CN116898873A - Polyethylene glycol compound combination medicine and preparation method thereof - Google Patents
Polyethylene glycol compound combination medicine and preparation method thereof Download PDFInfo
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- CN116898873A CN116898873A CN202310922652.XA CN202310922652A CN116898873A CN 116898873 A CN116898873 A CN 116898873A CN 202310922652 A CN202310922652 A CN 202310922652A CN 116898873 A CN116898873 A CN 116898873A
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- polyethylene glycol
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- 229920001223 polyethylene glycol Polymers 0.000 title claims abstract description 85
- 239000002202 Polyethylene glycol Substances 0.000 title claims abstract description 80
- 150000001875 compounds Chemical class 0.000 title claims abstract description 35
- 239000003814 drug Substances 0.000 title abstract description 17
- 238000002360 preparation method Methods 0.000 title description 11
- 239000000203 mixture Substances 0.000 claims abstract description 63
- 239000002245 particle Substances 0.000 claims abstract description 21
- 239000000796 flavoring agent Substances 0.000 claims abstract description 20
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 239000000463 material Substances 0.000 claims abstract description 10
- 239000002518 antifoaming agent Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 30
- 235000002639 sodium chloride Nutrition 0.000 claims description 29
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 claims description 24
- 229940083037 simethicone Drugs 0.000 claims description 24
- 239000000843 powder Substances 0.000 claims description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 19
- 235000011152 sodium sulphate Nutrition 0.000 claims description 19
- 235000011164 potassium chloride Nutrition 0.000 claims description 16
- 239000001103 potassium chloride Substances 0.000 claims description 16
- 239000011780 sodium chloride Substances 0.000 claims description 15
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 12
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 claims description 12
- 229940057838 polyethylene glycol 4000 Drugs 0.000 claims description 12
- 239000002131 composite material Substances 0.000 claims description 10
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 235000003599 food sweetener Nutrition 0.000 claims description 8
- 239000003765 sweetening agent Substances 0.000 claims description 8
- 239000006068 taste-masking agent Substances 0.000 claims description 8
- 238000005550 wet granulation Methods 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 238000005070 sampling Methods 0.000 claims description 7
- 238000005303 weighing Methods 0.000 claims description 7
- 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 description 6
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 6
- 108010011485 Aspartame Proteins 0.000 claims description 6
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 claims description 6
- 239000004376 Sucralose Substances 0.000 claims description 6
- 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 description 6
- 229930006000 Sucrose Natural products 0.000 claims description 6
- 239000000605 aspartame Substances 0.000 claims description 6
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 6
- 235000010357 aspartame Nutrition 0.000 claims description 6
- 229960003438 aspartame Drugs 0.000 claims description 6
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 claims description 6
- 229940049654 glyceryl behenate Drugs 0.000 claims description 6
- 229940074045 glyceryl distearate Drugs 0.000 claims description 6
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 6
- 229940085605 saccharin sodium Drugs 0.000 claims description 6
- 229960001462 sodium cyclamate Drugs 0.000 claims description 6
- 235000019408 sucralose Nutrition 0.000 claims description 6
- 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 6
- 239000005720 sucrose Substances 0.000 claims description 6
- 239000013530 defoamer Substances 0.000 claims description 5
- 238000004806 packaging method and process Methods 0.000 claims description 5
- 238000012216 screening Methods 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 3
- 229960004793 sucrose Drugs 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 2
- 229920005989 resin Polymers 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- -1 stearyl ester Chemical class 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 206010067484 Adverse reaction Diseases 0.000 abstract description 14
- 230000006838 adverse reaction Effects 0.000 abstract description 14
- 229940079593 drug Drugs 0.000 abstract description 9
- 230000007012 clinical effect Effects 0.000 abstract description 6
- 206010000060 Abdominal distension Diseases 0.000 abstract description 3
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 230000008673 vomiting Effects 0.000 abstract description 3
- 238000003908 quality control method Methods 0.000 abstract description 2
- 238000007873 sieving Methods 0.000 abstract description 2
- 210000004916 vomit Anatomy 0.000 abstract description 2
- 239000003792 electrolyte Substances 0.000 description 15
- 239000013067 intermediate product Substances 0.000 description 13
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 210000001035 gastrointestinal tract Anatomy 0.000 description 12
- 238000004140 cleaning Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 5
- 210000000936 intestine Anatomy 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 239000012459 cleaning agent Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 241000792859 Enema Species 0.000 description 2
- 206010015137 Eructation Diseases 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 208000019790 abdominal distention Diseases 0.000 description 2
- 229910052788 barium Inorganic materials 0.000 description 2
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000007920 enema Substances 0.000 description 2
- 229940095399 enema Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000035984 Colonic Polyps Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 206010050953 Lower gastrointestinal haemorrhage Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000027687 belching Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000002052 colonoscopy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000001839 endoscopy Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940050929 polyethylene glycol 3350 Drugs 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000001779 taste bud Anatomy 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
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- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a compound composition containing polyethylene glycol, which comprises polyethylene glycol, a defoaming agent, inorganic salts and a flavoring agent, wherein the contents of the components in percentage by weight are as follows: 80 to 90 percent of polyethylene glycol, 0.1 to 0.2 percent of defoaming agent, 10 to 20 percent of inorganic salts and 0.2 to 0.3 percent of flavoring agent. The invention controls the particle size of the unnecessary components by crushing and sieving, adjusts the bulk density of each component, ensures that the bulk densities of each component are similar, and ensures the mixing uniformity and other quality control indexes of each raw material and auxiliary material of the product. Has good taste and can obviously improve the medication compliance of patients. The clinical effect is more obvious, the enteroscopy graph is clearer, and the correct diagnosis rate is higher. The adverse reaction after the administration is lower, and the adverse reaction such as vomit, abdominal distension and the like is obviously reduced.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and in particular relates to a compound composition containing polyethylene glycol and a preparation method thereof.
Background
Polyethylene glycol is a high molecular polymer polymerized by long-chain ethylene oxide, and the polyethylene glycol with the relative molecular mass exceeding 3000 can not be absorbed in intestinal tracts, and the intestinal tracts lack enzymes for degrading polyethylene glycol 4000, so that the polyethylene glycol has the effects of relaxing bowels and cleaning intestines, and polyethylene glycol 3350 and 4000 are commonly used clinically. The action mechanism of the oral liquid is that after the oral liquid enters a human body, hydrogen bonds can be formed with water molecules to keep water in colon, the water content of the excrement is increased, the excrement is softened, the volume and the weight of the excrement are recovered to be normal, and the final completion of the excrement is promoted, so that constipation symptoms are improved; enteroscopy, barium enema and other pre-examination intestinal tract cleaning preparations. The intestinal tract cleaning agent is widely used clinically, and has large dosage in various departments. Clean intestinal tract is an important condition for successful operation, reduced complications, and successful enteroscopy, barium X-ray enema, CT examination, B-ultrasound and other examinations, improving diagnosis accuracy. Because polyethylene glycol powder has the characteristics of safety, effectiveness, convenience for patients to accept and convenience for use, the polyethylene glycol powder is widely applied to clinic in some countries at present.
Simethicone and simethicone are clinically commonly used medical defoamers, and because of small surface tension, the surface tension of bubbles can be changed to break the bubbles, so that bubbles in the gastrointestinal tract are eliminated, and a colonoscopy intestinal preparation guide of the European gastrointestinal endoscopy society 2019 proposes that the generation of bubbles can be effectively reduced by properly applying simethicone or simethicone in the intestinal preparation process, so that the intestinal preparation quality is improved, the comfort level of a patient in examination is improved, and adverse reactions such as abdominal distension and eructation after the endoscopic examination of the patient are reduced.
At present, most of polyethylene glycol intestine cleaning agents are added with sweeteners to improve taste, but when patients take the products, the taste is still bad, so that the compliance of the patients is poor, and therefore, the taste cannot be obviously improved by simply adopting the sweeteners.
The lipid auxiliary material is a high molecular polymer, contains ionized and activated groups, and can be mutually adsorbed with ionic medicines by electrostatic interaction. Because the saliva secreted by the oral cavity is less, the ion concentration is low, the retention time of lipid auxiliary materials in the oral cavity is short when the oral administration is carried out, and the medicine enters the stomach after being desorbed, so that the bad taste of the medicine can be effectively covered by isolating the contact of the medicine and taste buds.
Because polyethylene glycol, inorganic salts and flavoring agents are mainly because of different particle sizes and densities, the polyethylene glycol, the inorganic salts and the flavoring agents are difficult to mix uniformly, so that the dosage of each component in the produced polyethylene glycol electrolyte powder small package is different, the quality is uncontrollable, and the domestic medicine manufacturer usually comprises A, B two packages or A, B, C three packages, such as constant Kang Zhengqing full intestine lavage liquid, the powder packaged in a complete dosage is divided into 3 small packages, A comprises 0.74g of potassium chloride and 1.68g of sodium bicarbonate because the production process is immature and the equipment is behind; b comprises 1.46g of sodium chloride and 5.68g of sodium sulfate; c comprises 60g of polyethylene glycol 4000, and is dissolved, diluted and taken in a container just before use. The problems brought by the multi-package powder are (1) complicated production procedures, energy consumption and environmental protection; (2) The packaging is more, the packaging quantity is uneven, the quality is uncontrollable, and the yield is low; (4) When in use, the packaging bags are too many, so that the use is troublesome and waste is easily caused;
in view of the above-mentioned prior art, the present inventors have made an effort to produce an intestine-cleansing composition and a method for producing the same based on the expertise of designing and manufacturing, which can improve the existing intestine-cleansing agent, so that the compliance of the patient with the medicine is better, the clinical effect is more excellent, the adverse reaction of the medicine is less, and through continuous research and trial and error, the invention having practical value is finally produced.
Disclosure of Invention
The invention mainly aims at improving the existing polyethylene glycol intestine cleaning agent, and provides a novel polyethylene glycol-containing compound composition and a preparation method thereof.
The invention aims at solving the technical problems by adopting the following technical scheme.
The invention provides a compound composition containing polyethylene glycol, which comprises polyethylene glycol, a defoaming agent, inorganic salts and a flavoring agent, wherein the contents of the components in percentage by weight are as follows: 80 to 90 percent of polyethylene glycol, 0.1 to 0.2 percent of defoaming agent, 10 to 20 percent of inorganic salts and 0.2 to 0.3 percent of flavoring agent.
Wherein the polyethylene glycol is selected from polyethylene glycols having an average molecular weight of 3000 to 4500.
The compound composition containing polyethylene glycol, wherein the polyethylene glycol is selected from polyethylene glycol with average molecular weight of 4000.
The compound composition containing polyethylene glycol, wherein the defoamer is one or a mixture of simethicone and simethicone.
The compound composition containing polyethylene glycol, wherein the inorganic salt is selected from one or a mixture of sodium sulfate, sodium chloride, potassium chloride and sodium bicarbonate.
The polyethylene glycol-containing compound composition comprises a taste masking agent and a sweetener.
The taste masking agent in the taste masking agent is selected from one or a mixture of the group consisting of the polepiecene resin, the glyceryl monostearate, the stearyl, the glyceryl behenate and the glyceryl distearate.
The compound composition containing polyethylene glycol, wherein the sweetener in the flavoring agent is selected from one or a mixture of saccharin sodium, sucrose, sodium cyclamate, aspartame and sucralose.
The aim and the technical problems of the invention are further realized by adopting the following technical measures.
The invention also provides a method for preparing the compound composition containing polyethylene glycol, which comprises the following steps:
(1) Pretreatment of raw materials and auxiliary materials: respectively crushing and screening polyethylene glycol, inorganic salts and flavoring agents, wherein the D90 particle size of the crushed and screened polyethylene glycol is 170-190 mu m, the D90 particle size of the inorganic salts is 150-180 mu m, and the D90 particle size of the flavoring agents is 120-160 mu m;
(2) Premixing: weighing inorganic salt, defoamer and corrective according to the prescription amount, and mixing in a wet granulation mixer;
(3) Total mixing: weighing the polyethylene glycol 4000 and the premixed powder according to the prescription amount, putting the mixture into a hopper-type mixer for mixing, and sampling and detecting the content of an intermediate;
(4) And (5) subpackaging: after the loading is calculated according to the content of the intermediate, split charging by adopting a composite film;
the preparation method comprises the steps of (2) mixing for 10-30 minutes at a mixing speed of 80-120 rpm;
the preparation method comprises the steps of (3) mixing for 15-45 minutes at a mixing speed of 6-9 rpm;
the beneficial technical effects of the invention are as follows: the invention is an improvement on the prior art, and the raw materials and the auxiliary materials used by the invention are all of medicinal grade, and have no side effect on human body safety. The invention controls the particle size of the unnecessary components by crushing and sieving, adjusts the bulk density of each component, ensures that the bulk densities of each component are similar, and ensures the mixing uniformity and other quality control indexes of each raw material and auxiliary material of the product. Has good taste and can obviously improve the medication compliance of patients. The clinical effect is more obvious, the enteroscopy graph is clearer, and the correct diagnosis rate is higher. The adverse reaction after the administration is lower, and the adverse reaction such as vomit, abdominal distension and the like is obviously reduced.
In conclusion, the compound composition containing polyethylene glycol has good clinical effect and less adverse reaction, has a plurality of advantages and use values, has higher technical innovation in the aspects of prescription design and preparation technology and the like, has obvious improvement in medication compliance and clinical effect of patients, obviously reduces adverse reaction of medication, has wide use value, is novel in prescription, has technical innovation and is a new design which is economical and applicable.
Detailed Description
In order to make the technical means of the present invention implemented and innovative features, the technical invention will be apparent and it will be apparent to those skilled in the art that it is intended to be more specifically defined and described in the following description of embodiments of the invention and that it is intended to be limiting in some, but not in all, respects only the embodiments of the invention and, therefore, all other embodiments of the invention which are obvious to those skilled in the art without the benefit of the teachings of this invention are intended to be within the scope of the invention.
The compound composition containing polyethylene glycol comprises polyethylene glycol, a defoaming agent, inorganic salts and a flavoring agent, wherein the contents of the components in percentage by weight are as follows: 80 to 90 percent of polyethylene glycol, 0.1 to 0.2 percent of defoaming agent, 10 to 20 percent of inorganic salts and 0.2 to 0.3 percent of flavoring agent. Preferably, the method comprises the steps of,
the polyethylene glycol is selected from polyethylene glycols having an average molecular weight of 3000 to 4500, more preferably from polyethylene glycols having an average molecular weight of 4000. The defoamer is selected from simethicone or a mixture thereof. The inorganic salt is selected from one or a mixture of sodium sulfate, sodium chloride, potassium chloride and sodium bicarbonate. The taste masking agent comprises one or a mixture of a taste masking agent and a sweetener, wherein the taste masking agent is selected from the group consisting of polapride, glyceryl monostearate, stearyl, glyceryl behenate and glyceryl distearate, and the sweetener is selected from the group consisting of saccharin sodium, sucrose, sodium cyclamate, aspartame and sucralose.
The method for preparing the compound composition containing polyethylene glycol comprises the following steps:
(1) Pretreatment of raw materials and auxiliary materials: respectively crushing and screening polyethylene glycol, inorganic salts and flavoring agents, wherein the D90 particle size of the crushed and screened polyethylene glycol is 170-190 mu m, the D90 particle size of the inorganic salts is 150-180 mu m, and the D90 particle size of the flavoring agents is 120-160 mu m; (2) premixing: weighing inorganic salt, defoamer and corrective according to the prescription amount, and mixing in a wet granulation mixer; (3) total mixing: weighing the polyethylene glycol 4000 and the premixed powder according to the prescription amount, putting the mixture into a hopper-type mixer for mixing, and sampling and detecting the content of an intermediate; (4) sub-packaging: after the loading is calculated according to the content of the intermediate, split charging by adopting a composite film;
d90 according to the present invention refers to the particle size corresponding to the cumulative particle size fraction of the material components when deployed to% and has the physical meaning that the particle size is less than 90% of the total particles.
The specific implementation method for preparing the compound composition containing polyethylene glycol according to the proportion and the method is described in detail below.
Example 1
Weighing 640kg of polyethylene glycol 4000,7.5kg of potassium chloride, 16.8kg of sodium bicarbonate, 14.6kg of sodium chloride, 57kg of sodium sulfate, 1.5kg of simethicone, 3kg of polacrilex sodium, 1kg of saccharin sodium, crushing and screening to ensure that the D90 particle size meets the requirement, firstly placing the potassium chloride, the sodium bicarbonate, the sodium chloride, the sodium sulfate, the simethicone, the polrvinyl sodium and the saccharin sodium into a wet granulation mixer, mixing for 20 minutes at a speed of 100 revolutions per minute, then placing the mixture and the polyethylene glycol 4000 into a hopper mixer, mixing for 30 minutes at a speed of 8 revolutions per minute, sampling to detect the content of an intermediate product, calculating the loading amount according to the content of the intermediate product after qualification, subpackaging into a composite film, and heating and sealing, wherein each bag contains 64g of polyethylene glycol (4000), 0.75g of potassium chloride, 1.68g of sodium bicarbonate, 1.46g of sodium chloride, 5.7g of sodium sulfate, 0.15g of simethicone, 0.3g of polrvinyl sodium, and 0.1g of saccharin sodium.
Example 2
640kg of polyethylene glycol 4000, 16.8kg of sodium bicarbonate, 14.6kg of sodium chloride, 57kg of sodium sulfate, 1.0kg of simethicone, 2kg of glyceryl distearate and 1.5kg of aspartame are crushed and screened to enable the D90 particle size to meet the requirement, firstly, the sodium bicarbonate, the sodium chloride, the sodium sulfate, the simethicone, the glyceryl distearate and the aspartame are placed in a wet granulation mixer to be mixed for 15 minutes at a speed of 90 revolutions per minute, then, the mixture and the polyethylene glycol 4000 are placed in a hopper mixer to be mixed for 45 minutes at a speed of 6 revolutions per minute, the content of an intermediate product is sampled and detected, after the intermediate product is qualified, the mixture is split into a composite film according to the calculated content of the intermediate product, and the composite film is sealed by heating, wherein each bag contains 64g of polyethylene glycol (4000), 1.68g of sodium bicarbonate, 1.46g of sodium chloride, 5.7g of sodium sulfate, 0.1g of simethicone, 0.2g of glyceryl distearate and 0.15g of aspartame.
Example 3
640kg of polyethylene glycol 4000,7.5kg of potassium chloride, 16.8kg of sodium bicarbonate, 57kg of sodium sulfate, 1.0kg of simethicone, 1.0kg of glyceryl behenate and 1.8kg of sodium cyclamate are weighed, crushed and screened to enable the D90 particle size to meet the requirement, firstly, the potassium chloride, the sodium bicarbonate, the sodium sulfate, the simethicone, the glyceryl behenate and the sodium cyclamate are placed in a wet granulation mixer to be mixed for 30 minutes at a speed of 110 revolutions per minute, then the mixture and the polyethylene glycol 4000 are placed in a hopper mixer to be mixed for 25 minutes at a speed of 7 revolutions per minute, the content of an intermediate product is detected by sampling, after the intermediate product is qualified, the mixture is packaged in a composite film according to the calculated content of the intermediate product, and the mixture is sealed by heating, wherein each bag contains 64g of polyethylene glycol (4000), 0.75g of potassium chloride, 1.68g of sodium bicarbonate, 5.7g of sodium sulfate, 0.1g of simethicone, 0.1g of glyceryl behenate and 0.18g of sodium cyclamate.
Example 4
640kg of polyethylene glycol 4000,7.5kg of potassium chloride, 14.6kg of sodium chloride, 57kg of sodium sulfate, 1.5kg of simethicone, 3kg of stearin and 0.8kg of sucralose are weighed, crushed and screened to enable the D90 particle size to meet the requirement, firstly, the potassium chloride, the sodium sulfate, the simethicone, the stearin and the sucralose are placed into a wet granulation mixer to be mixed for 15 minutes at a speed of 80 revolutions per minute, then the mixture and the polyethylene glycol 4000 are placed into a hopper mixer to be mixed for 45 minutes at a speed of 9 revolutions per minute, sampling is carried out to detect the content of an intermediate product, and after the mixture is qualified, the mixture is split into a composite film according to the calculated content of the intermediate product, and the composite film is heated and sealed, wherein each bag contains 64g of polyethylene glycol (4000), 0.75g of potassium chloride, 1.46g of sodium chloride, 5.7g of sodium sulfate, 0.15g of simethicone, 0.3g of stearin and 0.1g of sucralose.
Example 5
640kg of polyethylene glycol 4000,7.5kg of potassium chloride, 16.8kg of sodium bicarbonate, 14.6kg of sodium chloride, 57kg of sodium sulfate, 1.2kg of simethicone, 1.5kg of glycerin monostearate and 3kg of sucrose are weighed, crushed and screened to enable the D90 particle size to meet the requirement, firstly, the potassium chloride, the sodium bicarbonate, the sodium chloride, the sodium sulfate, the simethicone, the glycerin monostearate and the sucrose are placed in a wet granulation mixer to be mixed for 10 minutes at the speed of 120 revolutions per minute, then the mixture and the polyethylene glycol 4000 are placed in a hopper mixer to be mixed for 30 minutes at the speed of 8 revolutions per minute, the content of an intermediate product is detected by sampling, after the intermediate product is qualified, the mixture is calculated and filled into a composite film according to the content of the intermediate product, and the mixture is packaged, and the mixture is sealed by heating, wherein each bag contains 64g of polyethylene glycol (4000), 0.75g of potassium chloride, 1.68g of sodium bicarbonate, 1.46g of sodium chloride, 5.7g of sodium sulfate, 0.12g of simethicone, 0.5g of glycerin monostearate and 0.3g of sucrose.
Comparative example 1
Commercially available polyethylene glycol electrolyte powder
Test example 1: clinical effect evaluation of polyethylene glycol electrolyte powder
Test materials: the polyethylene glycol-containing compound composition of example 1 of the present invention was compared with a commercially available polyethylene glycol electrolyte powder.
Grouping: 228 patients were subjected to a randomized clinical trial of intestinal tract cleaning, of 228, 110 men, 118 women, age 35-55 years, divided into two groups a and B, wherein group a: male 56, female 58, group B: 54 men and 60 women, 114 in each group.
Disease category: 46 cases of ulcerative colitis, 55 cases of colonic polyps, 102 cases of chronic nonspecific colitis, and 25 cases of lower gastrointestinal bleeding.
The test method comprises the following steps: the group A adopts the compound composition containing polyethylene glycol in the embodiment 1, the group B adopts the polyethylene glycol electrolyte powder sold in the market, the gender, the age and the disease types of the two groups are compared, the difference has no significance (the P is more than 0.05), and the patients have no symptoms of abdominal pain, abdominal distention, nausea and the like before taking the compound composition.
The polyethylene glycol electrolyte powder was taken according to the polyethylene glycol electrolyte powder instructions, and both the polyethylene glycol electrolyte powder of example 1 and the commercially available polyethylene glycol electrolyte powder were dissolved in warm water and stirred to dissolve completely, and 2000ml (2 bags) were taken every day before the examination and at night, and 2000ml (2 bags) were taken again 3 to 4 hours before the examination.
Judgment standard:
(1) The effect of cleaning the intestines: the evaluation was performed using the wortmann scale scoring criteria, which is one of the internationally used intestinal readiness quality scoring criteria.
(2) Common adverse reactions: nausea, abdominal pain, abdominal distention, vomiting, belching, etc.
(3) Patient compliance with medication: taste acceptance degree, and medication willingness.
Experimental results: the intestinal cleaning effect, adverse reaction and medication compliance of each patient were observed and recorded, and the experimental results are shown in tables 1, 2 and 3.
Table 1: statistics of bowel cleansing effect
Remarks: the lower the score, the better the bowel cleansing effect.
As can be seen from the statistics of the intestinal tract cleaning effect of Table 1, the polyethylene glycol-containing compound composition of example 1 of the present invention had a ratio of "0" to 61.4%, a ratio of "1" to 25.4%, a ratio of "0" to 1 "to 86.8%, a ratio significantly higher than the ratio of" 0 "to 44.7%," 1 "to 19.3%," 0 "to 1" to 64.0%, the intestinal tract cleaning effect of the polyethylene glycol-containing compound composition of the embodiment 1 of the invention is improved by at least 30% compared with that of the polyethylene glycol electrolyte powder on the market, no matter the excellent state with the score of 0 or the good state with the score of 1, and the intestinal tract cleaning effect is statistically significant (P is more than 0.05).
Meanwhile, the comprehensive score of the polyethylene glycol-containing compound composition of the embodiment 1 on the intestinal tract cleaning effect of a patient is 68 minutes, which is obviously higher than that of the polyethylene glycol electrolyte powder sold in the market, and the comprehensive score of the polyethylene glycol-containing compound composition is 128 minutes, and the polyethylene glycol-containing compound composition has statistical significance (P is more than 0.05), so that the intestinal tract cleaning effect of the polyethylene glycol-containing compound composition is better than that of the polyethylene glycol electrolyte powder sold in the market.
Table 2: adverse reaction statistics table
Remarks: patients may experience several adverse effects at the same time.
As can be seen from the results in Table 2, the total adverse reaction rate of the polyethylene glycol electrolyte powder taken on the market is significantly higher than the total adverse reaction rate of 8.4% of the polyethylene glycol-containing compound composition taken in example 1 of the invention, and the product has a statistical significance (P is more than 0.05), and overall, the adverse reaction rate of the product is less, so that the product is suitable for patients to take.
Table 3: patient compliance statistics
As can be seen from the results in Table 3, the patients take the polyethylene glycol-containing compound composition of example 1 of the present invention, wherein the ratio of the good taste is 39.5%, the ratio of the good taste and the good taste is up to 72%, which is much higher than the ratio of the good taste of the patients taking the commercial polyethylene glycol electrolyte powder by 10.5%, the ratio of the good taste and the good taste is 30.7%, which has statistical significance (P > 0.05), which indicates that the taste and the medication compliance of the product of the present invention are higher than those of the commercial polyethylene glycol electrolyte powder.
The foregoing disclosure is merely illustrative of the preferred embodiments of the present invention, and is not intended to limit the invention in any way, and any person skilled in the art may make any changes or modifications to the above-described embodiments without departing from the scope of the present invention.
Claims (11)
1. A compound composition containing polyethylene glycol, which is characterized in that: the composition comprises polyethylene glycol, a defoaming agent, inorganic salts and a flavoring agent, wherein the contents of the components in percentage by weight are as follows: 80 to 90 percent of polyethylene glycol, 0.1 to 0.2 percent of defoaming agent, 10 to 20 percent of inorganic salts and 0.2 to 0.3 percent of flavoring agent.
2. The compound composition according to claim 1, wherein: the polyethylene glycol is selected from polyethylene glycols having an average molecular weight of 3000 to 4500.
3. The compound composition of claim 1, wherein the polyethylene glycol is selected from polyethylene glycols having an average molecular weight of 4000.
4. The compound composition according to claim 1, wherein: the defoamer is one or a mixture of simethicone and simethicone.
5. The compound composition according to claim 1, wherein the inorganic salt is selected from one of sodium sulfate, sodium chloride, potassium chloride, sodium bicarbonate or a mixture thereof.
6. The compound composition according to claim 1, wherein: the flavoring agent comprises a taste masking agent and a sweetener.
7. The compound composition according to claim 1, wherein: the taste masking agent in the taste correction agent is selected from one or a mixture of the substances selected from the group consisting of polepiecene phosphate resin, glyceryl monostearate, stearyl ester, glyceryl behenate and glyceryl distearate.
8. The compound composition according to claim 1, wherein: the sweetener in the flavoring agent is selected from one or a mixture of saccharin sodium, sucrose, sodium cyclamate, aspartame and sucralose.
9. A process for preparing the composition of any one of claims 1 to 8, characterized in that: the method comprises the following steps:
1) Pretreatment of raw materials and auxiliary materials: respectively crushing and screening polyethylene glycol, inorganic salts and flavoring agents, wherein the D90 particle size of the crushed and screened polyethylene glycol is 170-190 mu m, the D90 particle size of the inorganic salts is 150-180 mu m, and the D90 particle size of the flavoring agents is 120-160 mu m;
2) Premixing: weighing inorganic salt with the prescription amount, a defoaming agent and a flavoring agent, and mixing in a wet granulation mixer to obtain premixed powder;
3) Total mixing: weighing the polyethylene glycol 4000 and the premixed powder according to the prescription amount, putting the mixture into a hopper-type mixer for mixing, and sampling and detecting the content of an intermediate;
4) And (5) subpackaging: and (5) after the loading is calculated according to the content of the intermediate, packaging by adopting a medicinal composite film.
10. The method of manufacturing according to claim 9, wherein: the mixing time in the step (2) is 10-30 minutes, and the mixing rotating speed is 80-120 revolutions per minute.
11. The method of manufacturing according to claim 9, wherein: in the step (3), the mixing time is 15-45 minutes, and the mixing rotating speed is 6-9 revolutions per minute.
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