CN117883555A - Compound calcium gluconate oral solution and preparation method thereof - Google Patents
Compound calcium gluconate oral solution and preparation method thereof Download PDFInfo
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- CN117883555A CN117883555A CN202410302263.1A CN202410302263A CN117883555A CN 117883555 A CN117883555 A CN 117883555A CN 202410302263 A CN202410302263 A CN 202410302263A CN 117883555 A CN117883555 A CN 117883555A
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- calcium gluconate
- parts
- solution
- calcium
- compound
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- 229940042228 calcium gluconate oral solution Drugs 0.000 title claims abstract description 37
- 150000001875 compounds Chemical class 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 229960004494 calcium gluconate Drugs 0.000 claims abstract description 72
- 239000004227 calcium gluconate Substances 0.000 claims abstract description 72
- 235000013927 calcium gluconate Nutrition 0.000 claims abstract description 72
- 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 64
- 239000007788 liquid Substances 0.000 claims abstract description 36
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 claims abstract description 23
- 239000001527 calcium lactate Substances 0.000 claims abstract description 23
- 229960002401 calcium lactate Drugs 0.000 claims abstract description 23
- 235000011086 calcium lactate Nutrition 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 18
- 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 claims abstract description 17
- 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 claims abstract description 17
- 229930006000 Sucrose Natural products 0.000 claims abstract description 17
- 239000008103 glucose Substances 0.000 claims abstract description 17
- 239000005720 sucrose Substances 0.000 claims abstract description 17
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229960005069 calcium Drugs 0.000 claims abstract description 16
- 239000011575 calcium Substances 0.000 claims abstract description 16
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 63
- 239000000243 solution Substances 0.000 claims description 52
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 36
- 238000003756 stirring Methods 0.000 claims description 31
- 229920001690 polydopamine Polymers 0.000 claims description 29
- 239000008367 deionised water Substances 0.000 claims description 28
- 229910021641 deionized water Inorganic materials 0.000 claims description 28
- 239000002077 nanosphere Substances 0.000 claims description 27
- 235000003599 food sweetener Nutrition 0.000 claims description 26
- 239000003765 sweetening agent Substances 0.000 claims description 26
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 claims description 19
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 19
- 229960001149 dopamine hydrochloride Drugs 0.000 claims description 19
- 229910001868 water Inorganic materials 0.000 claims description 19
- 239000004310 lactic acid Substances 0.000 claims description 18
- 235000014655 lactic acid Nutrition 0.000 claims description 18
- 239000008213 purified water Substances 0.000 claims description 16
- 108010011619 6-Phytase Proteins 0.000 claims description 15
- 229940085127 phytase Drugs 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 14
- 239000002994 raw material Substances 0.000 claims description 13
- 238000009835 boiling Methods 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 238000000926 separation method Methods 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- KPQJOKRSYYJJEL-VLQRKCJKSA-K [Na+].[Na+].CC1(C)[C@H](CC[C@@]2(C)[C@H]1CC[C@]1(C)[C@@H]2C(=O)C=C2[C@@H]3C[C@](C)(CC[C@]3(C)CC[C@@]12C)C([O-])=O)O[C@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)C([O-])=O)C([O-])=O Chemical compound [Na+].[Na+].CC1(C)[C@H](CC[C@@]2(C)[C@H]1CC[C@]1(C)[C@@H]2C(=O)C=C2[C@@H]3C[C@](C)(CC[C@]3(C)CC[C@@]12C)C([O-])=O)O[C@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)C([O-])=O)C([O-])=O KPQJOKRSYYJJEL-VLQRKCJKSA-K 0.000 claims description 11
- -1 compound calcium gluconate Chemical class 0.000 claims description 9
- 229940106039 disodium glycyrrhizate Drugs 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 239000012141 concentrate Substances 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 7
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 6
- 238000011049 filling Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 238000007689 inspection Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000012982 microporous membrane Substances 0.000 claims description 4
- 238000004806 packaging method and process Methods 0.000 claims description 4
- 238000007789 sealing Methods 0.000 claims description 4
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- 239000004376 Sucralose Substances 0.000 claims description 3
- 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 description 3
- 235000019408 sucralose Nutrition 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- 229940109275 cyclamate Drugs 0.000 claims 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 abstract description 26
- 229910001424 calcium ion Inorganic materials 0.000 abstract description 26
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000010521 absorption reaction Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 8
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 7
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 7
- 229940068041 phytic acid Drugs 0.000 description 7
- 235000002949 phytic acid Nutrition 0.000 description 7
- 239000000467 phytic acid Substances 0.000 description 7
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 5
- 229940100688 oral solution Drugs 0.000 description 5
- 206010006956 Calcium deficiency Diseases 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 2
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 229960001462 sodium cyclamate Drugs 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229940069978 calcium supplement Drugs 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002366 mineral element Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- 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
- 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
- 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
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- 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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Obesity (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
The invention relates to the technical field of medicines, in particular to a formula of a compound calcium gluconate oral solution and a preparation method thereof. The invention adopts a compound formula of the calcium gluconate accelerator, the calcium gluconate, the calcium lactate, the sucrose and the glucose, thereby improving the stability of the oral liquid, improving the calcium content of the oral liquid and improving the utilization rate of calcium ions in the oral liquid by human bodies.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a formula of a compound calcium gluconate oral solution and a preparation method thereof.
Background
The calcium gluconate oral solution is a solution containing calcium gluconate (calcium gluconate) and is generally used for supplementing calcium elements required by human body. Such solutions play an important role in the medical, health and pharmaceutical treatment fields.
Calcium is one of the most abundant minerals in the human body and is critical to maintaining bone and tooth health and normal functions of nerves and muscles. The lack of calcium may cause health problems such as fracture initiation, osteoporosis, etc., and therefore, adequate calcium intake is critical to human health.
Calcium gluconate is an organic calcium salt with good bioavailability. Calcium gluconate is more readily absorbed by the human body than other forms of calcium supplements. Its form in oral solution makes it easier to enter the gastrointestinal tract, thereby improving the calcium absorption efficiency.
The compound calcium gluconate oral solution is a medicine which is prepared by taking high-bioavailability and safe calcium gluconate and calcium lactate as raw materials and taking purified water, sucrose, glucose, lactic acid and essence as auxiliary materials and is used for preventing and treating calcium deficiency. The compound calcium gluconate oral solution is a medicine which is prepared by taking high-bioavailability and safe calcium gluconate and calcium lactate as raw materials and taking purified water, sucrose, glucose, lactic acid and a sweetener as auxiliary materials and is used for preventing and treating calcium deficiency. The product is in the form of oral solution, has no disintegration and release processes of tablet, and can be rapidly absorbed and utilized by human body. However, because the saturated solubility of calcium gluconate is 3%, precipitation is easy to separate out, the product is unstable, the content of calcium ions is low, and the absorption and utilization rate of calcium ions in the product by human bodies is low. Therefore, how to improve the stability of the product, the solubility of calcium gluconate and the absorption of calcium ions by human body are all the problems to be solved by the person skilled in the art.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to solve the technical problems that: a compound calcium gluconate oral solution and its preparation method are provided.
A compound calcium gluconate oral solution is prepared from the following raw materials: calcium gluconate, calcium gluconate accelerator, calcium lactate, sucrose, glucose, lactic acid, sweetener, and purified water.
The sweetener is at least one of sucralose, sodium cyclamate and disodium glycyrrhizinate; preferably, the sweetener is disodium glycyrrhizate.
The main components of the product are as follows:
(1) Calcium gluconate:
chemical name: d-calcium gluconate salt monohydrate
The chemical structural formula:
，H2O
The molecular formula: c 12H22CaO14·H2 O
Molecular weight: 448.40
(2) Calcium lactate:
Chemical name: alpha-calcium hydroxy propionate pentahydrate
The chemical structural formula:
，5H2O
the molecular formula: c 6H10CaO6·5H2 O
Molecular weight: 308.30
Preferably, the compound calcium gluconate oral solution comprises the following raw materials in parts by mass:
4-6 parts of calcium gluconate, 3-6 parts of a calcium gluconate accelerator, 4-6 parts of calcium lactate, 9-11 parts of sucrose, 3-5 parts of glucose, 0.3-0.6 part of lactic acid and 0.01-0.015 part of a sweetener; 90-100 parts of purified water.
The sweetener is at least one of sucralose, sodium cyclamate and disodium glycyrrhizinate; preferably, the sweetener is disodium glycyrrhizate.
The preparation method of the calcium gluconate accelerant comprises the following steps:
(1) Dissolving diethanolamine in water to prepare diethanolamine solution with concentration of 0.8-1.2 mol/L; dissolving dopamine hydrochloride in water to prepare a dopamine hydrochloride solution with the concentration of 2.5-2.6 mol/L;
(2) Adding 22-23 parts by mass of the diethanolamine solution obtained in the step (1) into 10-15 parts by weight of 16-35wt% ethanol water solution, and stirring for 30-60min at 25-30 ℃ to obtain a solution A;
(3) Adding 5 parts of the dopamine hydrochloride solution obtained in the step (1) into the solution A obtained in the step (2), stirring for 24-48 hours at 25-30 ℃, separating out solid substances, and drying to obtain polydopamine nanospheres;
(4) Mixing 1-2 parts by mass of polydopamine nanospheres, 0.1-0.2 part by mass of phytase and 10-20 parts by mass of water, stirring for 30-60min at 25-30 ℃, separating out solid substances, and drying to obtain the calcium gluconate accelerator.
Preferably, the separation is a centrifugal separation with a centrifugal rotational speed of 8000-10000 rps.
The compound calcium gluconate oral solution is a medicine which is prepared by taking high-bioavailability and safe calcium gluconate and calcium lactate as raw materials and taking purified water, sucrose, glucose, lactic acid and a sweetener as auxiliary materials and is used for preventing and treating calcium deficiency. The product is in the form of oral solution, has no disintegration and release processes of tablet, and can be rapidly absorbed and utilized by human body. The saturated solubility of the calcium gluconate is 3%, precipitation is easy to separate out, the product is unstable, the content of calcium ions is low, and the absorption and utilization rate of the calcium ions in the product by human bodies is low.
According to the invention, the stability of the prepared compound calcium gluconate oral solution can be effectively improved by adding the calcium gluconate accelerator and the lactic acid, and the polydopamine nanospheres can be used for better adsorbing the calcium gluconate and the calcium lactate to form a stable dissolution system in a glucose and sucrose solution, and in addition, the polydopamine nanospheres can be used for adsorbing the calcium gluconate and the calcium lactate, and can be used for promoting the dissolution of the calcium gluconate and the calcium lactate and increasing the content of calcium ions in the oral solution. The polydopamine nanospheres can be adsorbed on the inner wall of the intestinal canal, so that the residence time of calcium gluconate and calcium lactate in the intestinal canal is prolonged. The phytase can degrade the phytic acid in plants, the phytic acid and calcium form indissoluble salts, and the interception effect of the phytic acid on the calcium gluconate can be reduced by using the phytase, so that the bioavailability of the calcium gluconate is improved. The combination of the two is more favorable for human body absorption.
The invention also provides a preparation method of the compound calcium gluconate oral solution, which comprises the following steps:
(1) Placing purified water into deionized equipment, heating and boiling the deionized water to 100 ℃ after the deionized water is removed, separating out 100ml of boiled deionized water, and preserving the heat for later use;
(2) Adding the deionized water with the dosage of 60-65% into a liquid preparation tank, weighing 40.00-60.00g of calcium gluconate, 40.00-60.00g of calcium lactate and 4.00-6.00g of lactic acid, continuously stirring, adding into the liquid preparation tank, continuously boiling for 30-60min, stopping heating, cooling to 50-55 ℃ to obtain active calcium liquid, and preserving heat for later use;
(3) Taking 90-100mL of boiled deionized water obtained in the step (1), adding 90.00-110.00g of sucrose and 30.00-50.00g of glucose, boiling and dissolving under stirring, adding 9.00-10.00g of activated carbon, standing for 20-40min, and filtering with a microporous membrane in a plate frame to obtain filtrate; mixing the filtrate with the active calcium solution obtained in the step (2), and uniformly stirring to obtain a compound calcium gluconate concentrate;
(4) Adding 0.10-0.15g of sweetener and 30.00-50.00g of calcium gluconate accelerant into the compound calcium gluconate concentrate obtained in the step (3), and uniformly stirring to obtain a liquid medicine; and finally, cooling the boiled deionized water obtained in the step (1) to 50-55 ℃, fixing the volume of the liquid medicine to 950mL by using the cooled boiled deionized water, then filling and sealing the liquid medicine, sterilizing for 10-30min at 100-110 ℃, performing light inspection, and packaging to obtain the compound calcium gluconate oral solution.
The invention has the beneficial effects that:
The invention adopts a compound formula of the calcium gluconate accelerator, the calcium gluconate, the calcium lactate, the sucrose and the glucose, thereby improving the stability of the oral liquid, improving the calcium content of the oral liquid and improving the utilization rate of calcium ions in the oral liquid by human bodies.
Detailed Description
In the present invention, all the equipment and raw materials are commercially available or commonly used in the industry, and the methods in the following examples are conventional in the art unless otherwise specified.
Example 1
A compound calcium gluconate oral solution consists of the following raw materials in parts by mass:
5 parts of calcium gluconate, 4 parts of calcium gluconate accelerator, 5 parts of calcium lactate, 10.2 parts of sucrose, 4 parts of glucose, 0.5 part of lactic acid and 0.012 part of sweetener; 95 parts of purified water.
A preparation method of a compound calcium gluconate oral solution comprises the following steps:
(1) Placing purified water into deionized equipment, heating and boiling the deionized water to 100 ℃ after the deionized water is removed, separating out 100ml of boiled deionized water, and preserving the heat for later use;
(2) Adding the deionized water with the dosage of 63% into a liquid preparation tank, weighing 50.00g g of calcium gluconate, 50.00g of calcium lactate and 5.00g of lactic acid, adding into the liquid preparation tank under continuous stirring, continuously boiling for 40min, stopping heating, cooling to 52 ℃ to obtain active calcium liquid, and preserving heat for later use;
(3) Taking 100mL of boiled deionized water obtained in the step (1), adding 102.00g of sucrose and 40.00g of glucose, boiling and dissolving under stirring, adding 10.00g of activated carbon, standing for 30min, and filtering with a plate and frame microporous membrane to obtain filtrate; mixing the filtrate with the active calcium solution obtained in the step (2), and uniformly stirring to obtain a compound calcium gluconate concentrate;
(4) Adding 0.12g of sweetener and 40g of calcium gluconate accelerant into the compound calcium gluconate concentrate obtained in the step (3), and uniformly stirring to obtain a liquid medicine; and (3) finally, cooling the boiled deionized water obtained in the step (1) to 51 ℃, fixing the volume of the liquid medicine to 950mL by using the cooled boiled deionized water, then filling and sealing the liquid medicine, sterilizing for 20min at 105 ℃, performing lamp inspection, and packaging to obtain the compound calcium gluconate oral solution.
The sweetener is disodium glycyrrhizate.
The preparation method of the calcium gluconate accelerant comprises the following steps:
(1) Dissolving diethanolamine in water to prepare diethanolamine solution with the concentration of 1 mol/L; dissolving dopamine hydrochloride in water to prepare a 2.6365 mol/L dopamine hydrochloride solution;
(2) Adding 22.4 parts by mass of the diethanolamine solution obtained in the step (1) into 12 parts by weight of 20wt% ethanol water solution, and stirring for 30min at 30 ℃ to obtain a solution A;
(3) Adding 5 parts of the dopamine hydrochloride solution obtained in the step (1) into the solution A obtained in the step (2), stirring for 24 hours at 30 ℃, separating out solid substances, and drying to obtain polydopamine nanospheres;
(4) According to the mass parts, 1 part of polydopamine nanospheres, 0.1 part of phytase and 10 parts of water are mixed, stirred for 30min at 30 ℃, solid matters are separated out, and the calcium gluconate accelerant is obtained after drying.
Preferably, the separation is a centrifugal separation at a rotational speed of 8000rps.
Example 2
The only difference from example 1 is that: lactic acid is not added to the formulation.
A compound calcium gluconate oral solution consists of the following raw materials in parts by mass:
5 parts of calcium gluconate, 4 parts of calcium gluconate accelerator, 5 parts of calcium lactate, 10.2 parts of sucrose, 4 parts of glucose and 0.012 part of sweetener; 95 parts of purified water.
The sweetener is disodium glycyrrhizate.
The preparation method of the calcium gluconate accelerant comprises the following steps:
(1) Dissolving diethanolamine in water to prepare diethanolamine solution with the concentration of 1 mol/L; dissolving dopamine hydrochloride in water to prepare a 2.6365 mol/L dopamine hydrochloride solution;
(2) Adding 22.4 parts by mass of the diethanolamine solution obtained in the step (1) into 12 parts by weight of 20wt% ethanol water solution, and stirring for 30min at 30 ℃ to obtain a solution A;
(3) Adding 5 parts of the dopamine hydrochloride solution obtained in the step (1) into the solution A obtained in the step (2), stirring for 24 hours at 30 ℃, separating out solid substances, and drying to obtain polydopamine nanospheres;
(4) According to the mass parts, 1 part of polydopamine nanospheres, 0.1 part of phytase and 10 parts of water are mixed, stirred for 30min at 30 ℃, solid matters are separated out, and the calcium gluconate accelerant is obtained after drying.
Preferably, the separation is a centrifugal separation at a rotational speed of 8000rps.
Example 3
The only difference from example 1 is that: no phytase is added to the calcium gluconate accelerator.
A compound calcium gluconate oral solution consists of the following raw materials in parts by mass:
5 parts of calcium gluconate, 4 parts of calcium gluconate accelerator, 5 parts of calcium lactate, 10.2 parts of sucrose, 4 parts of glucose, 0.5 part of lactic acid and 0.012 part of sweetener; 95 parts of purified water.
The sweetener is disodium glycyrrhizate.
The preparation method of the calcium gluconate accelerant comprises the following steps:
(1) Dissolving diethanolamine in water to prepare diethanolamine solution with the concentration of 1 mol/L; dissolving dopamine hydrochloride in water to prepare a 2.6365 mol/L dopamine hydrochloride solution;
(2) Adding 22.4 parts by mass of the diethanolamine solution obtained in the step (1) into 12 parts by weight of 20wt% ethanol water solution, and stirring for 30min at 30 ℃ to obtain a solution A;
(3) Adding 5 parts of the dopamine hydrochloride solution obtained in the step (1) into the solution A obtained in the step (2), stirring for 24 hours at 30 ℃, separating out solid substances, and drying to obtain polydopamine nanospheres;
(4) Mixing 1 part of polydopamine nanospheres and 10 parts of water according to parts by mass, stirring for 30min at 30 ℃, separating out solid substances, and drying to obtain the calcium gluconate accelerator.
Preferably, the separation is a centrifugal separation at a rotational speed of 8000rps.
Example 4
The only difference from example 1 is that: the calcium gluconate promoter is phytase.
A compound calcium gluconate oral solution consists of the following raw materials in parts by mass:
5 parts of calcium gluconate, 0.4 part of calcium gluconate accelerator, 5 parts of calcium lactate, 10.2 parts of sucrose, 4 parts of glucose, 0.5 part of lactic acid and 0.012 part of sweetener; 95 parts of purified water.
The sweetener is disodium glycyrrhizate.
Comparative example 1
The only difference from example 1 is that: no calcium gluconate accelerator is added
A compound calcium gluconate oral solution consists of the following raw materials in parts by mass:
5 parts of calcium gluconate, 5 parts of calcium lactate, 10.2 parts of sucrose, 4 parts of glucose, 0.5 part of lactic acid and 0.012 part of sweetener; 95 parts of purified water.
The sweetener is disodium glycyrrhizate.
Comparative example 2
A compound calcium gluconate oral solution consists of the following raw materials in parts by mass:
5 parts of calcium gluconate, 4 parts of calcium gluconate accelerator, 5 parts of calcium lactate, 0.5 part of lactic acid and 0.012 part of sweetener; 95 parts of purified water.
A preparation method of a compound calcium gluconate oral solution comprises the following steps:
(1) Placing purified water into deionized equipment, heating and boiling the deionized water to 100 ℃ after the deionized water is removed, separating out 100ml of boiled deionized water, and preserving the heat for later use;
(2) Adding the deionized water with the dosage of 63% into a liquid preparation tank, weighing 50.00g g of calcium gluconate, 50.00g of calcium lactate and 5.00g of lactic acid, adding into the liquid preparation tank under continuous stirring, continuously boiling for 40min, stopping heating, cooling to 52 ℃ to obtain active calcium liquid, and preserving heat for later use;
(3) Taking 100mL of boiled deionized water obtained in the step (1), boiling and dissolving under stirring, adding 10.00g of activated carbon, standing for 30min, and filtering with a microporous membrane in a plate frame to obtain a filtrate; mixing the filtrate with the active calcium solution obtained in the step (2), and uniformly stirring to obtain a compound calcium gluconate concentrate;
(4) Adding 0.12g of sweetener and 40g of calcium gluconate accelerant into the compound calcium gluconate concentrate obtained in the step (3), and uniformly stirring to obtain a liquid medicine; and (3) finally, cooling the boiled deionized water obtained in the step (1) to 51 ℃, fixing the volume of the liquid medicine to 950mL by using the cooled boiled deionized water, then filling and sealing the liquid medicine, sterilizing for 20min at 105 ℃, performing lamp inspection, and packaging to obtain the compound calcium gluconate oral solution.
The sweetener is disodium glycyrrhizate.
The preparation method of the calcium gluconate accelerant comprises the following steps:
(1) Dissolving diethanolamine in water to prepare diethanolamine solution with the concentration of 1 mol/L; dissolving dopamine hydrochloride in water to prepare a 2.6365 mol/L dopamine hydrochloride solution;
(2) Adding 22.4 parts by mass of the diethanolamine solution obtained in the step (1) into 12 parts by weight of 20wt% ethanol water solution, and stirring for 30min at 30 ℃ to obtain a solution A;
(3) Adding 5 parts of the dopamine hydrochloride solution obtained in the step (1) into the solution A obtained in the step (2), stirring for 24 hours at 30 ℃, separating out solid substances, and drying to obtain polydopamine nanospheres;
(4) According to the mass parts, 1 part of polydopamine nanospheres, 0.1 part of phytase and 10 parts of water are mixed, stirred for 30min at 30 ℃, solid matters are separated out, and the calcium gluconate accelerant is obtained after drying.
Preferably, the separation is a centrifugal separation at a rotational speed of 8000rps.
Test example 1:
stability investigation: standing at 5 deg.C for 30 days, and standing at 25 deg.C for 30 days.
Table 1: stability investigation results
Test example 2
The compound calcium gluconate oral solution prepared in example 1, example 3 and comparative example 1 is filtered by adopting a microporous filter membrane which is independently packaged in a sterile mode and is RMF50M2PS of Jiangsu green Engineer scientific instruments Co., ltd, the pore diameter of the filter membrane is 0.22 mu M, and the compound calcium gluconate oral solution is prepared completely new. And (3) detecting calcium ions of the filtered compound calcium gluconate oral solution.
Table 2: calcium ion detection results
As can be seen from tables 1 and 2, the stability of the prepared compound calcium gluconate oral solution can be effectively improved by adding the calcium gluconate accelerator and the lactic acid.
Firstly, the polydopamine nanospheres are adopted to adsorb calcium ions in the compound calcium gluconate oral solution, and as the surfaces of the polydopamine nanospheres are provided with a large number of hydroxyl groups, amino groups and other active groups, the polydopamine nanospheres have strong adsorptivity to the calcium ions, can aggregate the calcium ions in the oral solution, so that more calcium ions can be dissolved in the solution, the aim of improving the concentration of the calcium ions in the calcium gluconate oral solution is fulfilled, and in addition, the polydopamine has good biocompatibility, is harmless to human bodies, can be adhered to intestinal tracts, and can also play a role in slow release and promote the absorption of the calcium ions by human bodies. Because of the existence of the polydopamine nanospheres, the content of calcium ions in the residual oral liquid after the polydopamine nanospheres are filtered out is far less than the saturated solubility of the polydopamine nanospheres, so that the stability of the polydopamine nanospheres is further improved.
In order to further promote the absorption of calcium ions in the oral liquid by a human body, phytase is added in the oral liquid to weaken the influence of phytic acid on the absorption of the calcium ions. The most remarkable features of phytic acid are its extremely strong complexation with metal ions and oxidation resistance. This unique property makes it of wide use. In developed countries, phytic acid has been used in many industries such as food, medicine, chemical industry, etc. Its use as a nutritional value increasing mineral elements has been common. According to the invention, the polydopamine is considered to absorb more calcium ions, and can slowly release the calcium ions, and the phytase belongs to one of proteins, and can be well absorbed on polydopamine nanospheres and is afraid of being unstable in aqueous solution, so that the polydopamine nanospheres are treated by the phytase firstly, the phytase is adsorbed on the polydopamine nanospheres, and then the treated polydopamine nanospheres are used for adsorbing the calcium ions in the oral liquid, so that the phytase further protects the calcium ions, and the influence of the phytic acid on the absorption of the calcium ions is weakened. The two components act together to better promote the absorption of calcium ions in the oral liquid by human body.
Therefore, the polydopamine nanospheres treated by the phytase are used as the accelerator, so that the solubility of calcium gluconate is improved, the stability of the oral liquid is maintained, and the absorption of calcium ions by a human body is improved.
Claims (6)
1. The compound calcium gluconate oral solution is characterized by comprising the following raw materials in parts by mass: 4-6 parts of calcium gluconate, 3-6 parts of a calcium gluconate accelerator, 4-6 parts of calcium lactate, 9-11 parts of sucrose, 3-5 parts of glucose, 0.3-0.6 part of lactic acid and 0.01-0.015 part of a sweetener; 90-100 parts of purified water;
The preparation method of the calcium gluconate accelerant comprises the following steps:
(1) Dissolving diethanolamine in water to prepare diethanolamine solution; dissolving dopamine hydrochloride in water to prepare a dopamine hydrochloride solution;
(2) Adding 22-23 parts by mass of the diethanolamine solution obtained in the step (1) into 10-15 parts by mass of ethanol water solution, and stirring for 30-60min at 25-30 ℃ to obtain solution A;
(3) Adding 5 parts of the dopamine hydrochloride solution obtained in the step (1) into the solution A obtained in the step (2), stirring for 24-48 hours at 25-30 ℃, separating out solid substances, and drying to obtain polydopamine nanospheres;
(4) Mixing 1-2 parts by mass of polydopamine nanospheres, 0.1-0.2 part by mass of phytase and 10-20 parts by mass of water, stirring for 30-60min at 25-30 ℃, separating out solid substances, and drying to obtain the calcium gluconate accelerator.
2. The compound calcium gluconate oral solution of claim 1, wherein the sweetener is at least one of sucralose, cyclamate, and disodium glycyrrhizate.
3. The compound calcium gluconate oral solution of claim 1, wherein the concentration of the diethanolamine solution is 0.8-1.2mol/L, and the concentration of the dopamine hydrochloride solution is 2.5-2.6 mol/L.
4. The compound calcium gluconate oral solution according to claim 1, wherein the mass percentage of the ethanol aqueous solution is 16-35wt%.
5. The compound calcium gluconate oral solution of claim 1, wherein the separation is centrifugal separation, and the centrifugal rotation speed is 8000-10000 rps.
6. The method for preparing the compound calcium gluconate oral solution according to any one of claims 1 to 5, comprising the following steps:
(1) Placing purified water into deionized equipment, heating and boiling the deionized water to 100 ℃ after the deionized water is removed, separating out 100ml of boiled deionized water, and preserving the heat for later use;
(2) Adding the deionized water with the dosage of 60-65% into a liquid preparation tank, weighing 40.00-60.00g of calcium gluconate, 40.00-60.00g of calcium lactate and 4.00-6.00g of lactic acid, continuously stirring, adding into the liquid preparation tank, continuously boiling for 30-60min, stopping heating, cooling to 50-55 ℃ to obtain active calcium liquid, and preserving heat for later use;
(3) Taking 90-100mL of boiled deionized water obtained in the step (1), adding 90.00-110.00g of sucrose and 30.00-50.00g of glucose, boiling and dissolving under stirring, adding 9.00-10.00g of activated carbon, standing for 20-40min, and filtering with a microporous membrane in a plate frame to obtain filtrate; mixing the filtrate with the active calcium solution obtained in the step (2), and uniformly stirring to obtain a compound calcium gluconate concentrate;
(4) Adding 0.10-0.15g of sweetener and 30.00-50.00g of calcium gluconate accelerant into the compound calcium gluconate concentrate obtained in the step (3), and uniformly stirring to obtain a liquid medicine; and finally, cooling the boiled deionized water obtained in the step (1) to 50-55 ℃, fixing the volume of the liquid medicine to 950mL by using the cooled boiled deionized water, then filling and sealing the liquid medicine, sterilizing for 10-30min at 100-110 ℃, performing light inspection, and packaging to obtain the compound calcium gluconate oral solution.
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