CN116983309A - Insoluble antiallergic medicinal preparation and preparation method thereof - Google Patents
Insoluble antiallergic medicinal preparation and preparation method thereof Download PDFInfo
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- CN116983309A CN116983309A CN202210438142.0A CN202210438142A CN116983309A CN 116983309 A CN116983309 A CN 116983309A CN 202210438142 A CN202210438142 A CN 202210438142A CN 116983309 A CN116983309 A CN 116983309A
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- purified water
- sucrose
- rupatadine fumarate
- hydrogen phosphate
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- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 230000003266 anti-allergic effect Effects 0.000 title claims abstract description 15
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 72
- 239000007788 liquid Substances 0.000 claims abstract description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 53
- JYBLCDXVHQWMSU-WLHGVMLRSA-N (e)-but-2-enedioic acid;8-chloro-11-[1-[(5-methylpyridin-3-yl)methyl]piperidin-4-ylidene]-5,6-dihydrobenzo[1,2]cyclohepta[2,4-b]pyridine Chemical compound OC(=O)\C=C\C(O)=O.CC1=CN=CC(CN2CCC(CC2)=C2C3=NC=CC=C3CCC3=CC(Cl)=CC=C32)=C1 JYBLCDXVHQWMSU-WLHGVMLRSA-N 0.000 claims abstract description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000008213 purified water Substances 0.000 claims abstract description 29
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims abstract description 25
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims abstract description 25
- 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 25
- 229930006000 Sucrose Natural products 0.000 claims abstract description 25
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims abstract description 25
- 239000000796 flavoring agent Substances 0.000 claims abstract description 25
- IZMJMCDDWKSTTK-UHFFFAOYSA-N quinoline yellow Chemical compound C1=CC=CC2=NC(C3C(C4=CC=CC=C4C3=O)=O)=CC=C21 IZMJMCDDWKSTTK-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229940051201 quinoline yellow Drugs 0.000 claims abstract description 25
- 235000012752 quinoline yellow Nutrition 0.000 claims abstract description 25
- 239000004172 quinoline yellow Substances 0.000 claims abstract description 25
- 229940085605 saccharin sodium Drugs 0.000 claims abstract description 25
- 239000005720 sucrose Substances 0.000 claims abstract description 25
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 24
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 20
- 238000004090 dissolution Methods 0.000 claims abstract description 20
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 20
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 12
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 10
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 10
- 239000011718 vitamin C Substances 0.000 claims abstract description 10
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims abstract description 8
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims abstract description 8
- 229960002216 methylparaben Drugs 0.000 claims abstract description 8
- 150000007524 organic acids Chemical class 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 61
- 239000003814 drug Substances 0.000 claims description 45
- 241000234295 Musa Species 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 18
- 229960004106 citric acid Drugs 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 13
- 235000019634 flavors Nutrition 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 7
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 2
- 229960004889 salicylic acid Drugs 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 240000005561 Musa balbisiana Species 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 18
- 229940095102 methyl benzoate Drugs 0.000 description 9
- 229920000728 polyester Polymers 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 229960004543 anhydrous citric acid Drugs 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 229960004756 ethanol Drugs 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 229960005328 rupatadine Drugs 0.000 description 4
- WUZYKBABMWJHDL-UHFFFAOYSA-N rupatadine Chemical compound CC1=CN=CC(CN2CCC(CC2)=C2C3=NC=CC=C3CCC3=CC(Cl)=CC=C32)=C1 WUZYKBABMWJHDL-UHFFFAOYSA-N 0.000 description 4
- 239000006184 cosolvent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 108010003541 Platelet Activating Factor Proteins 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010052568 Urticaria chronic Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000024376 chronic urticaria Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application discloses a poorly soluble antiallergic pharmaceutical preparation and a preparation method thereof. The anti-allergic medicinal preparation provided by the application comprises the following raw materials in parts by mass: 0.1-0.3 part of rupatadine fumarate, 10-25 parts of propylene glycol, 5-10 parts of polyethylene glycol, 3-10 parts of ethanol, 0.05-0.15 part of methyl paraben, 0.4-0.6 part of organic acid or salt thereof, 0.05-0.15 part of vitamin C, 0.5-0.9 part of anhydrous disodium hydrogen phosphate, 0.02-0.08 part of saccharin sodium, 25-40 parts of sucrose, 0.00005-0.00015 part of quinoline yellow, 0.2-0.3 part of banana flavoring agent and the balance of purified water. According to the preparation method, the rupatadine fumarate oral liquid is subjected to sample preparation according to the prescription and the process, the dissolution of the indissoluble raw material rupatadine fumarate in the preparation process is solved, the operability is high, and the sample quality is stable.
Description
Technical Field
The application belongs to the field of medicines, and particularly relates to a poorly soluble antiallergic medicinal preparation and a preparation method thereof.
Background
Rupatadine fumarate has dual actions of antihistamine and antagonizing Platelet Activating Factor (PAF). Because rupatadine has the capability of blocking release, according to the suggestion of clinical guidelines, the rupatadine can be considered to effectively relieve chronic urticaria for histamine and other inflammatory mediators, thereby relieving the symptoms of other forms of urticaria. The product is a pale yellow clear liquid preparation for oral administration, which is prepared by dissolving the raw material medicines in a proper solvent.
In the pediatric population, rupatadine is rapidly absorbed in a subset of children between 2 and 5 years and between 6 and 11 years, with mean Cmax values of 1.9 and 2.5ng/ml, respectively, after repeated oral administration. For exposure, the average total area under the curve (AUC) for children aged 2-5 is 10.4ng t/ml and for children aged 6-11 is 10.7ng t/ml. Rupatadine has an average half-life of 15.9 hours in children between 2 and 5 years of age and 12.3 hours in children between 6 and 11 years of age.
The rupatadine fumarate oral solution has longer dissolution time, larger production energy consumption, unstable storage process and easy impurity generation to influence the medication safety in the preparation process.
Disclosure of Invention
The application aims to provide a poorly soluble antiallergic medicinal preparation and a preparation method thereof.
The anti-allergic medicinal preparation provided by the application comprises the following raw materials in parts by mass: 0.1-0.3 part of rupatadine fumarate, 10-25 parts of propylene glycol, 5-10 parts of polyethylene glycol, 3-10 parts of ethanol, 0.05-0.15 part of methyl paraben, 0.4-0.6 part of organic acid or salt thereof, 0-0.15 part of vitamin C, 0.5-0.9 part of anhydrous disodium hydrogen phosphate, 0.02-0.08 part of saccharin sodium, 25-40 parts of sucrose, 0.00005-0.00015 part of quinoline yellow, 0.2-0.3 part of banana flavoring agent and the balance of purified water.
The organic acids include, but are not limited to, citric acid, ascorbic acid, salicylic acid, and the like.
The antiallergic preparation is prepared by the method comprising the following steps of;
1) Dissolving propylene glycol, polyethylene glycol, ethanol, organic acid or its salt, vitamin C and rupatadine fumarate in purified water with a prescription amount of 50% at 60deg.C, and naming the obtained solution as medicinal liquid (1) after dissolving completely;
2) Taking purified water with the prescription amount of 50%, dissolving sucrose, disodium hydrogen phosphate and saccharin sodium at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) and the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
The method can further comprise the step of filling the prepared liquid medicine into clean oral solid medicinal polyester bottles by a filling machine, wherein each bottle is 120ml.
The application uses organic acid or salt thereof to increase the solubility of rupatadine fumarate, the application uses a mixed solvent to assist dissolution, and adds organic solvent with specific composition and proportion into water to become the mixed solvent, further increases the solubility of rupatadine fumarate, and adds trace vitamin C to enhance the stability of rupatadine fumarate oral liquid.
According to the preparation method, the rupatadine fumarate oral liquid is subjected to sample preparation according to the prescription and the process, the dissolution of the indissoluble raw material rupatadine fumarate in the preparation process is solved, the operability is high, and the sample quality is stable.
Detailed Description
The following detailed description of the application is provided in connection with the accompanying drawings that are presented to illustrate the application and not to limit the scope thereof. The examples provided below are intended as guidelines for further modifications by one of ordinary skill in the art and are not to be construed as limiting the application in any way.
The experimental methods in the following examples, unless otherwise specified, are conventional methods, and are carried out according to techniques or conditions described in the literature in the field or according to the product specifications. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Comparative example 1,
The weight of each raw and auxiliary material used for preparing 10 bottles of 120ml rupatadine fumarate oral liquid is 1.536g, 1.2g of methyl paraben, 5.586g of citric acid, 8.772g of anhydrous disodium hydrogen phosphate, 0.6g of saccharin sodium, 360g of sucrose, 0.0012g of quinoline yellow, 3g of banana flavoring agent and the balance of purified water.
The preparation process comprises the following steps:
1) Dissolving citric acid, rupatadine fumarate and methyl hydroxybenzoate in purified water with a prescription amount of 50% at 60 ℃, and obtaining a liquid medicine (1) after dissolving completely;
2) Taking purified water with the prescription amount of 50%, dissolving sucrose, disodium hydrogen phosphate and saccharin sodium at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) with the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
4) Measuring the pH value and the quality of the solution before and after constant volume;
5) The prepared liquid medicine is split-packed into clean oral solid medicinal polyester bottles by a filling machine, and each bottle is 120ml.
Comparative example 2,
The weight of each raw and auxiliary material used for preparing 10 bottles of 120ml rupatadine fumarate oral liquid is 1.536g, propylene glycol 240g, methyl benzoate 1.2g, citric acid 5.586g, anhydrous disodium hydrogen phosphate 8.772g, saccharin sodium 0.6g, sucrose 360g, quinoline yellow 0.0012g, banana flavoring agent 3g and the rest of purified water.
The preparation process comprises the following steps:
1) Dissolving propylene glycol, anhydrous citric acid, rupatadine fumarate and methyl benzoate in 50% of purified water at 60deg.C, and collecting the solution (1);
2) Dissolving sucrose, disodium hydrogen phosphate and saccharin sodium in purified water with the prescription amount of 50% at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) with the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
4) And measuring the pH value and the quality of the solution before and after the constant volume.
5) And filling the prepared liquid medicine into clean oral solid medicinal polyester bottles by a filling machine, wherein each bottle is 120ml.
Comparative example 3,
The preparation process comprises the following steps: the weight of each raw and auxiliary material used for preparing 10 bottles of 120ml rupatadine fumarate oral liquid is 1.536g, propylene glycol 160g, polyethylene glycol 80g, methyl benzoate 1.2g, citric acid 5.586g, anhydrous disodium hydrogen phosphate 8.772g, saccharin sodium 0.6g, sucrose 360g, quinoline yellow 0.0012g and banana flavoring agent 3g.
1) Dissolving propylene glycol, polyethylene glycol, citric acid, rupatadine fumarate and methyl hydroxybenzoate in purified water with a prescription amount of 50% at 60 ℃, and naming the mixture as a liquid medicine (1) after dissolving completely;
2) Dissolving sucrose, disodium hydrogen phosphate and saccharin sodium in purified water with the prescription amount of 50% at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) with the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
4) And measuring the pH value and the quality of the solution before and after the constant volume.
5) And filling the prepared liquid medicine into clean oral solid medicinal polyester bottles by a filling machine, wherein each bottle is 120ml.
Comparative example 4, formulation and dosage
The weight of each raw and auxiliary material used for preparing 10 bottles of 120ml rupatadine fumarate oral liquid is 1.536g, propylene glycol is 200g, ethanol is 40g, methyl benzoate is 1.2g, citric acid is 5.586g, anhydrous disodium hydrogen phosphate is 8.772g, saccharin sodium is 0.6g, sucrose is 360g, quinoline yellow is 0.0012g, and banana flavoring agent is 3g.
1) Dissolving propylene glycol, citric acid, ethanol, rupatadine fumarate and methyl benzoate in purified water with a prescription amount of 50% at 60 ℃, and naming the mixture as a liquid medicine (1) after the dissolution is completed;
2) Taking purified water with the prescription amount of 50%, dissolving sucrose, disodium hydrogen phosphate and saccharin sodium at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) with the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
4) And (5) measuring the pH value and the quality of the solution before and after the constant volume.
5) The prepared liquid medicine is split-packed into clean oral solid medicinal polyester bottles by a filling machine, and each bottle is 120ml.
Example 1, prescription composition and dosage
The weight of each raw and auxiliary material used for preparing 10 bottles of 120ml rupatadine fumarate oral liquid is 1.536g, propylene glycol is 120g, polyethylene glycol is 80g, ethanol is 40g, methyl benzoate is 1.2g, anhydrous citric acid is 5.586g, anhydrous disodium hydrogen phosphate is 8.772g, saccharin sodium is 0.6g, sucrose is 360g, quinoline yellow is 0.0012g and banana flavoring agent is 3g.
1) Dissolving propylene glycol, polyethylene glycol, ethanol, citric acid, rupatadine fumarate and methyl hydroxybenzoate in purified water with a prescription amount of 50% at 60deg.C, and naming the obtained solution as medicinal liquid (1);
2) Dissolving sucrose, disodium hydrogen phosphate and saccharin sodium in purified water with the prescription amount of 50% at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) with the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
4) And measuring the pH value and the quality of the solution before and after the constant volume.
5) And filling the prepared liquid medicine into clean oral solid medicinal polyester bottles by a filling machine, wherein each bottle is 120ml.
Example 2 prescription composition and dosage
The weight of each raw and auxiliary material used for preparing 10 bottles of 120ml rupatadine fumarate oral liquid is 1.536g, propylene glycol is 100g, polyethylene glycol is 90g, ethanol is 50g, methyl benzoate is 1.2g, anhydrous citric acid is 5.586g, anhydrous disodium hydrogen phosphate is 8.772g, saccharin sodium is 0.6g, sucrose is 360g, quinoline yellow is 0.0012g and banana flavoring agent is 3g.
1) Dissolving propylene glycol, polyethylene glycol, ethanol, citric acid, rupatadine fumarate and methyl hydroxybenzoate in purified water with a prescription amount of 50% at 60deg.C, and naming the obtained solution as medicinal liquid (1);
2) Dissolving sucrose, disodium hydrogen phosphate and saccharin sodium in purified water with the prescription amount of 50% at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) with the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
4) And measuring the pH value and the quality of the solution before and after the constant volume.
5) And filling the prepared liquid medicine into clean oral solid medicinal polyester bottles by a filling machine, wherein each bottle is 120ml.
Example 3 prescription composition and dosage
The weight of each raw and auxiliary material used for preparing 10 bottles of 120ml rupatadine fumarate oral liquid is 1.536g, propylene glycol 140g, polyethylene glycol 70g, ethanol 30g, methyl benzoate 1.2g, anhydrous citric acid 5.586g, anhydrous disodium hydrogen phosphate 8.772g, saccharin sodium 0.6g, sucrose 360g, quinoline yellow 0.0012g and banana flavoring agent 3g.
1) Dissolving propylene glycol, polyethylene glycol, ethanol, citric acid, rupatadine fumarate and methyl hydroxybenzoate in purified water with a prescription amount of 50% at 60deg.C, and naming the obtained solution as medicinal liquid (1);
2) Dissolving sucrose, disodium hydrogen phosphate and saccharin sodium in purified water with the prescription amount of 50% at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) with the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
4) And measuring the pH value and the quality of the solution before and after the constant volume.
5) And filling the prepared liquid medicine into clean oral solid medicinal polyester bottles by a filling machine, wherein each bottle is 120ml.
Example 4 prescription composition and dosage
The weight of each raw and auxiliary material used for preparing 10 bottles of 120ml rupatadine fumarate oral liquid is 1.536g, propylene glycol is 120g, polyethylene glycol is 80g, ethanol is 40g, vitamin C is 1g, methyl benzoate is 1.2g, anhydrous citric acid is 5.586g, anhydrous disodium hydrogen phosphate is 8.772g, saccharin sodium is 0.6g, sucrose is 360g, quinoline yellow is 0.0012g, and banana flavoring agent is 3g.
1) Dissolving propylene glycol, polyethylene glycol, ethanol, vitamin C, citric acid, rupatadine fumarate and methyl hydroxybenzoate in purified water with a prescription amount of 50% at 60deg.C, and naming the obtained solution as medicinal liquid (1);
2) Dissolving sucrose, disodium hydrogen phosphate and saccharin sodium in purified water with the prescription amount of 50% at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) with the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
4) And measuring the pH value and the quality of the solution before and after the constant volume.
5) And filling the prepared liquid medicine into clean oral solid medicinal polyester bottles by a filling machine, wherein each bottle is 120ml.
The above examples were subjected to the following tests for dissolution rate, content and related substances:
the above comparative examples 1 to 4 and examples 1 and 4 were subjected to the influence factor test, and the samples were subjected to the content and related substances comparison for 30 days and 0 day under the conditions of high temperature of 60 ℃, high temperature of 40 ℃ and illumination of 5000Lx, and the following tables:
the results show that the dissolution rate of the raw materials in water and difficultly dissolved, after the organic salt and the mixed solvent are added, can be increased, under the condition of 60 ℃, the dissolution rate of the raw materials is slower without adding the cosolvent, the dissolution rate is improved after adding the cosolvent, especially when the mixed solvent consisting of propylene glycol, polyethylene glycol and ethanol is added, the dissolution rate is obviously improved, and under the condition of influencing factors, the content of the sample added with the cosolvent and related substances are in a qualified range, the sample is stable, and the storage stability is further improved by adding trace vitamin C.
The present application is described in detail above. It will be apparent to those skilled in the art that the present application can be practiced in a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the application and without undue experimentation. While the application has been described with respect to specific embodiments, it will be appreciated that the application may be further modified. In general, this application is intended to cover any variations, uses, or adaptations of the application following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice within the art to which the application pertains.
Claims (7)
1. The insoluble antiallergic medicinal preparation comprises the following raw materials in parts by mass: 0.1-0.3 part of rupatadine fumarate, 10-25 parts of propylene glycol, 5-10 parts of polyethylene glycol, 3-10 parts of ethanol, 0.05-0.15 part of methyl paraben, 0.4-0.6 part of organic acid or salt thereof, 0.5-0.9 part of anhydrous disodium hydrogen phosphate, 0.02-0.08 part of saccharin sodium, 0-0.15 part of vitamin C, 25-40 parts of sucrose, 0.00005-0.00015 part of quinoline yellow, 0.2-0.3 part of banana flavoring agent and the balance of purified water.
2. The antiallergic pharmaceutical formulation of claim 1, wherein: the organic acid is at least one of citric acid, ascorbic acid and salicylic acid.
3. The poorly soluble antiallergic pharmaceutical formulation of claim 2, wherein: the raw materials and the auxiliary materials comprise the following substances in parts by mass: 1.536 parts of rupatadine fumarate, 120 parts of propylene glycol, 80 parts of polyethylene glycol, 40 parts of ethanol, 1.2 parts of methylparaben, 5.586 parts of citric acid, 8.772 parts of anhydrous disodium hydrogen phosphate, 0.6 part of saccharin sodium, 360 parts of sucrose, 0.0012 parts of quinoline yellow, 3 parts of banana flavoring agent and the balance of purified water.
4. The poorly soluble antiallergic pharmaceutical formulation of claim 2, wherein: the raw materials and the auxiliary materials comprise the following substances in parts by mass: 1.536 parts of rupatadine fumarate, 100 parts of propylene glycol, 90 parts of polyethylene glycol, 50 parts of ethanol, 1.2 parts of methylparaben, 5.586 parts of citric acid, 8.772 parts of anhydrous disodium hydrogen phosphate, 0.6 part of saccharin sodium, 360 parts of sucrose, 0.0012 parts of quinoline yellow, 3 parts of banana flavoring agent and the balance of purified water.
5. The poorly soluble antiallergic pharmaceutical formulation of claim 2, wherein: the raw materials and the auxiliary materials comprise the following substances in parts by mass: 1.536 parts of rupatadine fumarate, 140 parts of propylene glycol, 70 parts of polyethylene glycol, 30 parts of ethanol, 1.2 parts of methylparaben, 5.586 parts of citric acid, 8.772 parts of anhydrous disodium hydrogen phosphate, 0.6 part of saccharin sodium, 360 parts of sucrose, 0.0012 parts of quinoline yellow, 3 parts of banana flavoring agent and the balance of purified water.
6. The poorly soluble antiallergic pharmaceutical formulation of claim 2, wherein: the raw materials and the auxiliary materials comprise the following substances in parts by mass: 1.536 parts of rupatadine fumarate, 120 parts of propylene glycol, 80 parts of polyethylene glycol, 40 parts of ethanol, 1 part of vitamin C, 1.2 parts of methylparaben, 5.586 parts of citric acid, 8.772 parts of anhydrous disodium hydrogen phosphate, 0.6 part of saccharin sodium, 360 parts of sucrose, 0.0012 part of quinoline yellow, 3 parts of banana flavoring agent and the balance of purified water.
7. A method of preparing an antiallergic pharmaceutical formulation of any one of claims 1-6, comprising the steps of:
1) Dissolving propylene glycol, polyethylene glycol, ethanol, organic acid or its salt, vitamin C and rupatadine fumarate in purified water with a prescription amount of 50% at 60deg.C, and naming the obtained solution as medicinal liquid (1) after dissolving completely;
2) Taking purified water with the prescription amount of 50%, dissolving sucrose, disodium hydrogen phosphate and saccharin sodium at 60 ℃, and naming the mixture as a liquid medicine (2) after complete dissolution;
3) Mixing the liquid medicine (1) and the liquid medicine (2), and adding quinoline yellow and banana flavor corrective.
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| CN103108635A (en) * | 2010-06-30 | 2013-05-15 | J·乌里亚奇·Y股份有限公司 | Liquid formulations of rupatadine fumarate |
| CN112315903A (en) * | 2020-11-20 | 2021-02-05 | 北京华氏开元医药科技有限公司 | Rupatadine fumarate oral solution and preparation method thereof |
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| CN103108635A (en) * | 2010-06-30 | 2013-05-15 | J·乌里亚奇·Y股份有限公司 | Liquid formulations of rupatadine fumarate |
| CN112315903A (en) * | 2020-11-20 | 2021-02-05 | 北京华氏开元医药科技有限公司 | Rupatadine fumarate oral solution and preparation method thereof |
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