗菌氨基糖甙类的复方注射剂制备工艺 Download PDFInfo
- Publication number
- CN85106763A CN85106763A CN85106763.8A CN85106763A CN85106763A CN 85106763 A CN85106763 A CN 85106763A CN 85106763 A CN85106763 A CN 85106763A CN 85106763 A CN85106763 A CN 85106763A
- Authority
- CN
- China
- Prior art keywords
- value
- enteral administration
- preparation technology
- milligrams
- sisomicin
- 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.)
- Withdrawn
Links
- 238000002347 injection Methods 0.000 title claims abstract description 13
- 239000007924 injection Substances 0.000 title claims abstract description 13
- 230000003115 biocidal effect Effects 0.000 title claims abstract description 8
- 229940126575 aminoglycoside Drugs 0.000 title claims abstract description 6
- 150000001875 compounds Chemical class 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229930192786 Sisomicin Natural products 0.000 claims abstract description 9
- 239000002932 luster Substances 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 7
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 6
- URWAJWIAIPFPJE-YFMIWBNJSA-N sisomycin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N URWAJWIAIPFPJE-YFMIWBNJSA-N 0.000 claims abstract description 6
- URWAJWIAIPFPJE-UHFFFAOYSA-N Rickamicin Natural products O1CC(O)(C)C(NC)C(O)C1OC1C(O)C(OC2C(CC=C(CN)O2)N)C(N)CC1N URWAJWIAIPFPJE-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229960000808 netilmicin Drugs 0.000 claims abstract description 5
- ZBGPYVZLYBDXKO-HILBYHGXSA-N netilmycin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@]([C@H](NC)[C@@H](O)CO1)(C)O)NCC)[C@H]1OC(CN)=CC[C@H]1N ZBGPYVZLYBDXKO-HILBYHGXSA-N 0.000 claims abstract description 5
- 229960005456 sisomicin Drugs 0.000 claims abstract description 5
- 230000001105 regulatory effect Effects 0.000 claims abstract description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 3
- 229940088710 antibiotic agent Drugs 0.000 claims abstract description 3
- 150000002148 esters Chemical class 0.000 claims abstract description 3
- 229950007159 etisomicin Drugs 0.000 claims abstract description 3
- 238000001914 filtration Methods 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 230000001954 sterilising effect Effects 0.000 claims abstract description 3
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 3
- 230000008569 process Effects 0.000 claims abstract 4
- 125000003132 pyranosyl group Chemical group 0.000 claims abstract 2
- 239000000243 solution Substances 0.000 claims description 16
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 10
- 235000010265 sodium sulphite Nutrition 0.000 claims description 7
- 239000000470 constituent Substances 0.000 claims description 6
- UXFQFBNBSPQBJW-UHFFFAOYSA-N 2-amino-2-methylpropane-1,3-diol Chemical compound OCC(N)(C)CO UXFQFBNBSPQBJW-UHFFFAOYSA-N 0.000 claims description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 3
- 239000007853 buffer solution Substances 0.000 claims 1
- NCPXQVVMIXIKTN-UHFFFAOYSA-N trisodium;phosphite Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])[O-] NCPXQVVMIXIKTN-UHFFFAOYSA-N 0.000 claims 1
- 239000003708 ampul Substances 0.000 abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 5
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 5
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 5
- 229960002216 methylparaben Drugs 0.000 description 5
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 5
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 5
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- BWRBVBFLFQKBPT-UHFFFAOYSA-N (2-nitrophenyl)methanol Chemical compound OCC1=CC=CC=C1[N+]([O-])=O BWRBVBFLFQKBPT-UHFFFAOYSA-N 0.000 description 3
- CIKNYWFPGZCHDL-ZHFUJENKSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[[(2s,3r)-3-amino-6-(aminomethyl)-3,4-dihydro-2h-pyran-2-yl]oxy]-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;sulfuric acid Chemical group OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N CIKNYWFPGZCHDL-ZHFUJENKSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000006056 electrooxidation reaction Methods 0.000 description 3
- 229960001435 sisomicin sulfate Drugs 0.000 description 3
- CAQWNKXTMBFBGI-UHFFFAOYSA-N C.[Na] Chemical compound C.[Na] CAQWNKXTMBFBGI-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical group [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- 229910021653 sulphate ion Inorganic materials 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- GYYQGTREJKJFLN-UHFFFAOYSA-N S(=O)(O)O.C[Na] Chemical compound S(=O)(O)O.C[Na] GYYQGTREJKJFLN-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007483 microbial process Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 150000003214 pyranose derivatives Chemical group 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明提出制备色泽和pH稳定的非经肠给药注射药剂的工艺过程。该药剂含有氨基糖甙类抗生素，该抗生素结构中有4′和5′间的不饱和键和5′位氨烷基取代的吡喃糖环，较佳者为西梭霉素，乙基西梭霉素或5-表西梭霉素或其非经肠给药可接受的盐类。根据本发明的工艺，活性组分或其盐类溶解于水，调节其pH值为7.3～7.4，加入抗氧化剂，通入氮气过滤，灭菌，然后灌入安瓿。
Description
本发明是关于pH和色泽稳定的非经肠给药复方注射剂的制备工艺。该复方含有在4′和5′位之间为不饱和键，并在5′位有氨烷基取代的吡喃糖环的抗菌的氨基糖甙类，较佳者为西梭霉素（sisomicine），乙基西梭霉素（Netylmicine）或5-表西梭霉素，或其非经肠给药可接受的盐类。制备工艺为：将活性组份或其盐类的水溶液的pH值调节到7.3～7.4之间，加入抗氧化剂，通入氮气，过滤后灭菌，在氮气流和无菌条件下灌入安
。
已知上述氨基糖甙类抗生素存在着某些与pH和色泽稳定性有关的问题，为了解决这些问题，匈牙利专利申请书No.SchE-699提出，将复合物pH值调节到5.0～6.5，最好（但不是必需）加入抗氧化剂。根据该专利，制备稳定注射复方的最佳条件是使其pH值为6.2～6.5。
在研究西梭霉素硫酸盐的不同pH时电化学氧化时发现，随着pH值增大电化学氧化最高电位降低至某一限度。图1，2和3表示西梭霉素硫酸盐作为活性组份，其成份与实例1相同的注射复方电化学氧化时所得的电位值曲线。
曲线表明，pH值较高的注射液最大电位值较小。出乎意料地发现，虽然最大电位值随着pH值增高而降低，调节到较高pH值（pH＝7.3）的西梭霉素注射复方却比pH值较低的要稳定。由上述其它抗生素组成的注射复方也是如此。
本发明的理论基础是：从上述抗生素制备稳定的注射复方，应使其pH值比以前记载的要高。
正常血液或血浆，亦即生理血液和组织的pH值范围为7.3～7.4，本研究工作采用同样的pH值范围。于是，抗生素可在最适宜的pH条件下，即在生理血液的pH下被摄入生物体，从而可以避免从治疗观点看是不必要的作用影响生物体。
根据本发明，含有活性成份西梭霉素（匈牙利专利说明书No.079，145），乙基西梭霉素（匈牙利专利说明书No.170，513）或其类似抗生素、或其有关衍生物的稳定的药剂复方可被制备。
亚磷酸盐或亚硫酸盐可优先选用作抗氧化剂，但任何其它中性或对有机体无害的物系也可用作抗氧化剂。
可加入氢氧化钠和/或缓冲剂调节pH值。下列缓冲剂可优先选用：2-氨基-2-（羟甲基）-1，3-丙二醇缓冲剂，氢氧化钠+磷酸氢钾缓冲剂。
本发明可用下述实例（但不仅限于这些实例）说明：
实施例1
进行以下对比实验，其中
-未调节pH值的西梭霉素硫酸盐溶液（1a），
-匈牙利专利申请书No.SchE-699叙述的，认为是最佳的
pH＝6.2溶液（1b），以及
-按照本发明制备的溶液（1c）
上述三种溶液进行稳定性的比较。
溶液的组成（1毫升溶液中的含量）和制备方式如下
1a）
西梭霉素（以西梭霉素硫酸盐形式） 50.0毫克
甲基亚硫酸氢钠
（Sodium methabisulphite） 3.0毫克
对羟基苯甲酸甲酯 0.8毫克
对羟基苯甲酸丙酯 0.1毫克
乙二胺四乙酸二钠 0.1毫克
氯化钠 3.6毫克
蒸馏水 加至 1.0毫升
1b）
西梭霉素（以西梭霉素硫酸盐形式） 50.0毫克
亚硫酸钠 0.8毫克
甲基亚硫酸氢钠 2.4毫克
对羟基苯甲酸丙酯 0.1毫克
对羟基苯甲酸甲酯 0.8毫克
乙二胺四乙酸二钠 0.1毫克
氯化钠 3.9毫克
蒸馏水 加至 1.0毫升
上述溶液的pH值约为5.2，加入0.1N氢氧化钠溶液，调节其pH值为6.2。
1c）
西梭霉素（以西梭霉素硫酸盐形式） 50.0毫克
亚硫酸钠 0.8毫克
甲基亚硫酸氢钠 2.4毫克
对羟基苯甲酸丙酯 0.1毫克
对羟基苯甲酸甲酯 0.8毫克
乙二胺四乙酸二钠 0.1毫克
氯化钠 3.9毫克
蒸馏水 加至 1.0毫升
所得溶液pH值约为5.2，加入1N氢氧化钠溶液调节其pH值为7.35。将所制得溶液在氮气下装灌。
将上述三种溶液以下法进行稳定性试验：
将测试品在空气恒温箱中于40°，50°和60℃处理30天，然后测定其pH值，色泽和活性组份含量。色泽根据匈牙利药典第六版（Ph.Hg.Ⅵ）方法，与色标比较而测定;用微生物方法测定其生理活性来检测活性组份含量。所得数据列于表1。
从表1可见，测试品1a不耐热，1b的活性组份含量在热处理后无变化，但是其色泽即使经40℃处理也会显著变深;同时其pH值显著降低;在1c的情况下，即使经60℃处理，色泽和含量均在合格范围内，pH值保持不变。
实施例2
含有以下列组分的药剂的制备：
西梭霉素（以硫酸盐形式） 10.0毫克
对羟基苯甲酸丙酯（Ph.Hg.Ⅵ） 0.2毫克
对羟基苯甲酸甲酯（Ph.Hg.Ⅵ） 1.3毫克
乙二胺四乙酸二钠（BP.73） 0.1毫克
亚硫酸钠（BP.80） 1.5毫克
焦亚硫酸钠（Ph.Hg.Ⅵ） 2.5毫克
氯化钠（Ph.Hg.Ⅵ） 4.9毫克
注射用蒸馏水（Ph.Hg.Ⅵ） 加至1.0毫升
所得溶液pH值为5.95，加入2-氨基-2-（羟甲基）-1，3-丙二醇缓冲液使其pH为7.4，通入氮气，所得溶液在无菌条件下用细菌漏斗过滤后，在氮气下灌入安瓿。
上述溶液的色泽、pH和活性成份的稳定性与实例1的1c相当。
实施例3
按照实施例2制备含有下列组分的药剂：
乙基西梭霉素碱（以硫酸盐形式） 50.0毫克
对羟基苯甲酸丙酯（Ph.Hg.Ⅵ） 0.1毫克
对羟基苯甲酸甲酯（Ph.Hg.Ⅵ） 0.8毫克
乙二胺四乙酸二钠（BP.73） 0.1毫克
焦亚硫酸钠（Ph.Hg.Ⅵ） 3.0毫克
亚硫酸钠（BP.80） 4.0毫克
氯化钠（Ph.Hg.Ⅵ） 2.0毫克
注射用蒸馏水 加至1.0毫升
在上述溶液中加入氢氧化钠+硫酸氢钾缓冲液使原pH值由6.2变为7.3，然后按实例2方法制成安瓿剂。
将该溶液在40°，50°和60℃处理30天，其色泽，pH和活性组份的稳定性均为满意。
Claims (3)
1、pH和色泽稳定的非经肠给药注射药剂的制备工艺。该注射复方含有氨基糖甙类抗生素，该抗生素结构中含有在4′和5′位间不饱和键，在5′位有氨烷基取代的吡喃糖环，较佳者为西梭霉素，乙基西梭霉素或5-表西梭霉素或其非经肠给药可接受的盐类。该工艺过程包括：将活性组份或其盐类溶解于水，调节pH值为7.3～7.4，加入抗氧化剂，通入氮气后过滤，消毒，在无菌、通氮下灌装。
2、权利要求1所述的工艺过程，包括使用亚磷酸钠或亚硫酸钠作为抗氧化剂。
3、权利要求1或2所述的工艺过程，包括使用由2-氨基-2-（羟甲基）1，3-丙二醇组成的缓冲体系调节溶液的pH值。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU85859A HU197514B (en) | 1985-03-07 | 1985-03-07 | Process for production of injection sulution containing acid-additional salts od sysomicin |
| HU859/85 | 1985-03-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN85106763A true CN85106763A (zh) | 1987-02-11 |
| CN1010551B CN1010551B (zh) | 1990-11-28 |
Family
ID=10951729
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN85106763A Expired CN1010551B (zh) | 1985-03-07 | 1985-09-09 | 含抗菌氨基糖甙类的复方注射剂制备工艺 |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0195114B1 (zh) |
| JP (1) | JPS61267523A (zh) |
| CN (1) | CN1010551B (zh) |
| AU (1) | AU587014B2 (zh) |
| BE (1) | BE904289A (zh) |
| CA (1) | CA1267091A (zh) |
| DD (1) | DD243208A5 (zh) |
| DE (1) | DE3577657D1 (zh) |
| DK (1) | DK165669C (zh) |
| ES (1) | ES8704078A1 (zh) |
| GB (1) | GB2171907B (zh) |
| GR (1) | GR851869B (zh) |
| HU (1) | HU197514B (zh) |
| IL (1) | IL77958A0 (zh) |
| IT (1) | IT1203543B (zh) |
| LU (1) | LU86343A1 (zh) |
| NL (1) | NL8600480A (zh) |
| PT (1) | PT82144B (zh) |
| SE (1) | SE466384B (zh) |
| SU (1) | SU1440328A3 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115671044A (zh) * | 2022-11-29 | 2023-02-03 | 江苏四环生物制药有限公司 | 一种硫酸奈替米星注射液及其制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3962429A (en) * | 1973-08-01 | 1976-06-08 | Chugai Seiyaku Kabushiki Kaisha | Method for reducing side effects of aminoglycoside antibiotics and composition therefor |
| DE2726208A1 (de) * | 1977-06-10 | 1978-12-21 | Bayer Ag | 1-n-formylsisomicin, verfahren zu seiner herstellung sowie seine verwendung als arzneimittel |
| US4327087A (en) * | 1978-01-16 | 1982-04-27 | Schering Corporation | Stabilized Netilmicin formulations |
| US4223022A (en) * | 1978-01-16 | 1980-09-16 | Schering Corporation | Stabilized aminoglycoside antibiotic formulations |
-
1985
- 1985-03-07 HU HU85859A patent/HU197514B/hu not_active IP Right Cessation
- 1985-07-29 GR GR851869A patent/GR851869B/el unknown
- 1985-07-31 DE DE8585109621T patent/DE3577657D1/de not_active Expired - Fee Related
- 1985-07-31 EP EP85109621A patent/EP0195114B1/en not_active Expired - Lifetime
- 1985-09-09 CN CN85106763A patent/CN1010551B/zh not_active Expired
-
1986
- 1986-02-20 AU AU53845/86A patent/AU587014B2/en not_active Ceased
- 1986-02-21 DD DD86287250A patent/DD243208A5/de unknown
- 1986-02-21 IL IL77958A patent/IL77958A0/xx not_active IP Right Cessation
- 1986-02-26 NL NL8600480A patent/NL8600480A/nl not_active Application Discontinuation
- 1986-02-26 BE BE0/216317A patent/BE904289A/fr not_active IP Right Cessation
- 1986-03-04 IT IT67172/86A patent/IT1203543B/it active
- 1986-03-05 PT PT82144A patent/PT82144B/pt unknown
- 1986-03-06 DK DK101786A patent/DK165669C/da not_active IP Right Cessation
- 1986-03-06 CA CA000503435A patent/CA1267091A/en not_active Expired - Lifetime
- 1986-03-06 SE SE8601050A patent/SE466384B/sv not_active IP Right Cessation
- 1986-03-06 ES ES552709A patent/ES8704078A1/es not_active Expired
- 1986-03-06 LU LU86343A patent/LU86343A1/de unknown
- 1986-03-06 JP JP61049489A patent/JPS61267523A/ja active Granted
- 1986-03-07 SU SU864027095A patent/SU1440328A3/ru active
- 1986-03-07 GB GB8605629A patent/GB2171907B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| IT1203543B (it) | 1989-02-15 |
| EP0195114B1 (en) | 1990-05-16 |
| BE904289A (fr) | 1986-06-16 |
| EP0195114A2 (en) | 1986-09-24 |
| SE466384B (sv) | 1992-02-10 |
| EP0195114A3 (en) | 1988-02-03 |
| NL8600480A (nl) | 1986-10-01 |
| LU86343A1 (fr) | 1986-06-24 |
| SE8601050D0 (sv) | 1986-03-06 |
| HUT40758A (en) | 1987-02-27 |
| ES552709A0 (es) | 1987-04-01 |
| PT82144A (en) | 1986-04-01 |
| DK101786D0 (da) | 1986-03-06 |
| DK101786A (da) | 1986-09-08 |
| DD243208A5 (de) | 1987-02-25 |
| IT8667172A0 (it) | 1986-03-04 |
| AU5384586A (en) | 1986-09-11 |
| IL77958A0 (en) | 1986-08-31 |
| DE3577657D1 (de) | 1990-06-21 |
| JPS61267523A (ja) | 1986-11-27 |
| PT82144B (pt) | 1988-02-17 |
| SU1440328A3 (ru) | 1988-11-23 |
| DK165669B (da) | 1993-01-04 |
| GB8605629D0 (en) | 1986-04-16 |
| JPH0572365B2 (zh) | 1993-10-12 |
| DK165669C (da) | 1993-06-14 |
| SE8601050L (sv) | 1986-09-08 |
| AU587014B2 (en) | 1989-08-03 |
| CN1010551B (zh) | 1990-11-28 |
| GB2171907B (en) | 1989-06-14 |
| HU197514B (en) | 1989-04-28 |
| GB2171907A (en) | 1986-09-10 |
| ES8704078A1 (es) | 1987-04-01 |
| GR851869B (zh) | 1985-12-02 |
| CA1267091A (en) | 1990-03-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1020851C (zh) | 高分子药物的控制释放传递系统 | |
| CN1041793C (zh) | 氟化氯霉素药物组合物 | |
| CA2312558C (en) | Collagen containing tissue adhesive | |
| CN1254247C (zh) | 一种增强抗菌作用的药物组合物 | |
| CN1177300A (zh) | 恩氟沙星注射液或输液 | |
| CN1813739A (zh) | 一种注射用盐酸纳美芬冻干粉针制剂 | |
| CN85106763A (zh) | 含抗菌氨基糖甙类的复方注射剂制备工艺 | |
| CN1698896A (zh) | 注射用复方β－内酰胺类钠盐/丙磺舒钠的制备方法 | |
| CN1803811A (zh) | 一类硝基咪唑衍生物、制备方法及用途 | |
| CN1245987C (zh) | 一种稳定性提高的灯盏花素注射剂及其制备方法 | |
| CN1663999A (zh) | 一种壳聚糖保水凝胶贴剂基质材料及其制备方法 | |
| CN1053569C (zh) | 可注射溶液的制备方法 | |
| CN1438887A (zh) | 水性液体制剂 | |
| CN1046282A (zh) | 抗寄生虫制剂 | |
| CN1090174A (zh) | 甘油烷基醚中的稳定化十六烷基胆碱磷酸溶液 | |
| CN88101780A (zh) | 稳定蛋白质的方法 | |
| CN1228053C (zh) | 含有二尿苷磷酸的滴眼液 | |
| CN1049356C (zh) | 含蛋白质的水质溶液 | |
| CN1193790C (zh) | 胸腺肽组合物注射剂及其制备方法 | |
| CN1830426A (zh) | 一种新鱼腥草素钠注射液及其制备方法和用途 | |
| CN2676917Y (zh) | 壳聚糖药膜 | |
| CN1839842A (zh) | 一种含左西孟旦或其药学上可以接受的盐作为活性成分的药物组合物 | |
| CN1338258A (zh) | 一种抗菌用的克林霉素磷酸酯粉针剂及其制备方法 | |
| CN1398635A (zh) | 具有促思维记忆功能的吡拉西坦药物组合物及其制备方法 | |
| CN1416815A (zh) | 含有前列腺素e1、前列腺素a1和前列腺素b1的复方制剂及其制备方法和用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C13 | Decision | ||
| GR02 | Examined patent application | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |