CN110731967A - 一种门冬氨酸钾镁组合物及其应用 - Google Patents
一种门冬氨酸钾镁组合物及其应用 Download PDFInfo
- Publication number
- CN110731967A CN110731967A CN201911217977.8A CN201911217977A CN110731967A CN 110731967 A CN110731967 A CN 110731967A CN 201911217977 A CN201911217977 A CN 201911217977A CN 110731967 A CN110731967 A CN 110731967A
- Authority
- CN
- China
- Prior art keywords
- potassium
- injection
- stirring
- magnesium aspartate
- liquid medicine
- 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- Withdrawn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
- LVBRFZFUCKKGDJ-HJWRJIQTSA-J magnesium;dipotassium;(2s)-2-aminobutanedioate;hydron Chemical compound [Mg+2].[K+].[K+].OC(=O)[C@@H](N)CC([O-])=O.OC(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC(O)=O.[O-]C(=O)[C@@H](N)CC(O)=O LVBRFZFUCKKGDJ-HJWRJIQTSA-J 0.000 title claims abstract description 32
- 229940111263 potassium magnesium aspartate Drugs 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims abstract description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 36
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 16
- 235000003704 aspartic acid Nutrition 0.000 claims abstract description 16
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000000395 magnesium oxide Substances 0.000 claims abstract description 11
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims abstract description 11
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000002347 injection Methods 0.000 claims description 22
- 239000007924 injection Substances 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 230000001954 sterilising effect Effects 0.000 claims description 21
- 239000007788 liquid Substances 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 239000003708 ampul Substances 0.000 claims description 11
- 239000008215 water for injection Substances 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 9
- 206010003119 arrhythmia Diseases 0.000 claims description 8
- 230000006793 arrhythmia Effects 0.000 claims description 8
- 208000019025 Hypokalemia Diseases 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 208000024896 potassium deficiency disease Diseases 0.000 claims description 7
- 238000004806 packaging method and process Methods 0.000 claims description 6
- 238000001179 sorption measurement Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 208000009525 Myocarditis Diseases 0.000 claims description 3
- 239000003463 adsorbent Substances 0.000 claims description 3
- 239000003610 charcoal Substances 0.000 claims description 3
- 229940105082 medicinal charcoal Drugs 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 206010070863 Toxicity to various agents Diseases 0.000 claims description 2
- 238000009098 adjuvant therapy Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 5
- 238000004659 sterilization and disinfection Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 229910001425 magnesium ion Inorganic materials 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 229910001414 potassium ion Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229920002527 Glycogen Polymers 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229940096919 glycogen Drugs 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229940091250 magnesium supplement Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012982 microporous membrane Substances 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010039020 Rhabdomyolysis Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000003809 bile pigment Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 208000021264 digitalis poisoning Diseases 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000037427 ion transport Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- SWHAQEYMVUEVNF-UHFFFAOYSA-N magnesium potassium Chemical compound [Mg].[K] SWHAQEYMVUEVNF-UHFFFAOYSA-N 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960002363 thiamine pyrophosphate Drugs 0.000 description 1
- 235000008170 thiamine pyrophosphate Nutrition 0.000 description 1
- 239000011678 thiamine pyrophosphate Substances 0.000 description 1
- YXVCLPJQTZXJLH-UHFFFAOYSA-N thiamine(1+) diphosphate chloride Chemical compound [Cl-].CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N YXVCLPJQTZXJLH-UHFFFAOYSA-N 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Inorganic Chemistry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明提供了一种门冬氨酸钾镁组合物,其特征在于由门冬氨酸、氢氧化钾和氧化镁组成,各组分重量份数为:门冬氨酸82‑88份,氢氧化钾15.7‑17.0份,氧化镁6.8‑7.2份。本发明制备的门冬氨酸钾镁组合物稳定性较好。
Description
技术领域
本发明涉及一种门冬氨酸钾镁组合物,具体涉及一种门冬氨酸钾镁组合物及其应用,进一步涉及其在用于低钾血症,洋地黄中毒引起的心律失常以及心肌炎后遗症,充血性心力衰竭,心肌梗塞的辅助治疗,属于医药技术领域。
背景技术
钾离子和镁离子是人体必需的两种微量元素,其特殊的生理功能对维持人体正常新陈代谢十分关键。钾离子在糖元、蛋白质以及高能磷酸化物的合成和分解中具有十分重要的作用,当机体缺钾时,可出现倦怠无力、精神萎靡、烦躁不安,严重缺钾时还会出现心律失常、横纹肌溶解症,以及肾功能障碍,甚至死亡。
镁离子是人体细胞新陈代谢中各种酶系统的活化剂,凡以焦磷酸硫胺为辅因子的酶活化反应均需要镁离子的参与。另外,镁离子也参与核酸合成、碳水化物和脂肪代谢、膜的离子转运、神经冲动的产生等各种生理活动。
门冬氨酸是体内草酰乙酸的前体,在三羧酸循环中起重要作用。同时,门冬氨酸也参加鸟氨酸循环,促进氨和二氧化碳的代谢,使之生成尿素,降低血中氨和二氧化碳的含量。门冬氨酸对细胞亲和力较强,其与钾离子、镁离子结合后,形成稳固的钾盐、镁盐,从而使得门冬氨酸成为钾镁离子的载体使这这两种离子进入机体细胞内。门冬氨酸钾镁参与鸟氨酸循环,使NH3与CO2生成尿素达到解毒作用;它具有以下重要的生理功能:参与三羧酸循环,促进能量代谢,是高能磷酸化合物的合成分解的催化剂;参与核苷酸生成,是细胞修复和再生的重要物质;可促进胆汁及胆色素的排泄,有排黄、减少肝脂肪、增加肝糖原等作用;促进T淋巴细胞发育分化为成熟T淋巴细胞,有抗病毒和抗肿瘤的作用。
现有的门冬氨酸钾镁注射液存在部分杂质,杂质含量高使得注射液质量不易控制,同时高含量的杂质会增大药物不良反应的风险,降低了用药的安全性。
发明内容
本发明的目的是提供一种门冬氨酸钾镁组合物,解决了采用门冬氨酸钾镁注射液稳定性不足的问题,同时还解决了储存过程中原料析出的问题;本发明还提供了其制备方法。
本发明提供的门冬氨酸钾镁组合物,其特征在于门冬氨酸、氢氧化钾和氧化镁组成,各组分重量份数为:
本发明优选的实施方案中,所述的门冬氨酸钾镁组合物各组分重量份数为:
本发明所用原料除了注射用水,只包括门冬氨酸、氢氧化钾、氧化镁,优选用药用炭处理,以吸附其中的杂质,且吸附后除去。优选每10000重量份门冬氨酸钾镁注射液用8-12重量份的药用炭处理。
所述的制备门冬氨酸钾镁注射液的方法,包括以下步骤:
(1)取所配药液总体积80%的注射用水,加入门冬氨酸、氢氧化钾、氧化镁;
(2)搅拌至溶解,调节剂调节pH至6.8-7.2;
(3)加入药用炭,搅拌吸附;
(4)加入剩余的注射用水,搅匀;
(5)过滤;
(6)将过滤后的药液保温储存;
(7)再将药液灌封在安瓿瓶中;
(8)将灌封后的产品进行灭菌和检漏;
(9)灯检、包装。
门冬氨酸钾镁注射液稳定性较差,选择合适工艺参数对门冬氨酸钾镁注射液的稳定性很重要,本发明优选的工艺参数如下:
步骤(1)和(4)注射用水的温度为50-60℃。
步骤(2)pH调节剂选自枸橼酸钠溶液、枸橼酸钾溶液、氢氧化钾溶液、氢氧化钠溶液中的一种,优选氢氧化钠溶液。
步骤(3)药用炭为吸附剂,搅拌吸附后除去;药用炭重量与注射用水总重量的比值为8-12:10000,搅拌吸附时间15min。
步骤(5)中过滤为:先用0.45um的微孔滤膜脱碳,然后经0.22um的微孔滤膜进行除菌过滤。
步骤(6)中的保温储存的温度为25-35摄氏度。
步骤(7)安瓿瓶为中硼硅安瓿瓶。
步骤(8)灭菌温度为121摄氏度,F0值为10-12,灭菌时间为15-20min,冷却温度60-85℃,捡漏下限-80kpa,并保持3min以上。
本发明还提供了一种门冬氨酸组合物用于低钾血症,洋地黄中毒引起的心律失常以及心肌炎后遗症,充血性心力衰竭,心肌梗塞的辅助治疗的应用。通过临床病例疗效观察对比,充分显示了本发明的门冬氨酸钾镁组合物在补充电解质、心脏疾病辅助治疗中相比其他药物的显著优越性。同时本发明制得的门冬氨酸钾镁组合物极大提高了其药物稳定性和安全性。
本发明提供的门冬氨酸钾镁组合物优点如下:
(1)包材使用中硼硅安瓿瓶,能避免因药液与低材质包材长时间接触,浸出未知有害杂质,提高了制剂的稳定性;
(2)选用药用炭作为吸附剂,吸附杂质,且吸附后去除,未使用其他辅料,安全性高。
具体实施方式
以下通过具体实施方式进一步解释或说明本发明内容,但实施例不应被理解为对本发明保护范围的限制。
实施例1门冬氨酸钾镁注射液的制备
处方(1000支):
制备工艺
(1)取所配药液总体积8000ml注射用水,温度50-60℃,加入处方量的门冬氨酸、氢氧化钾、氧化镁;
(2)搅拌至溶解,5mol/l氢氧化钠溶液调节pH至7.0;
(3)加入药用炭10g,搅拌吸附15min;
(4)加入剩余的2000ml注射用水,搅匀;
(5)先用0.45um的微孔滤膜脱碳,然后经0.22um的微孔滤膜进行除菌过滤;
(6)将过滤后的药液25-35℃保温储存;
(7)再将药液灌封在中硼硅安瓿瓶中;
(8)将灌封后的产品进行灭菌和检漏,灭菌温度为121摄氏度,F0值为10-12,灭菌时间为15min,冷却温度60-85℃,捡漏下限-80kpa,并保持3min以上;
(9)灯检、包装。
对比例1门冬氨酸钾镁注射液的制备
处方(1000支):
制备工艺
(1)取所配药液总体积8000ml注射用水,温度40-50℃,加入处方量的门冬氨酸、氢氧化钾、氧化镁;
(2)搅拌至溶解,5mol/l氢氧化钾溶液调节pH至6.5;
(3)加入药用炭8g,搅拌吸附20min;
(4)加入剩余的2000ml注射用水,搅匀;
(5)先用0.45um的微孔滤膜脱碳,然后经0.22um的微孔滤膜进行除菌过滤;
(6)将过滤后的药液25-35℃保温储存;
(7)再将药液灌封在中硼硅安瓿瓶中;
(8)将灌封后的产品进行灭菌和检漏,灭菌温度为121摄氏度,F0值为10-12,灭菌时间为15min,冷却温度60-85℃,捡漏下限-80kpa,并保持3min以上;
(9)灯检、包装。
对比例2门冬氨酸钾镁注射液的制备
处方(1000支):
制备工艺
(1)取所配药液总体积8000ml注射用水,温度50-60℃,加入处方量的门冬氨酸、氢氧化钾、氧化镁;
(2)搅拌至溶解,5mol/l氢氧化钠溶液调节pH至7.4;
(3)加入药用炭12g,搅拌吸附15min;
(4)加入剩余的2000ml注射用水,搅匀;
(5)先用0.45um的微孔滤膜脱碳,然后经0.22um的微孔滤膜进行除菌过滤;
(6)将过滤后的药液25-35℃保温储存;
(7)再将药液灌封在低硼硅安瓿瓶中;
(8)将灌封后的产品进行灭菌和检漏,灭菌温度为121摄氏度,F0值为10-12,灭菌时间为20min,冷却温度60-85℃,捡漏下限-80kpa,并保持3min以上;
(9)灯检、包装。
对比例3门冬氨酸钾镁注射液的制备
处方(1000支):
制备工艺
(1)取所配药液总体积8000ml注射用水,温度40-50℃,加入处方量的门冬氨酸、氢氧化钾、氧化镁;
(2)搅拌至溶解,5mol/l氢氧化钠溶液调节pH至7.1;
(3)加入药用炭12g,搅拌吸附10min;
(4)加入剩余的2000ml注射用水,搅匀;
(5)先用0.45um的微孔滤膜脱碳,然后经0.22um的微孔滤膜进行除菌过滤;
(6)将过滤后的药液40℃保温储存;
(7)再将药液灌封在中硼硅安瓿瓶中;
(8)将灌封后的产品进行灭菌和检漏,灭菌温度为121摄氏度,F0值为10-12,灭菌时间为10min,冷却温度60-85℃,检漏下限-80kpa,并保持3min以上;
(9)灯检、包装。
对比例4
市售的门冬氨酸钾镁注射液,生产厂商浙江瑞新药业股份有限公司,批号20170109。
实施例5:临床试验效果
将60例低钾血症患者随机分为观察组和对照组各30例,观察组使用实施例1门冬氨酸钾镁注射液治疗,对照组使用市售门冬氨酸钾镁注射液治疗,两组疗程均为4天,其余治疗两组均相同,观察两组患者临床症状疗效。
实施例6:临床试验效果
将100例心率失常患者在明确诊断后都施以常规治疗:降糖、降压、扩血管、溶栓。随机分为观察组和对照组各50例,观察组使用实施例1门冬氨酸钾镁注射液治疗,对照组使用市售门冬氨酸钾镁注射液治疗,两组疗程均为7天,其余治疗两组均相同,观察两组患者临床症状疗效。
试验例1结果(性状、酸碱度、门冬氨酸含量、钾含量、镁含量、无菌)
本发明人将实施例1及对比例1~4各例样品进行了加速稳定性考察试验。考察条件为温度40℃±2℃、相对湿度75%±5%。放置6个月,分别于0、1、2、3、6月末取样。考察指标为性状、酸碱度、门冬氨酸含量、钾含量、镁含量。将实施例1及对比例1~4各例样品,结果见下表。
结论:本发明实施例1的样品各项指标均优于对比例1~3制备的样品和市售产品。
试验例2结果(治疗低钾血症疗效)
治疗低钾血症疗效结果
结论:本发明实施例1的样品能够用于低钾血症的治疗,治疗效果明显,优于市售产品。试验例3结果(治疗心律失常疗效)
治疗心律失常疗效结果
组别 | 例数 | 显效 | 有效 | 无效 | 总有效 |
观察组 | 50 | 32(64.0%) | 16(32.0%) | 2(4.0%) | 48(96.0%) |
对照组 | 50 | 19(38.0%) | 23(46.0%) | 8(16.0%) | 42(84.0%) |
结论:本发明实施例1的样品能够用于心律失常的治疗,治疗效果明显,优于市售产品。
本发明的上述描述旨在用作说明,而不是限制。对本领域技术人来说,可以进行本文所述实施方案中的多种变化或修改。在没有脱离本发明的范围或精神内可以得到这些变化。本申请所引用的各个参考文献,在此全文引入作为参考。
Claims (9)
1.一种门冬氨酸钾镁组合物,其特征在于由门冬氨酸、氢氧化钾和氧化镁组成,各组分重量份数为:
3.一种制备权利要求1和2所述门冬氨酸钾镁组合物的方法,其特征在于包括以下步骤:
(1)取所配药液总体积80%的注射用水,加入门冬氨酸、氢氧化钾、氧化镁;
(2)搅拌至溶解,调节剂调节pH至6.8-7.2;
(3)加入药用炭,搅拌吸附;
(4)加入剩余的注射用水,搅匀;
(5)过滤;
(6)将过滤后的药液保温储存;
(7)再将药液灌封在安瓿瓶中;
(8)将灌封后的产品进行灭菌和检漏;
(9)灯检、包装。
4.根据权利要求3所述的制备方法,其特征在于:步骤(1)和(4)注射用水的温度为50-60℃。
5.根据权利要求3所述的制备方法,其特征在于:步骤(2)pH调节剂选自枸橼酸钠溶液、枸橼酸钾溶液、氢氧化钾溶液、氢氧化钠溶液中的一种,优选氢氧化钠溶液。
6.根据权利要求3所述的制备方法,其特征在于:步骤(3)药用炭为吸附剂,搅拌吸附后除去;药用炭重量与注射用水总重量的比值为8-12:10000,搅拌吸附时间15min。
7.根据权利要求3所述的制备方法,其特征在于:步骤(7)安瓿瓶为中硼硅安瓿瓶。
8.根据权利要求3所述的制备方法,其特征在于:步骤(8)灭菌温度为121摄氏度,灭菌时间为15-20min。
9.一种权利要求1和2任一所述的门冬氨酸钾镁组合物在用于低钾血症,洋地黄中毒引起的心律失常以及心肌炎后遗症,充血性心力衰竭,心肌梗塞的辅助治疗的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911217977.8A CN110731967A (zh) | 2019-12-03 | 2019-12-03 | 一种门冬氨酸钾镁组合物及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911217977.8A CN110731967A (zh) | 2019-12-03 | 2019-12-03 | 一种门冬氨酸钾镁组合物及其应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN110731967A true CN110731967A (zh) | 2020-01-31 |
Family
ID=69274286
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911217977.8A Withdrawn CN110731967A (zh) | 2019-12-03 | 2019-12-03 | 一种门冬氨酸钾镁组合物及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110731967A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114732825A (zh) * | 2022-03-14 | 2022-07-12 | 山东德信拓达生物科技研究院有限公司 | 一种畜禽用强心抗应激产品及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1451438A (zh) * | 2003-05-15 | 2003-10-29 | 北京思合友医药科技有限公司 | 一种用木糖醇作等渗调节剂的门冬氨酸钾镁输液 |
RU2229879C1 (ru) * | 2003-02-28 | 2004-06-10 | Закрытое акционерное общество "Биоамид" | Лекарственное средство "аспаркам-l" для регуляции метаболических процессов и способ его получения |
CN105055388A (zh) * | 2015-08-11 | 2015-11-18 | 瑞阳制药有限公司 | 门冬氨酸钾镁注射液及其制备方法 |
CN108969493A (zh) * | 2018-09-06 | 2018-12-11 | 海南通用康力制药有限公司 | 一种注射用门冬氨酸钾镁冻干剂及其制造方法 |
-
2019
- 2019-12-03 CN CN201911217977.8A patent/CN110731967A/zh not_active Withdrawn
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2229879C1 (ru) * | 2003-02-28 | 2004-06-10 | Закрытое акционерное общество "Биоамид" | Лекарственное средство "аспаркам-l" для регуляции метаболических процессов и способ его получения |
CN1451438A (zh) * | 2003-05-15 | 2003-10-29 | 北京思合友医药科技有限公司 | 一种用木糖醇作等渗调节剂的门冬氨酸钾镁输液 |
CN105055388A (zh) * | 2015-08-11 | 2015-11-18 | 瑞阳制药有限公司 | 门冬氨酸钾镁注射液及其制备方法 |
CN108969493A (zh) * | 2018-09-06 | 2018-12-11 | 海南通用康力制药有限公司 | 一种注射用门冬氨酸钾镁冻干剂及其制造方法 |
Non-Patent Citations (3)
Title |
---|
关志宇: "《药物制剂辅料与包装材料》", 31 January 2017, 中国医药科技出版社 * |
凌沛学等: "《药物制剂技术》", 31 May 2017, 中国轻工业出版社 * |
卢健: "《临床药物处方手册》", 31 August 2007, 陕西科学技术出版社 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114732825A (zh) * | 2022-03-14 | 2022-07-12 | 山东德信拓达生物科技研究院有限公司 | 一种畜禽用强心抗应激产品及其制备方法 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109432123B (zh) | 一种复方电解质葡萄糖注射液及其制备方法 | |
EP3854409A1 (en) | Composition for preventing and treating cancer-related fatigue, containing processed ginseng powder or processed ginseng extract having increased ginsenoside constituent | |
CN110731967A (zh) | 一种门冬氨酸钾镁组合物及其应用 | |
CN103040855B (zh) | 一种磷酸氟达拉滨的药物组合物及其制备方法 | |
CN109481459B (zh) | 一种复方电解质葡萄糖注射液及其制备方法 | |
CN102293741B (zh) | 一种盐酸溴己新注射液及其制备方法和用途 | |
CN102462659B (zh) | 一种胞磷胆碱钠注射液及其制备方法 | |
CN109223709B (zh) | 一种果糖二磷酸钠注射液的制备方法 | |
CN103385889A (zh) | 混合糖电解质注射液及其制备方法 | |
CN113209032B (zh) | 注射用门冬氨酸钾镁冻干粉针剂及其制备方法 | |
CN102038680A (zh) | 一种药用组合物 | |
CN109010362A (zh) | 一种小儿复方电解质葡萄糖注射液及其制备方法 | |
CN101518515A (zh) | 注射用三磷酸胞苷二钠冻干粉针剂 | |
CN112315902B (zh) | 一种低易变铁含量蔗糖铁注射液制备方法 | |
CN110563785A (zh) | 一种31/2水三磷酸腺苷二钠化合物 | |
CN100998585A (zh) | 一种盐酸甲氯芬酯注射液的制剂及其制备方法 | |
CN111529485B (zh) | 一种左乙拉西坦注射用浓溶液的制备方法 | |
CN107281135B (zh) | 一种注射用左旋奥拉西坦冻干粉及其制备方法 | |
CN109529016B (zh) | 一种胞磷胆碱钠注射液及其制备方法 | |
CN112168789B (zh) | 一种包含氨基酸的注射用乙酰谷酰胺药物组合物及其应用 | |
CN104645334B (zh) | N‑乙酰半胱氨酸活性炭组合物及其制备方法和应用 | |
CN108158989B (zh) | 一种盐酸氨溴索注射液组合物 | |
CN109381457B (zh) | 一种含14种氨基酸的药物组合物及其制备方法 | |
CN102697742A (zh) | 注射用盐酸头孢唑兰的制备工艺 | |
CN108210451B (zh) | 一种稳定的灯盏花素注射液及其制备工艺 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WW01 | Invention patent application withdrawn after publication | ||
WW01 | Invention patent application withdrawn after publication |
Application publication date: 20200131 |