CN112190575A - Calcium zinc gluconate oral solution and preparation method thereof - Google Patents
Calcium zinc gluconate oral solution and preparation method thereof Download PDFInfo
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- CN112190575A CN112190575A CN202011153545.8A CN202011153545A CN112190575A CN 112190575 A CN112190575 A CN 112190575A CN 202011153545 A CN202011153545 A CN 202011153545A CN 112190575 A CN112190575 A CN 112190575A
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- zinc gluconate
- oral solution
- calcium zinc
- temperature
- calcium
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- 239000011670 zinc gluconate Substances 0.000 title claims abstract description 49
- 235000011478 zinc gluconate Nutrition 0.000 title claims abstract description 49
- 229960000306 zinc gluconate Drugs 0.000 title claims abstract description 49
- 229940100688 oral solution Drugs 0.000 title claims abstract description 45
- IHBCFWWEZXPPLG-UHFFFAOYSA-N [Ca].[Zn] Chemical compound [Ca].[Zn] IHBCFWWEZXPPLG-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title abstract description 22
- 239000004227 calcium gluconate Substances 0.000 claims abstract description 26
- 229960004494 calcium gluconate Drugs 0.000 claims abstract description 26
- 235000013927 calcium gluconate Nutrition 0.000 claims abstract description 26
- 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 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000008213 purified water Substances 0.000 claims abstract description 15
- 239000004376 Sucralose Substances 0.000 claims abstract description 12
- 235000019408 sucralose Nutrition 0.000 claims abstract description 12
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims abstract description 12
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims abstract description 10
- 229960005337 lysine hydrochloride Drugs 0.000 claims abstract description 10
- 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 9
- 235000006040 Prunus persica var persica Nutrition 0.000 claims abstract description 8
- 239000004310 lactic acid Substances 0.000 claims abstract description 8
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 8
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims abstract description 8
- 235000010234 sodium benzoate Nutrition 0.000 claims abstract description 8
- 239000004299 sodium benzoate Substances 0.000 claims abstract description 8
- 240000006413 Prunus persica var. persica Species 0.000 claims abstract 2
- 239000007788 liquid Substances 0.000 claims description 45
- 238000003756 stirring Methods 0.000 claims description 36
- 239000000463 material Substances 0.000 claims description 31
- 238000010438 heat treatment Methods 0.000 claims description 27
- 229920003023 plastic Polymers 0.000 claims description 18
- 239000004033 plastic Substances 0.000 claims description 18
- 238000001914 filtration Methods 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 10
- 239000003708 ampul Substances 0.000 claims description 8
- 229920001684 low density polyethylene Polymers 0.000 claims description 8
- 239000004702 low-density polyethylene Substances 0.000 claims description 8
- 229920000728 polyester Polymers 0.000 claims description 8
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 7
- 238000005538 encapsulation Methods 0.000 claims description 7
- 239000005022 packaging material Substances 0.000 claims description 7
- 229960003885 sodium benzoate Drugs 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 2
- 238000011534 incubation Methods 0.000 claims 1
- 230000006641 stabilisation Effects 0.000 claims 1
- 238000011105 stabilization Methods 0.000 claims 1
- 108010011485 Aspartame Proteins 0.000 abstract description 12
- 239000000605 aspartame Substances 0.000 abstract description 12
- 235000010357 aspartame Nutrition 0.000 abstract description 12
- 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 12
- 229960003438 aspartame Drugs 0.000 abstract description 12
- 229930006000 Sucrose Natural products 0.000 abstract description 10
- 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 10
- 239000005720 sucrose Substances 0.000 abstract description 10
- 235000019640 taste Nutrition 0.000 abstract description 5
- 229960000448 lactic acid Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 24
- 239000000047 product Substances 0.000 description 19
- 238000011049 filling Methods 0.000 description 15
- 239000013065 commercial product Substances 0.000 description 10
- 238000011068 loading method Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 9
- 235000003599 food sweetener Nutrition 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000003765 sweetening agent Substances 0.000 description 8
- 239000012535 impurity Substances 0.000 description 7
- 238000007689 inspection Methods 0.000 description 7
- 244000144730 Amygdalus persica Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000004698 Polyethylene Substances 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 238000000071 blow moulding Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 230000000813 microbial effect Effects 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 229960005069 calcium Drugs 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
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- 238000001556 precipitation Methods 0.000 description 3
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- 238000011160 research Methods 0.000 description 3
- NOEGNKMFWQHSLB-UHFFFAOYSA-N 5-hydroxymethylfurfural Chemical compound OCC1=CC=C(C=O)O1 NOEGNKMFWQHSLB-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 206010006956 Calcium deficiency Diseases 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical class O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 229940069978 calcium supplement Drugs 0.000 description 2
- 208000002925 dental caries Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- RJGBSYZFOCAGQY-UHFFFAOYSA-N hydroxymethylfurfural Natural products COC1=CC=C(C=O)O1 RJGBSYZFOCAGQY-UHFFFAOYSA-N 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 238000004382 potting Methods 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000019614 sour taste Nutrition 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 235000019605 sweet taste sensations Nutrition 0.000 description 2
- 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
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 208000007117 Oral Ulcer Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000003217 Tetany Diseases 0.000 description 1
- 206010048259 Zinc deficiency Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229960005164 acesulfame Drugs 0.000 description 1
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 208000002399 aphthous stomatitis Diseases 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000009508 confectionery Nutrition 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
- 238000011161 development Methods 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 238000013441 quality evaluation Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
- 108010048734 sclerotin Proteins 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
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- 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
-
- 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
- A61K47/26—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a calcium zinc gluconate oral solution and a preparation method thereof, wherein the calcium zinc gluconate oral solution is composed of calcium gluconate, zinc gluconate, lysine hydrochloride, lactic acid, sucralose, sodium benzoate, juicy peach essence and purified water. The calcium zinc gluconate oral solution does not contain sucrose or aspartame, has good taste and good stability, and has the advantage of simple preparation process.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to calcium zinc gluconate oral solution and a preparation method thereof.
Background
The calcium zinc gluconate oral solution is a calcium zinc compound product which is firstly developed by the pharmaceutical company of Auno (China), mainly comprises calcium gluconate, zinc gluconate and lysine hydrochloride, and is used for treating diseases caused by calcium deficiency and zinc deficiency, such as osteoporosis, tetany, bone hypoplasia, rickets, calcium supplement for pregnant women and lactating women, infantile growth and development retardation, anorexia, recurrent oral ulcer, acne and the like. The calcium component contained in the medicine is provided for normal physiological needs of human bodies together with calcium obtained from food, the lysine is combined to nourish bones to keep healthy and tough sclerotin, the misarea of single calcium supplement due to calcium deficiency is removed, the problem of supplement of mineral substances, trace elements and other nutrients is solved, and the problems of multiple contents of most calcium preparations in the market, slight absorption and bioavailability and the like are solved.
In a product sold in research and market, a sweetening agent is generally sucrose or a combined sweetening agent of aspartame and acesulfame, wherein sucrose is easy to grow bacteria due to low sweetness and large using amount, and a sucrose-containing preparation causes tooth decay of children, hyperglycemia in gestation period and senile diabetes and is not suitable for diabetics; in addition, the sucrose used as a sweetening agent causes high solution viscosity, slow filtration speed and low production efficiency, and the filter stick needs to be frequently replaced, thereby affecting the content of the main drug in the product. For the aspartame and acesulfame potassium combined sweetener, aspartame is prepared by the chemical or enzymatic reaction of L-phenylalanine and L-aspartic acid, and is easy to degrade under the high temperature condition, so that the sweetness in vivo is seriously reduced after high-temperature sterilization, and related substances in the solution are correspondingly increased. The Chinese invention patent CN201310628801.8 discloses that aspartame is adopted as a sweetening agent in calcium zinc gluconate oral solution, the problem of impurities generated by high-temperature degradation of aspartame cannot be solved, sodium chloride is contained in the formula, and the pH value is adjusted by sodium hydroxide, so that the product has certain salinity and the taste of people is affected. The Chinese patent CN201510133281.2 does not solve the problem of aspartame degradation, does not control the pH value of the calcium zinc gluconate oral solution, and cannot guarantee the quality of the product.
The solubility of calcium gluconate is about 40mg/ml at room temperature, and the calcium gluconate content in the commercial products is 60mg/ml and is in a supersaturated state, so that the solution stability is poor, and the precipitated calcium gluconate solid is in a scale state. To alleviate this problem, the compound of the pharmaceutical company, australian, No. (chinese) has a patent No. cn201310111514.x, which keeps the material in boiling water at 100 ℃ to be heated, refluxed and dissolved, so that the stability of lysine hydrochloride and flavoring agent in the solution is affected, and the production efficiency is low. The Chinese patent CN201811625872.1 added with surfactant as solubilizer and adjusted pH value with sodium hydroxide, and has no study on the safety of introducing surfactant.
It can be seen that although the prior art has made some improvements to the above disadvantages, a plurality of chinese patents disclose various formulations and/or preparation processes of calcium zinc gluconate oral solutions, none of them completely solve the above problems.
The sucralose is used as a novel sweetener, has the sweetness of 600-800 times that of the sucrose, has stable property, no peculiar smell and no toxic or side effect, is a perfect and competitive new-generation sweetener developed by people so far, and is an ideal sweet substitute for diabetes mellitus. The invention provides a calcium zinc gluconate oral solution without sucrose or aspartame through research. In order to overcome the defects that the calcium zinc gluconate oral solution is a supersaturated solution, the solution system is unstable and crystal nucleus is easy to form to precipitate crystals, therefore, the inventor carries out research on the preparation process and finally successfully obtains an excellent oral solution formula and a preparation method.
Disclosure of Invention
The invention aims to provide a calcium zinc gluconate oral solution and a preparation method thereof, which do not contain sucrose or aspartame, have good stability and simple preparation process and solve the problems of sweetener selection and preparation stability in the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a calcium zinc gluconate oral solution, which comprises the following components:
preferably, the pH value of the calcium zinc gluconate oral solution is controlled within the range of 3.5-4.5. Therefore, the calcium gluconate can not be crystallized in a low-temperature environment, and the solution stability is good.
More preferably, the pH value control range of the calcium zinc gluconate oral solution is 3.8-4.0, and the system stability is good.
In a second aspect, the present invention provides a preparation method of the above calcium zinc gluconate oral solution, comprising the following steps:
(1) adding 90% of purified water into a mixing tank, heating to a certain temperature, adding weighed calcium gluconate, and stirring until the calcium gluconate is dissolved;
(2) maintaining the heating temperature, sequentially adding zinc gluconate, lysine hydrochloride, sodium benzoate, sucralose and lactic acid into the material obtained in the step (1), and stirring until the materials are dissolved;
(3) heating to a certain temperature, keeping the temperature for 10-30 minutes, and stopping heating;
(4) and (4) cooling the material obtained in the step (3) to a temperature lower than 40 ℃, adding juicy peach essence, adding purified water to full volume, fixing the volume, uniformly stirring, filtering, and encapsulating.
Preferably, in the step (1), the heating temperature is 80-90 ℃.
Preferably, in the step (2), the heating stabilizing temperature is 80-90 ℃.
Preferably, in the step (3), the heat preservation temperature is 100-110 ℃. Therefore, residual calcium gluconate crystal nuclei in the system can be effectively eliminated, and the precipitation of calcium gluconate is prevented.
Preferably, in the filtering in the step (4), the material is filtered through a 0.45 μm titanium rod filter.
Preferably, in step (4), the potting packaging material used for potting is a plastic ampoule made of polyester/low density polyethylene oral liquid pharmaceutical hard sheet.
Compared with the prior art, the invention provides the calcium zinc gluconate oral solution and the preparation method thereof, and the calcium zinc gluconate oral solution has the following beneficial effects:
1. the sucralose is used for replacing sucrose or aspartame, so that the taste is good, the preparation is not easy to generate impurities due to the degradation of auxiliary materials, the safety risk caused by the auxiliary materials is reduced, children's tooth decay, hyperglycemia in gestation period and senile diabetes are not easy to cause, and the sucralose-containing oral liquid is suitable for diabetics; in addition, the invention has low solution viscosity, high filtering speed of the 0.45 mu m microporous filter membrane, high production efficiency and good process robustness because the high-concentration sucrose is not contained;
2. according to the invention, the high-temperature heat preservation operation at the temperature of more than 100 ℃ is adopted, residual calcium gluconate crystal nuclei in the system are effectively eliminated, the precipitation of calcium gluconate is prevented, in addition, the pH value of the finished product is controlled to be 3.5-4.5, the calcium gluconate is further ensured not to precipitate crystals in a low-temperature environment, and the solution stability is good;
3. the invention adopts the packing form of the plastic ampoule made of the polyester/low-density polyethylene oral liquid hard tablet, greatly reduces the packing cost and the transportation cost, and greatly improves the use safety compared with the packing of a glass oral liquid bottle.
Detailed Description
The technical solutions of the present invention will be described clearly and completely by the detailed embodiments, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
The embodiment provides a calcium zinc gluconate oral solution, which comprises the following components in part by weight:
the preparation method of the calcium zinc gluconate oral solution comprises the following steps:
(1) adding purified water with the amount of 90% of the prescription amount into the batching tank, starting a stirring device and a steam valve, heating to 85 ℃, maintaining at 85 ℃, adding weighed calcium gluconate, and stirring for 15 minutes until the calcium gluconate is completely dissolved.
(2) And (2) maintaining the heating temperature at 85 ℃, adding zinc gluconate, lysine hydrochloride, sodium benzoate, sucralose and lactic acid into the material obtained in the step (1) in sequence, and stirring for 15 minutes until the materials are completely dissolved.
(3) The temperature of the liquid medicine is continuously heated to 105 ℃ and kept for 30 minutes, and then the steam valve is closed to stop heating.
(4) And (3) starting the condensed water, continuing stirring, cooling, stopping stirring until the temperature of the material is lower than 40 ℃, continuing adding purified water into the batching tank to full volume after adding the juicy peach essence, fixing the volume, and stirring for 15 minutes until the material is uniform.
(5) And filtering the prepared liquid medicine by a 0.45-micrometer titanium rod filter, transferring the liquid medicine into a liquid storage tank, and detecting the pH value of the liquid medicine, wherein the pH value is within a qualified range of 3.5-4.5, and the preferred pH value is 3.8-4.0. And after the oral liquid is detected to be qualified, filling the mixture by using an automatic forming filling and sealing machine for the oral liquid plastic bottle, wherein the selected packaging material is a plastic ampoule made of a polyester/low-density polyethylene oral liquid hard sheet (PET/PE). The loading amount is set to be 10.3ml, and the control range of the loading amount is 10.1 ml/piece to 10.3 ml/piece. And (4) qualified encapsulation standard: the seal is symmetrical, the blow molding protruding part is symmetrical, the plastic panel is flat and dense, and the filling amount is not less than 10.0 ml/piece. And finally, performing light inspection on the qualified filled sample, removing the leaked oral solution, and packaging.
Example 2
The embodiment provides a calcium zinc gluconate oral solution, which comprises the following components in part by weight:
the preparation method of the calcium zinc gluconate oral solution comprises the following steps:
(1) adding purified water with the amount of 90% of the prescription amount into the batching tank, starting a stirring device and a steam valve, heating to 85 ℃, maintaining at 85 ℃, adding weighed calcium gluconate, and stirring for 15 minutes until the calcium gluconate is completely dissolved.
(2) And (2) maintaining the heating temperature at 85 ℃, adding zinc gluconate, lysine hydrochloride, sodium benzoate, sucralose and lactic acid into the material obtained in the step (1) in sequence, and stirring for 15 minutes until the materials are completely dissolved.
(3) The temperature of the liquid medicine is continuously heated to 105 ℃ and kept for 30 minutes, and then the steam valve is closed to stop heating.
(4) And (3) starting the condensed water, continuing stirring, cooling, stopping stirring until the temperature of the material is lower than 40 ℃, continuing adding purified water into the batching tank to full volume after adding the juicy peach essence, fixing the volume, and stirring for 15 minutes until the material is uniform.
(5) And filtering the prepared liquid medicine by a 0.45-micrometer titanium rod filter, transferring the liquid medicine into a liquid storage tank, and detecting the pH value of the liquid medicine, wherein the pH value is within a qualified range of 3.5-4.5, and the preferred pH value is 3.8-4.0. And after the oral liquid is detected to be qualified, filling the mixture by using an automatic forming filling and sealing machine for the oral liquid plastic bottle, wherein the selected packaging material is a plastic ampoule made of a polyester/low-density polyethylene oral liquid hard sheet (PET/PE). The loading amount is set to be 10.3ml, and the control range of the loading amount is 10.1 ml/piece to 10.3 ml/piece. And (4) qualified encapsulation standard: the seal is symmetrical, the blow molding protruding part is symmetrical, the plastic panel is flat and dense, and the filling amount is not less than 10.0 ml/piece. And finally, performing light inspection on the qualified filled sample, removing the leaked oral solution, and packaging.
Example 3
The embodiment provides a calcium zinc gluconate oral solution, which comprises the following components in part by weight:
the preparation method of the calcium zinc gluconate oral solution comprises the following steps:
(1) adding purified water with the amount of 90% of the prescription amount into the batching tank, starting a stirring device and a steam valve, heating to 85 ℃, maintaining at 85 ℃, adding weighed calcium gluconate, and stirring for 15 minutes until the calcium gluconate is completely dissolved.
(2) And (2) maintaining the heating temperature at 85 ℃, adding zinc gluconate, lysine hydrochloride, sodium benzoate, sucralose and lactic acid into the material obtained in the step (1) in sequence, and stirring for 15 minutes until the materials are completely dissolved.
(3) The temperature of the liquid medicine is continuously heated to 105 ℃ and kept for 30 minutes, and then the steam valve is closed to stop heating.
(4) And (3) starting the condensed water, continuing stirring, cooling, stopping stirring until the temperature of the material is lower than 40 ℃, continuing adding purified water into the batching tank to full volume after adding the juicy peach essence, fixing the volume, and stirring for 15 minutes until the material is uniform.
(5) And filtering the prepared liquid medicine by a 0.45-micrometer titanium rod filter, transferring the liquid medicine into a liquid storage tank, and detecting the pH value of the liquid medicine, wherein the pH value is within a qualified range of 3.5-4.5, and the preferred pH value is 3.8-4.0. And after the oral liquid is detected to be qualified, filling the mixture by using an automatic forming filling and sealing machine for the oral liquid plastic bottle, wherein the selected packaging material is a plastic ampoule made of a polyester/low-density polyethylene oral liquid hard sheet (PET/PE). The loading amount is set to be 10.3ml, and the control range of the loading amount is 10.1 ml/piece to 10.3 ml/piece. And (4) qualified encapsulation standard: the seal is symmetrical, the blow molding protruding part is symmetrical, the plastic panel is flat and dense, and the filling amount is not less than 10.0 ml/piece. And finally, performing light inspection on the qualified filled sample, removing the leaked oral solution, and packaging.
Example 4
The embodiment provides a calcium zinc gluconate oral solution, which comprises the following components in part by weight:
the preparation method of the calcium zinc gluconate oral solution comprises the following steps:
(1) adding purified water with the amount of 90% of the prescription amount into the batching tank, starting a stirring device and a steam valve, heating to 90 ℃, maintaining at 85 ℃, adding weighed calcium gluconate, and stirring for 15 minutes until the calcium gluconate is completely dissolved.
(2) And (2) maintaining the heating temperature at 90 ℃, adding zinc gluconate, lysine hydrochloride, sodium benzoate, sucralose and lactic acid into the material obtained in the step (1) in sequence, and stirring for 15 minutes until the materials are completely dissolved.
(3) The temperature of the liquid medicine is continuously heated to 100 ℃ and kept for 30 minutes, and then the steam valve is closed to stop heating.
(4) And (3) starting the condensed water, continuing stirring, cooling, stopping stirring until the temperature of the material is lower than 40 ℃, continuing adding purified water into the batching tank to full volume after adding the juicy peach essence, fixing the volume, and stirring for 15 minutes until the material is uniform.
(5) And filtering the prepared liquid medicine by a 0.45-micrometer titanium rod filter, transferring the liquid medicine into a liquid storage tank, and detecting the pH value of the liquid medicine, wherein the pH value is within a qualified range of 3.5-4.5, and the preferred pH value is 3.8-4.0. And after the oral liquid is detected to be qualified, filling the mixture by using an automatic forming filling and sealing machine for the oral liquid plastic bottle, wherein the selected packaging material is a plastic ampoule made of a polyester/low-density polyethylene oral liquid hard sheet (PET/PE). The loading amount is set to be 10.3ml, and the control range of the loading amount is 10.1 ml/piece to 10.3 ml/piece. And (4) qualified encapsulation standard: the seal is symmetrical, the blow molding protruding part is symmetrical, the plastic panel is flat and dense, and the filling amount is not less than 10.0 ml/piece. And finally, performing light inspection on the qualified filled sample, removing the leaked oral solution, and packaging.
Example 5
The embodiment provides a calcium zinc gluconate oral solution, which comprises the following components in part by weight:
the preparation method of the calcium zinc gluconate oral solution comprises the following steps:
(1) adding purified water with the amount of 90% of the prescription amount into the batching tank, starting a stirring device and a steam valve, heating to 85 ℃, maintaining at 85 ℃, adding weighed calcium gluconate, and stirring for 15 minutes until the calcium gluconate is completely dissolved.
(2) And (2) maintaining the heating temperature at 85 ℃, adding zinc gluconate, lysine hydrochloride, sodium benzoate, sucralose and lactic acid into the material obtained in the step (1) in sequence, and stirring for 15 minutes until the materials are completely dissolved.
(3) The temperature of the liquid medicine is continuously heated to 105 ℃ and kept for 30 minutes, and then the steam valve is closed to stop heating.
(4) And (3) starting the condensed water, continuing stirring, cooling, stopping stirring until the temperature of the material is lower than 40 ℃, continuing adding purified water into the batching tank to full volume after adding the juicy peach essence, fixing the volume, and stirring for 15 minutes until the material is uniform.
(5) And filtering the prepared liquid medicine by a 0.45-micrometer titanium rod filter, transferring the liquid medicine into a liquid storage tank, and detecting the pH value of the liquid medicine, wherein the pH value is within a qualified range of 3.5-4.5, and the preferred pH value is 3.8-4.0. And after the oral liquid is detected to be qualified, filling the mixture by using an automatic forming filling and sealing machine for the oral liquid plastic bottle, wherein the selected packaging material is a plastic ampoule made of a polyester/low-density polyethylene oral liquid hard sheet (PET/PE). The loading amount is set to be 10.3ml, and the control range of the loading amount is 10.1 ml/piece to 10.3 ml/piece. And (4) qualified encapsulation standard: the seal is symmetrical, the blow molding protruding part is symmetrical, the plastic panel is flat and dense, and the filling amount is not less than 10.0 ml/piece. And finally, performing light inspection on the qualified filled sample, removing the leaked oral solution, and packaging.
In order to verify the beneficial effects of the invention, the following quality evaluation and taste evaluation of the calcium zinc gluconate oral solution are specially carried out.
First, the calcium zinc gluconate oral solution prepared in examples 1 to 5 was subjected to influence factor tests (including high temperature tests, acceleration tests, freeze-thaw tests, and microbial limit tests) with a commercially available product 1 (manufacturer: aono (china) pharmaceutical co., ltd., lot No. 1906074), a commercially available product 2 (manufacturer: hubei noon pharmaceutical co., ltd., lot No. 19092076), and a commercially available product 3 (manufacturer: hubei fu man jinsheng pharmaceutical co., ltd., lot No. 191121).
High-temperature test: placing the sample and the commercial product under the condition of 60 ℃/45% RH, and respectively inspecting for 10 days, 20 days and 30 days; as shown in Table 1, it was found that the main drug contents of examples 1 to 5 and commercial products 1 to 3 were within the control limits (93% to 107%), and the 5-hydroxymethylfurfural and the glucuronic acid derivative were much less than the corresponding limits in the related substances, but the amino acid impurity contents of the aspartame-containing formulations (commercial product 1 and commercial product 3) in the commercial products were high, and under the condition of 60 ℃/45% RH, commercial product 1 was over-limited after standing for 20 days, commercial product 3 was over-limited after standing for 30 days, and three known amino acid impurities were not detected in examples 1 to 5 and commercial product 2 after standing for 30 days.
And (3) accelerated test: placing the sample and the commercial product under the condition of 40 ℃/75% RH, and respectively inspecting for 1 month, 3 months and 6 months; as shown in Table 2, it was found that the main drug contents of examples 1 to 5 and commercial products 1 to 3 were within the control limits (93% to 107%), and the 5-hydroxymethylfurfural and the glucuronic acid derivative were much smaller than the corresponding limits in the related substances, but the amino acid impurity contents of the formulations containing aspartame (commercial product 1 and commercial product 3) in the commercial products were high, and the amino acid impurity contents of commercial products 1 and 3 were both exceeded after leaving for one month under the condition of 40 ℃/75% RH, whereas the amino acid impurities of examples 1 to 5 and commercial product 2 were all not detected after leaving for 30 days.
Freeze-thaw test: respectively taking ten samples and commercial products, and performing low-temperature/high-temperature circulation for three times, wherein each circulation is that the samples are placed at the low temperature of minus 20 ℃ for 2 days and at the temperature of 40 ℃ for 2 days; as shown in table 3, the solution properties were not changed after the freeze-thaw cycles in examples 1 to 5, and it can be seen that the preparation process provided in the present invention can effectively inhibit the solid precipitation of calcium gluconate after repeated low/high temperature treatments.
And (3) microbial limit inspection: according to the microbiological limitation examination of non-sterile products 1105 in the fourth biological examination method of the China pharmacopoeia 2020 edition: microbial enumeration and 1106 "microbial Limit check of non-sterile products: control bacteria inspection method is carried out according to relevant regulations; as shown in tables 1 to 3, the microbial limit was acceptable in all of the different placement modes.
(II) evaluating mouthfeel: and randomly selecting 30 men and 30 women to score indexes such as sweet taste, sour taste, fragrance and the like of the calcium zinc gluconate oral solution prepared in the embodiment 1-5 and the commercial products 1-3, calculating a mean value, wherein the higher the score is, the higher the corresponding index degree is. The results are shown in table 4, as the dosage of sucralose increases, the sweet taste increases correspondingly, the sour taste decreases correspondingly, examples 2, 4 and 5 belong to formulas with higher relative comprehensive scores, and the indexes or the heat preservation temperature considered in the process have less influence on the mouthfeel.
TABLE 1 high temperature stability test results (60 ℃/45% RH)
Table 1 is continued:
table 1 is continued:
remarking: "/" indicates that the corresponding detection item is not detected.
TABLE 2 accelerated stability test results (40 ℃/75% RH)
Table 2 is continued:
table 2 is continued:
remarking: "/" indicates that the corresponding detection item is not detected.
TABLE 3 Freeze thaw test results
Remarking: "/" indicates that the corresponding detection item is not detected.
TABLE 4 taste evaluation results
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.
Claims (9)
2. the calcium zinc gluconate oral solution according to claim 1, wherein the pH is controlled within a range of 3.5 to 4.5.
3. The calcium zinc gluconate oral solution according to claim 2, wherein the pH is controlled within a range of 3.8 to 4.0.
4. The method of preparing an oral solution of calcium zinc gluconate as claimed in claim 1, comprising the steps of:
(1) adding 90% of purified water into a mixing tank, heating to a certain temperature, adding weighed calcium gluconate, and stirring until the calcium gluconate is dissolved;
(2) maintaining the heating temperature, sequentially adding zinc gluconate, lysine hydrochloride, sodium benzoate, sucralose and lactic acid into the material obtained in the step (1), and stirring until the materials are dissolved;
(3) heating to a certain temperature, keeping the temperature for 10-30 minutes, and stopping heating;
(4) and (4) cooling the material obtained in the step (3) to a temperature lower than 40 ℃, adding juicy peach essence, adding purified water to full volume, fixing the volume, uniformly stirring, filtering, and encapsulating.
5. The method for preparing calcium zinc gluconate oral solution according to claim 4, wherein the heating temperature in step (1) is 80-90 ℃.
6. The method for preparing calcium zinc gluconate oral solution according to claim 4, wherein the heating stabilization temperature in the step (2) is 80-90 ℃.
7. The method for preparing calcium zinc gluconate oral solution according to claim 4, wherein the incubation temperature in the step (3) is 100-110 ℃.
8. The method of claim 4, wherein the filtering step in the step (4) is performed by filtering the material through a 0.45 μm titanium rod filter.
9. The method for preparing calcium zinc gluconate oral solution according to claim 4, wherein in the step (4), the encapsulation packaging material used for encapsulation is a plastic ampoule made of polyester/low density polyethylene oral liquid pharmaceutical hard tablet.
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113069441A (en) * | 2021-03-29 | 2021-07-06 | 北京先通源医药科技股份有限公司 | Calcium zinc gluconate preparation and preparation method thereof |
CN113262202A (en) * | 2021-06-30 | 2021-08-17 | 江西益佰年药业股份有限公司 | Preparation process method of calcium zinc gluconate oral liquid |
CN113876699A (en) * | 2021-10-28 | 2022-01-04 | 昆明源瑞制药有限公司 | Compound zinc-iron-calcium oral solution and preparation method thereof |
CN115040477A (en) * | 2022-07-20 | 2022-09-13 | 北京鑫开元医药科技有限公司 | Calcium zinc gluconate oral solution and preparation method thereof |
CN115227717A (en) * | 2022-07-29 | 2022-10-25 | 国药控股星鲨制药(厦门)有限公司 | Pharmaceutical composition, application and preparation method of calcium zinc gluconate oral solution |
CN115844870A (en) * | 2022-11-30 | 2023-03-28 | 北京海晶生物医药科技有限公司 | Pharmaceutical composition containing zinc gluconate and preparation method thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20060062333A (en) * | 2004-12-03 | 2006-06-12 | 주식회사 메디넥스 | Zinc gluconate mixture which was good taste and masked to bitter taste of zinc gluconate |
CN103690521A (en) * | 2013-11-29 | 2014-04-02 | 湖北福人金身药业有限公司 | Calcium zinc gluconate oral solution |
CN109528644A (en) * | 2018-12-28 | 2019-03-29 | 重庆健能医药开发有限公司 | A kind of Zinc calcium gluconate oral solution and preparation method thereof |
-
2020
- 2020-10-26 CN CN202011153545.8A patent/CN112190575A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20060062333A (en) * | 2004-12-03 | 2006-06-12 | 주식회사 메디넥스 | Zinc gluconate mixture which was good taste and masked to bitter taste of zinc gluconate |
CN103690521A (en) * | 2013-11-29 | 2014-04-02 | 湖北福人金身药业有限公司 | Calcium zinc gluconate oral solution |
CN109528644A (en) * | 2018-12-28 | 2019-03-29 | 重庆健能医药开发有限公司 | A kind of Zinc calcium gluconate oral solution and preparation method thereof |
Non-Patent Citations (2)
Title |
---|
杨宗发等: "《药物制剂设备》", 30 April 2012, 人民军医出版社 * |
潘卫三等: "《工业药剂学》", 31 August 2015, 中国医药科技出版社 * |
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CN113262202A (en) * | 2021-06-30 | 2021-08-17 | 江西益佰年药业股份有限公司 | Preparation process method of calcium zinc gluconate oral liquid |
CN113876699A (en) * | 2021-10-28 | 2022-01-04 | 昆明源瑞制药有限公司 | Compound zinc-iron-calcium oral solution and preparation method thereof |
CN115040477A (en) * | 2022-07-20 | 2022-09-13 | 北京鑫开元医药科技有限公司 | Calcium zinc gluconate oral solution and preparation method thereof |
CN115040477B (en) * | 2022-07-20 | 2023-11-03 | 北京鑫开元医药科技有限公司 | Calcium zinc gluconate oral solution and preparation method thereof |
CN115227717A (en) * | 2022-07-29 | 2022-10-25 | 国药控股星鲨制药(厦门)有限公司 | Pharmaceutical composition, application and preparation method of calcium zinc gluconate oral solution |
CN115227717B (en) * | 2022-07-29 | 2024-02-09 | 国药控股星鲨制药(厦门)有限公司 | Pharmaceutical composition, application and preparation method of calcium zinc gluconate oral solution |
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