CN109953983A - 一种葡萄糖酸钙锌口服溶液的制备方法 - Google Patents
一种葡萄糖酸钙锌口服溶液的制备方法 Download PDFInfo
- Publication number
- CN109953983A CN109953983A CN201711424609.1A CN201711424609A CN109953983A CN 109953983 A CN109953983 A CN 109953983A CN 201711424609 A CN201711424609 A CN 201711424609A CN 109953983 A CN109953983 A CN 109953983A
- Authority
- CN
- China
- Prior art keywords
- reagent
- calcium gluconate
- zinc
- preparation
- oral solution
- 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.)
- Pending
Links
- IHBCFWWEZXPPLG-UHFFFAOYSA-N [Ca].[Zn] Chemical compound [Ca].[Zn] IHBCFWWEZXPPLG-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 229940042228 calcium gluconate oral solution Drugs 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims abstract description 15
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims abstract description 15
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims abstract description 13
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003507 refrigerant Substances 0.000 claims abstract description 10
- 239000004227 calcium gluconate Substances 0.000 claims abstract description 9
- 229960004494 calcium gluconate Drugs 0.000 claims abstract description 9
- 235000013927 calcium gluconate Nutrition 0.000 claims abstract description 9
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 claims abstract description 9
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims abstract description 8
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims abstract description 8
- 229960005337 lysine hydrochloride Drugs 0.000 claims abstract description 8
- 239000011670 zinc gluconate Substances 0.000 claims abstract description 7
- 235000011478 zinc gluconate Nutrition 0.000 claims abstract description 7
- 229960000306 zinc gluconate Drugs 0.000 claims abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 239000003153 chemical reaction reagent Substances 0.000 claims description 26
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000009835 boiling Methods 0.000 claims description 11
- 239000000706 filtrate Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 239000008213 purified water Substances 0.000 claims description 9
- 238000005374 membrane filtration Methods 0.000 claims description 7
- 239000004310 lactic acid Substances 0.000 claims description 6
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 3
- 239000000686 essence Substances 0.000 claims description 2
- 244000228451 Stevia rebaudiana Species 0.000 claims 1
- 239000012528 membrane Substances 0.000 claims 1
- 238000001471 micro-filtration Methods 0.000 claims 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 claims 1
- 229930006000 Sucrose Natural products 0.000 abstract description 9
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 abstract description 9
- 239000005720 sucrose Substances 0.000 abstract description 9
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 abstract description 8
- 235000010234 sodium benzoate Nutrition 0.000 abstract description 8
- 239000004299 sodium benzoate Substances 0.000 abstract description 8
- 108010011485 Aspartame Proteins 0.000 abstract description 6
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 abstract description 6
- 239000000605 aspartame Substances 0.000 abstract description 6
- 235000010357 aspartame Nutrition 0.000 abstract description 6
- 229960003438 aspartame Drugs 0.000 abstract description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 abstract description 6
- 239000005711 Benzoic acid Substances 0.000 abstract description 3
- 235000010233 benzoic acid Nutrition 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 239000002671 adjuvant Substances 0.000 abstract 2
- 239000002075 main ingredient Substances 0.000 abstract 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 abstract 1
- 239000003755 preservative agent Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000000022 bacteriostatic agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- AMOYMEBHYUTMKJ-UHFFFAOYSA-N 2-(2-phenylethoxy)ethylbenzene Chemical compound C=1C=CC=CC=1CCOCCC1=CC=CC=C1 AMOYMEBHYUTMKJ-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010006956 Calcium deficiency Diseases 0.000 description 1
- 235000005976 Citrus sinensis Nutrition 0.000 description 1
- 240000002319 Citrus sinensis Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010028034 Mouth ulceration Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical class OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- 208000031320 Teratogenesis Diseases 0.000 description 1
- 208000003217 Tetany Diseases 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- NEEHYRZPVYRGPP-IYEMJOQQSA-L calcium gluconate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O NEEHYRZPVYRGPP-IYEMJOQQSA-L 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 230000001408 fungistatic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000013589 supplement 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
-
- 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
- A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
-
- 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
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
一种葡萄糖酸钙锌口服溶液的制备方法。它主要是解决现有蔗糖含糖量较高、使用了阿司帕坦、苯甲酸或苯甲酸钠等物质的技术问题。其技术方案要点是包括主药及辅药，所述主药包括葡萄糖酸钙、葡萄糖酸锌与盐酸赖氨酸，其特征在于，所述辅药中含有甜菊素、清凉醇与羟苯乙酯。它主要是应用于医药技术领域。
Description
技术领域
本发明属于医药技术领域，尤其涉及一种补钙、锌用的口服溶液及其制备方法。
背景技术
葡萄糖酸钙锌口服溶液是一种已上市药物，适应症为因缺钙、锌引起的疾病，包括骨质疏松、手足抽搐症、佝偻病、妊娠妇女、哺乳期妇女和绝经期妇女补充钙质，以及小儿生长发育迟缓、食欲缺乏、厌食症、复发性口腔溃疡以及痤疮等。其传统处方为：葡萄糖酸钙60g、葡萄糖酸锌3g、盐酸赖氨酸10g、蔗糖100g、氯化钠0.1g、香精1.2g、氢氧化钠适量、纯化水加至1000ml。近年来有研究对处方进行了改良，将处方中的矫味剂改为单用阿斯巴甜、安赛蜜或将阿斯巴甜、安赛蜜混合使用，并添加苯甲酸或苯甲酸钠作为防腐剂。
上述改良后的葡萄糖酸钙锌口服溶液依然存在如下缺点：（1）蔗糖含糖量较高，可能导致儿童蛀牙、妊娠期高血糖以及老年糖尿病，另外，蔗糖含糖量高会导致溶液粘度较大，微孔滤膜过滤缓慢，生产效率低；还有，蔗糖含糖量较高导致葡萄糖酸钙在口服溶液中呈过饱和状态，易结晶析出，稳定性差。（2）使用了阿司帕坦、苯甲酸或苯甲酸钠等物质，虽然这几种物质的处方添加量符合国家标准，但也有实验研究证明阿司帕坦、苯甲酸钠具有一定的生理毒性。
发明内容
本发明所要解决的技术问题是克服以上背景技术中提到的不足和缺陷，提供一种不含蔗糖、安全性高的葡萄糖酸钙锌口服溶液，并相应提供其制备方法。为解决上述技术问题，本发明提出的技术方案为：
本发明包括葡萄糖酸钙、葡萄糖酸锌、盐酸赖氨酸、乳酸、甜菊素、清凉醇、羟苯乙酯、香精、氢氧化钠、纯化水，其制备方法如下：
（1）将纯化水煮沸后加入葡萄糖酸钙，并保持沸腾10min得到试剂1；
（2）在步骤（1）中得到的试剂1中加入葡萄糖酸锌、盐酸赖氨酸、甜菊素与清凉醇，并保持沸腾40min得到的试剂2；
（3）在步骤（2）中得到的试剂2中加入羟苯乙酯，并保持沸腾5min，冷却至40℃后得到的试剂3；
（4）在步骤（3）中得到的试剂3中加入乳酸与香精，再加入剩余的纯化水，用氢氧化钠调节pH得到的试剂4；
（5）将步骤（4）中得到的试剂4用微滤膜过滤，收集滤液得到葡萄糖酸钙锌口服溶液。
本发明用氢氧化钠调pH至4.0-5.0。
本发明的微滤膜过滤时，将所述试剂4依次用0.8um、0.45um的微滤膜过滤。
本发明的甜菊素、香精与清凉醇的重量比为6：6：7。
本发明中使用甜菊素代替蔗糖，甜菊素的甜度是蔗糖的约300倍，不被人体吸收，不产生热量，不与体内脂肪发生相互作用，故可以在保持成品口感的同时不引起血糖波动，对于发育期儿童、妊娠期妇女以及老年人均不会引起相关方面的副作用。本发明中使用羟苯乙酯代替苯甲酸钠等常规防腐剂，有研究证明苯甲酸钠的用量和小鼠精子致畸数呈正相关关系，而羟苯酯类防腐剂的主要不良反应集中在过敏反应，尤其是在皮肤破损处的局部外用方面，因此，从严重程度上说，羟苯乙酯比苯甲酸钠更加安全，利用羟苯乙酯得到的葡萄糖酸钙锌口服溶液产品的安全性更高。
与现有技术相比，本发明的优点在于：
1、本发明使用甜菊素代替阿斯巴甜/蔗糖，在取得更好的口感的同时降低了药物对人体血糖浓度的影响，也降低了辅料带来的安全风险；另外，本发明中由于不含有高浓度的蔗糖，溶液粘度低，利用微滤膜过滤时，过滤速度快。
2、本发明使用羟苯乙酯代替苯甲酸钠等常规防腐剂，葡萄糖酸钙锌口服溶液的安全性的方面有较大提升。
具体实施方式
实施例1.一种葡萄糖酸钙锌口服溶液中，包括以下重量份的组分：
葡萄糖酸钙 600份；
葡萄糖酸锌 30份；
盐酸赖氨酸 100份；
乳酸 120份；
甜菊素 10份；
清凉醇 10份；
羟苯乙酯 5份；
香精 10份；
氢氧化钠 适量（调节pH至4.0-5.0所需要的用量）；
纯化水 10000份。
上述葡萄糖酸钙锌口服溶液的制备方法，包括以下步骤：
（1）将8L纯化水煮沸20min后加入葡萄糖酸钙，并保持沸腾10min得到试剂1；
（2）在步骤（1）中得到的试剂1中加入葡萄糖酸锌、盐酸赖氨酸、甜菊素与清凉醇，并保持沸腾40min得到的试剂2；
（3）在步骤（2）中得到的试剂2中加入羟苯乙酯，并保持沸腾5min，冷却至40℃后得到的试剂3；
（4）在步骤（3）中得到的试剂3中加入乳酸与香精，再加入剩余的纯化水，用氢氧化钠调节pH至4.0-5.0得到的试剂4；
（5）将步骤（4）中得到的试剂4依次用0.8um、0.45um的微滤膜过滤，收集滤液用10mL棕色玻璃瓶灌装/封瓶。
实施例2-4：
实施例2-4的配方组分与制备方法与实施例1相同，不同之处在于甜菊素、羟苯乙酯与香精用量有所不同，具体用量参见表1。
将利用实施例1-4中的配方得到的葡萄糖酸钙锌口服溶液进行口感与香味测试，结果如下表1所示。
表1：不同用量的甜菊素、羟苯乙酯与香精的实验结果（重量份）
上表中，香精包括但不仅限于苹果味香精、甜橙汁味香精。由上表的实验结果可以看出，甜菊素、香精与清凉醇的重量比为12：12：14实验效果最好。
实施例5-8：
实施例5-8的配方组分与制备方法与实施例1相同，不同之处在于羟苯乙酯的用量有所不同，具体用量参见表2。
将利用实施例5-8中的配方得到的葡萄糖酸钙锌口服溶液进行抑菌效力试验，结果如下表2所示。
表2：不同用量的羟苯乙酯的抑菌效力试验菌数下降lg值（重量份）
抑菌效力试验时，取抑菌力试验用供试品10ml，加pH7.0无菌氯化钠-蛋白胨缓冲液至100ml，制成1：10的供试液。准备5份供试品、空白口服液溶液、稀释剂。每一份待测溶液接种一个试验菌，取供试品适量，分别转移至5个适宜的无菌容器中，每一容器接种一种试验菌，1ml接种菌量为105～106cfu，接种菌液的体积不得超过供试品体积的0.5%～1%，充分混合，使供试品中的试验菌均匀分布。然后将接种的供试品在试验期间置20～25℃，避光贮存，贮存温度的变化应尽可能控制在最小范围，并防止被污染。不同浓度的防腐剂平行配置，每份样品平行操作三次。
由上表2可知，用实施例7中重量份的羟苯乙酯作为抑菌剂，保证抑菌效果的同时还可尽量减少抑菌剂的使用。
抑菌效力判断依据：
注：NI:未增加，是指对前一个测定时间，试验菌增加的数量不超过0.5lg。
Claims (4)
1.一种葡萄糖酸钙锌口服溶液的制备方法，其特征在于，包括葡萄糖酸钙、葡萄糖酸锌、盐酸赖氨酸、乳酸、甜菊素、清凉醇、羟苯乙酯、香精、氢氧化钠、纯化水，其制备方法如下：
（1）将纯化水煮沸后加入葡萄糖酸钙，并保持沸腾10min得到试剂1；
（2）在步骤（1）中得到的试剂1中加入葡萄糖酸锌、盐酸赖氨酸、甜菊素与清凉醇，并保持沸腾40min得到的试剂2；
（3）在步骤（2）中得到的试剂2中加入羟苯乙酯，并保持沸腾5min，冷却至40℃后得到的试剂3；
（4）在步骤（3）中得到的试剂3中加入乳酸与香精，再加入剩余的纯化水，用氢氧化钠调节pH得到的试剂4；
（5）将步骤（4）中得到的试剂4用微滤膜过滤，收集滤液得到葡萄糖酸钙锌口服溶液。
2.根据权利要求1所述的葡萄糖酸钙锌口服溶液的制备方法，其特征在于，用氢氧化钠调pH至4.0-5.0。
3.根据权利要求1所述的葡萄糖酸钙锌口服溶液的制备方法，其特征在于，所述微滤膜过滤时，将所述试剂4依次用0.8um、0.45um的微滤膜过滤。
4.根据权利要求1所述的葡萄糖酸钙锌口服溶液的制备方法，其特征在于，所述甜菊素、香精与清凉醇的重量比为6：6：7。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711424609.1A CN109953983A (zh) | 2017-12-26 | 2017-12-26 | 一种葡萄糖酸钙锌口服溶液的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711424609.1A CN109953983A (zh) | 2017-12-26 | 2017-12-26 | 一种葡萄糖酸钙锌口服溶液的制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109953983A true CN109953983A (zh) | 2019-07-02 |
Family
ID=67021217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711424609.1A Pending CN109953983A (zh) | 2017-12-26 | 2017-12-26 | 一种葡萄糖酸钙锌口服溶液的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109953983A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113262202A (zh) * | 2021-06-30 | 2021-08-17 | 江西益佰年药业股份有限公司 | 一种葡萄糖酸钙锌口服液的制备工艺方法 |
-
2017
- 2017-12-26 CN CN201711424609.1A patent/CN109953983A/zh active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113262202A (zh) * | 2021-06-30 | 2021-08-17 | 江西益佰年药业股份有限公司 | 一种葡萄糖酸钙锌口服液的制备工艺方法 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2931268T3 (en) | GAMMA HYDROXYBUTYRATE COMPOSITIONS AND THEIR USE FOR THE TREATMENT OF DISEASES | |
| CN104800261B (zh) | 一种丁香复方漱口水 | |
| CN104621296B (zh) | 一种具有调节血脂、血糖、血压功能的中药组合茶饮料 | |
| CA1305057C (en) | Calcium salts | |
| CN1433304A (zh) | 睡眠促进用组合物 | |
| US20100317604A1 (en) | Forsythiaside injection preparation and preparative method thereof | |
| CN101642277A (zh) | 一种葛根仙人掌保健饮料及其制备方法 | |
| AU2021106210B4 (en) | Isotopic compositions | |
| CN109953983A (zh) | 一种葡萄糖酸钙锌口服溶液的制备方法 | |
| CN101244071A (zh) | 一种果糖二磷酸钠注射液的制备方法 | |
| CN109953980A (zh) | 一种葡萄糖酸钙锌口服溶液及其制备方法 | |
| CN109953947A (zh) | 葡萄糖酸钙锌口服溶液及其制备方法 | |
| CN106539086A (zh) | 一种改善视力的蓝莓花青素口服液及其制备方法 | |
| CN102178292A (zh) | 对化学肝损伤有保护作用的籽瓜汁系列制品 | |
| CN109528644A (zh) | 一种葡萄糖酸钙锌口服溶液及其制备方法 | |
| CN107898809A (zh) | 一种葡萄糖酸钙锌口服溶液及其制备方法 | |
| RU2473357C2 (ru) | Жидкая композиция, повышающая работоспособность и обладающая адаптогенным, ранозаживляющим, противовоспалительным действием | |
| CN107550896A (zh) | 一种蒜氨酸组合物 | |
| CN103505408A (zh) | 一种奥拉西坦葡萄糖/氯化钠注射液的制备方法 | |
| KR20120093635A (ko) | 장염 예방 또는 치료용 약학 조성물 | |
| CN1105213A (zh) | 罐装甘麦大枣汤 | |
| CN112472733A (zh) | 一种促进钙口服吸收的葛花提取物 | |
| KR101538055B1 (ko) | 우르시올이 제거된 옻 추출물의 제조방법 및 상기 방법으로 제조된 옻 추출물의 약침으로서의 용도 | |
| RU2313350C1 (ru) | Способ повышения растворимости кальция сукцината, кальция малата и кальция цитрата для детских лекарственных форм | |
| CN114712436B (zh) | 一种抗幽门螺旋杆菌的复合物及其制备方法和应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190702 |
|
| WD01 | Invention patent application deemed withdrawn after publication |