WO2022227116A1 - 一种罗红霉素胶囊的制备方法 - Google Patents
一种罗红霉素胶囊的制备方法 Download PDFInfo
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- WO2022227116A1 WO2022227116A1 PCT/CN2021/093192 CN2021093192W WO2022227116A1 WO 2022227116 A1 WO2022227116 A1 WO 2022227116A1 CN 2021093192 W CN2021093192 W CN 2021093192W WO 2022227116 A1 WO2022227116 A1 WO 2022227116A1
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- WIPO (PCT)
- Prior art keywords
- roxithromycin
- parts
- weight
- preparation
- coating
- Prior art date
Links
- RXZBMPWDPOLZGW-XMRMVWPWSA-N (E)-roxithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N/OCOCCOC)/[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 RXZBMPWDPOLZGW-XMRMVWPWSA-N 0.000 title claims abstract description 63
- 229960005224 roxithromycin Drugs 0.000 title claims abstract description 62
- 239000002775 capsule Substances 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title abstract description 10
- 238000000576 coating method Methods 0.000 claims abstract description 42
- 239000011248 coating agent Substances 0.000 claims abstract description 41
- 238000002360 preparation method Methods 0.000 claims abstract description 19
- 239000000230 xanthan gum Substances 0.000 claims abstract description 18
- 229920001285 xanthan gum Polymers 0.000 claims abstract description 18
- 229940082509 xanthan gum Drugs 0.000 claims abstract description 18
- 235000010493 xanthan gum Nutrition 0.000 claims abstract description 18
- 239000000463 material Substances 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 239000003085 diluting agent Substances 0.000 claims abstract description 11
- 238000002156 mixing Methods 0.000 claims abstract description 8
- 230000000181 anti-adherent effect Effects 0.000 claims abstract description 7
- 229920005596 polymer binder Polymers 0.000 claims abstract description 7
- 239000002491 polymer binding agent Substances 0.000 claims abstract description 7
- 239000000725 suspension Substances 0.000 claims description 27
- 239000000853 adhesive Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 claims description 14
- 229920003149 Eudragit® E 100 Polymers 0.000 claims description 12
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical group COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 claims description 12
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 230000001070 adhesive effect Effects 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 239000004925 Acrylic resin Substances 0.000 claims description 9
- 229920000178 Acrylic resin Polymers 0.000 claims description 9
- 229920000642 polymer Polymers 0.000 claims description 9
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 8
- 229920001577 copolymer Polymers 0.000 claims description 8
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000011049 filling Methods 0.000 claims description 6
- 239000000454 talc Substances 0.000 claims description 6
- 229910052623 talc Inorganic materials 0.000 claims description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 229930006000 Sucrose Natural products 0.000 claims description 5
- 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 5
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 238000000889 atomisation Methods 0.000 claims description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 5
- 238000003908 quality control method Methods 0.000 claims description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000005720 sucrose Substances 0.000 claims description 5
- 230000004584 weight gain Effects 0.000 claims description 5
- 235000019786 weight gain Nutrition 0.000 claims description 5
- 239000000811 xylitol Substances 0.000 claims description 5
- 235000010447 xylitol Nutrition 0.000 claims description 5
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 5
- 229960002675 xylitol Drugs 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 4
- 238000012216 screening Methods 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 239000004386 Erythritol Substances 0.000 claims description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 2
- 235000019414 erythritol Nutrition 0.000 claims description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 2
- 229940009714 erythritol Drugs 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 229960001855 mannitol Drugs 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical group O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims 1
- 235000012222 talc Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 20
- 238000004090 dissolution Methods 0.000 abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 15
- 235000019658 bitter taste Nutrition 0.000 abstract description 12
- 239000006185 dispersion Substances 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 239000003960 organic solvent Substances 0.000 abstract description 7
- 239000003995 emulsifying agent Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 239000003911 antiadherent Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 18
- 229940079593 drug Drugs 0.000 description 13
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 10
- 229960003276 erythromycin Drugs 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000007922 dissolution test Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 3
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000606161 Chlamydia Species 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 241000589875 Campylobacter jejuni Species 0.000 description 1
- 208000007190 Chlamydia Infections Diseases 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 241000186227 Corynebacterium diphtheriae Species 0.000 description 1
- -1 Cyclic lactone Chemical class 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 206010024179 Legionella infections Diseases 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 206010028470 Mycoplasma infections Diseases 0.000 description 1
- 241000202934 Mycoplasma pneumoniae Species 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000606834 [Haemophilus] ducreyi Species 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 208000028512 chlamydia infectious disease Diseases 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012088 reference solution Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000001507 sample dispersion Methods 0.000 description 1
- 239000011378 shotcrete Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
Definitions
- the invention relates to the technical field of pharmaceutical preparations, in particular to a preparation method of roxithromycin capsules.
- Roxithromycin is a macrolide antibiotic that mainly acts on Gram-positive bacteria, anaerobic bacteria, chlamydia and mycoplasma. Its in vitro antibacterial effect is similar to that of erythromycin.
- the activity against Streptococcus, Haemophilus ducreyi, Chlamydia trachomatis, Mycoplasma pneumoniae, oral or vaginal anaerobic bacteria is similar to that of erythromycin; the effect on Campylobacter, Bacillus pertussis and Haemophilus influenzae is not as good as erythromycin; Mycobacterium tuberculosis, most atypical mycobacteria, Campylobacter jejuni, Bacillus diphtheriae, Pasteurella haemorrhagicus also have inhibitory effects; no antibacterial activity against G bacteria.
- Some bacteria have cross-resistance to erythromycin and this product, and this product is particularly effective for mycoplasma, chlamydia and Legionella infections.
- the concentration of antibacterial effect in vivo is 1 to 4 times stronger than that of erythromycin.
- the commonly used oral roxithromycin dosage forms include tablets, capsules, granules and the like.
- Existing capsules are not suitable for children, the elderly and patients with dysphagia, and have great limitations. Some of them need to be taken apart for convenience of taking, and the medicines inside need to be taken with water.
- roxithromycin is a large Cyclic lactone antibiotics have a very bitter taste, and it is difficult to take the drug directly when it is poured out. Roxithromycin has poor water solubility. The bioavailability of the drug is not high.
- the existing process uses an organic solvent to coat the granules before filling the capsules, and then adds a flavoring agent and mixes them evenly before filling. Mask the bitter taste of the drug and improve the dissolution rate of the drug, but this method uses many excipients and cannot improve the dissolution rate of the drug better.
- the object of the present invention is to provide a preparation method of a Roxithromycin capsule for the deficiencies of the prior art, which can be taken directly and the capsule can be disassembled as required, and the medicine inside can be taken with water, and a polymer adhesive is used.
- the aqueous dispersion of Eudragit E100 (butyl methacrylate: dimethylaminoethyl methacrylate: methyl methacrylate 20:40:20 copolymer) replaced the traditional organic solvent coating, and obtained high dissolution and stable Roxithromycin capsules with better properties save the cost of raw materials, are suitable for industrial production, reduce the use of coating materials and emulsifiers, save production costs, are conducive to safe production and environmental protection, and can mask the bitter taste of drugs At the same time, it can improve the dissolution rate of the drug, and it is suitable for a wide range of people and has less limitations.
- a preparation method of roxithromycin capsule comprising the steps:
- S5 Mix the coating in S4 with xanthan gum, dry, sieve the resulting granules, and then fill capsules.
- the present invention includes the following parts by weight: 8-20 parts by weight of roxithromycin, 2-8 parts by weight of xanthan gum, 20-30 parts by weight of polymer adhesive, 100-150 parts by weight of diluent, Adhesive 25-50 parts by weight.
- the present invention includes the following parts by weight: 15 parts by weight of roxithromycin, 4 parts by weight of xanthan gum, 25 parts by weight of polymer adhesive, 130 parts by weight of diluent, and 38 parts by weight of anti-adhesive.
- the diluent is one or a mixture of sucrose, mannitol, xylitol and erythritol.
- the polymer binder is one or more of Eudragit E100, No. II acrylic resin, No. III acrylic resin, No. IV acrylic resin, sodium carboxymethyl cellulose, and the Eudragit E100 It is a copolymer of butyl methacrylate: dimethylaminoethyl methacrylate: methyl methacrylate 20:40:20.
- the polymer binder is Eudragit E100.
- the anti-sticking agent is one of talc, magnesium stearate or glycerol monostearate.
- the anti-sticking agent is talc.
- the parameters of the fluidized bed granulator are, the air volume is 60m 3 /h, the inlet air temperature is 35-50°C, the atomization pressure is 1.5bar, the material temperature is 30-40°C, and the outlet air temperature is 30-40°C. 55°, shotcrete flow 10g/min, nozzle hot air temperature 120°.
- Eudragit E100 (butyl methacrylate: dimethylaminoethyl methacrylate: methyl methacrylate 20:40:20 copolymer) is used as a polymer adhesive, and this is sprayed as a coating solution on The surface of roxithromycin forms a coating, which breaks the traditional use of coating materials and emulsifiers for coating, saving the use of raw materials, and the coating formed by the polymer binder can cover up the bitter taste of the drug, thus The dosage of correctives and sweeteners can be reduced, the use of auxiliary materials is greatly reduced, and the production cost is saved.
- the capsules prepared by the present invention can be taken directly, and the capsules can be disassembled and the medicines in the capsules can be taken with water according to the needs.
- Eudragit E100 (butyl methacrylate: dimethylaminoethyl methacrylate: methyl methacrylate 20: 40: 20 copolymer) aqueous dispersion is a polymer latex particle with a particle size of 0.01 to 0.1 microns. Dispersion in water, the polymer content is 30% (w/w), the viscosity is low, and it is easy to spray coating operation. During the film-forming process, the latex particles form a stacked layer, and as the water evaporates, the surface tension increases, making the colloidal particles Tightly aggregated to form a film in an environment above the minimum film-forming temperature. The resistance of this film to water penetration is better than that of the film formed with an organic solvent coating solution.
- the evaporation of the solvent in the organic solvent coating solution requires consumption due to the heat of solvation. Compared with the water evaporation in the water dispersion, it has more energy, and the latter has a high solid content, so the energy consumption of the water dispersion coating is lower, which is conducive to saving production costs and is suitable for industrial production.
- the coating liquid sprayed on the surface of the drug becomes viscous with the evaporation of the solvent.
- Adding an appropriate amount of anti-adhesive agent to the coating liquid can reduce the viscosity, prevent the particles from sticking to each other, and improve the coating effect.
- a preparation method of roxithromycin dry suspension is made into 1000 bags of the following raw and auxiliary materials:
- Eudragit E100 (butyl methacrylate: dimethylaminoethyl methacrylate: methyl methacrylate 20:40:20 copolymer) 20g;
- the suspension is formed into atomized droplets, which are slowly sprayed on the surface of the fully mixed mixture, and subjected to fluidized bed granulation to obtain a roxithromycin coating, and the quality control of the coating weight gain is 2-4%;
- step e mixing the coating in step d with xanthan gum, drying, screening the obtained granules, and then filling capsules.
- a preparation method of roxithromycin dry suspension is made into 1000 bags of the following raw and auxiliary materials:
- the suspension is formed into atomized droplets, which are slowly sprayed on the surface of the fully mixed mixture, and subjected to fluidized bed granulation to obtain a roxithromycin coating, and the quality control of the coating weight gain is 2-4%;
- step e mixing the coating in step d with xanthan gum, drying, screening the obtained granules, and then filling capsules.
- a preparation method of roxithromycin dry suspension is made into 1000 bags of the following raw and auxiliary materials:
- the suspension is formed into atomized droplets, which are slowly sprayed on the surface of the fully mixed mixture, and subjected to fluidized bed granulation to obtain a roxithromycin coating, and the quality control of the coating weight gain is 2-4%;
- step e mixing the coating in step d with xanthan gum, drying, screening the obtained granules, and then filling capsules.
- the roxithromycin capsules prepared in the above-mentioned examples were disassembled respectively, and the medicine inside was given to 60 volunteers for trial use. In 15ml of water, after 10min, each volunteer evaluated each sample in turn, took 1ml of the sample dispersion for 20s, then spit it out, evaluated the level of bitterness, rinsed the mouth, and evaluated another sample according to the above method. The results are shown in Table 1.
- Example 2 Example 3 extremely bitter 0 0 0 A bit bitter, acceptable 35% 25% 40% bitter taste 42% 32% 26% not bitter at all 0 0 0
- the medicine in the Roxithromycin capsule of embodiment 1-3 adopts water dispersion as coating liquid to carry out coating to Roxithromycin and the medicine in the Roxithromycin capsule of listing adopts Compared with the organic solvent used as the coating liquid for coating, the bitter taste of the roxithromycin capsules in Examples 1-3 was masked.
- Example 1 98.65%
- Example 2 96.36%
- Example 3 97.21%
- the capsules prepared according to the present invention show good dissolution behavior, and the dissolution rate of 30min is greater than 90%, indicating that the bitterness of roxithromycin is well masked within this range, and its dissolution rate Not affected.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (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
本发明公开了一种罗红霉素胶囊的制备方法，包括如下重量份：罗红霉素8-20重量份，黄原胶2-8重量份，高分子黏合剂20-30重量份，稀释剂100-150重量份，抗粘剂25-50重量份。本发明即可直接服用下去又可根据需要将胶囊拆开将里面的药物冲水服用，利用高分子黏合剂的水分散体代替传统的有机溶剂包衣，获得了溶出度高，稳定性较好的罗红霉素胶囊，节省了原料成本，适于工业化生产，减少对包衣材料和乳化剂的使用，节约生产成本，有利于安全生产和环境保护，能对药物的苦味进行掩盖的同时又能提高药物的溶出度，适用人群范围较广，局限性较小。
Description
本发明涉及药物制剂技术领域，具体涉及一种罗红霉素胶囊的制备方法。
罗红霉素为大环内酯类抗生素，主要作用于革兰氏阳性菌、厌氧菌、衣原体和支原体等。其体外抗菌作用与红霉素类似。对链球菌、杜克雷嗜血杆菌、沙眼衣原体、肺炎支原体、口腔或***厌氧菌等的活性与红霉素类似；对弯曲杆菌、百日咳杆菌及流感嗜血杆菌的作用不如红霉素类；对结核分歧杆菌、大部分非典型性分枝杆菌、空肠弯曲菌、白喉杆菌、出血败血性巴斯德菌也有抑制作用；对G菌无抗菌活性。某些细菌对红霉素和本品有交叉耐药性，本品对支原体、衣原体及军团菌感染特别有效。体内抗菌作用浓度比红霉素强1～4倍。
目前常用的口服罗红霉素剂型有片剂、胶囊剂、颗粒剂等。现有的胶囊剂不适合儿童、老年人和吞咽困难的病人服用，局限性较大，有些为了服用方便，需要将胶囊拆开将里面的药物用水充服用下去，但由于罗红霉素属于大环内酯类抗生素，味道极苦，直接将里面的药物倒出来服用时很难服用下去，且罗红霉素水溶解性差，倒在水中时往往溶出度较低，不易溶解，造成服用下去时药物的生物利用度不高，为了解决味苦以及溶出度问题，现有的工艺在灌装胶囊前采用有机溶剂对颗粒进行包衣，再加入矫味剂混合均匀后进行灌装，由此来掩盖药物的苦味以及提高药物的溶出度，但是此方法采用到的辅料较多，且不能更好的提高药物的溶出度。
发明内容
本发明的目的是针对现有技术的不足而提供一种罗红霉素胶囊的制备方法，即可直接服用下去又可根据需要将胶囊拆开将里面的药物冲水服用，利用高分子黏合剂Eudragit E100(甲基丙烯酸丁酯∶甲基丙烯酸二甲氨基乙酯∶甲基丙烯酸甲酯20∶40∶20共聚物)的水分散体代替传统的有机溶剂包衣，获得了溶出度高，稳定性较好的罗红霉素胶囊，节省了原料成本，适于工业化生产，减少对包衣材料和乳化剂的使用，节约生产成本，有利于安全生产和环境保护，能对药物的苦味进行掩盖的同时又能提高药物的溶出度，适用人群范围较广，局限性较小。
为了完成上述目的，本发明采用以下技术方案：
一种罗红霉素胶囊的制备方法，包括如下步骤：
S1：将原料罗红霉素，辅料黄原胶、高分子黏合剂、稀释剂以及抗粘剂分别粉碎过60目筛，备用；
S2：将高分子粘合剂溶解在乙醇溶液中，制备成醇溶液的混悬液，在混悬液中加入抗粘剂使用搅拌机中速持续搅拌，制成待包衣用混悬液，将混悬液过40目筛进行过滤；
S3：将罗红霉素置于流化床制粒机与稀释剂充分混合均匀，调节合适的风量，使罗红霉素原料充分流化，得到混合物；
S4：在流化床内，调节合适的温度，在压缩空气的作用下使混悬液形成雾化液滴，缓慢喷洒在充分混合的混合物表面，进行流化床制粒，得到罗红霉素包衣物，包衣增重的质量控制为2-4％；
S5：将S4中的包衣物与黄原胶混合，干燥，筛选所得颗粒，然后灌装 胶囊。
作为对本发明的进一步改进，包括如下重量份：罗红霉素8-20重量份，黄原胶2-8重量份，高分子黏合剂20-30重量份，稀释剂100-150重量份，抗粘剂25-50重量份。
作为对本发明的进一步改进，包括如下重量份：罗红霉素15重量份，黄原胶4重量份，高分子黏合剂25重量份，稀释剂130重量份，抗粘剂38重量份。
作为对本发明的进一步改进，所述稀释剂为蔗糖、甘露醇、木糖醇和赤藓糖醇中的一种或几种的混合物。
作为对本发明的进一步改进，所述高分子黏合剂为Eudragit E100、II号丙烯酸树脂、III号丙烯酸树脂、IV号丙烯酸树脂、羧甲基纤维素钠中的一种或多种，所述Eudragit E100为甲基丙烯酸丁酯∶甲基丙烯酸二甲氨基乙酯∶甲基丙烯酸甲酯20∶40∶20的共聚物。
作为对本发明的进一步改进，所述高分子黏合剂为Eudragit E100。
作为对本发明的进一步改进，所述抗粘剂为滑石粉、硬脂酸镁或单硬脂酸甘油脂中的一种。
作为对本发明的进一步改进，所述抗粘剂为滑石粉。
作为对本发明的进一步改进，所述流化床制粒机的参数为，风量60m
3/h,进风温度35-50℃，雾化压强1.5bar，物料温度为30-40℃，出风温度55°，喷浆流量10g/min，喷嘴热风温度120°。
与现有技术相比，本发明的有益效果是：
1、本发明通过Eudragit E100(甲基丙烯酸丁酯∶甲基丙烯酸二甲氨基 乙酯∶甲基丙烯酸甲酯20∶40∶20共聚物)作为高分子黏合剂，将此作为包衣液喷射于罗红霉素的表面形成包衣物，打破传统的采用包衣材料和乳化剂的混合进行包衣，节省原料的使用，且采用高分子黏合剂形成的包衣物又可掩盖药物的苦味，由此可减少矫味剂和甜味剂的用量，大大降低了辅料的使用，节约生产成本。
2、本发明所制备的胶囊即可直接服用下去又可根据需要将胶囊拆开将里面的药物冲水服用，利用高分子黏合剂Eudragit E100(甲基丙烯酸丁酯∶甲基丙烯酸二甲氨基乙酯∶甲基丙烯酸甲酯20∶40∶20共聚物)的水分散体代替传统的有机溶剂包衣，获得了溶出度高，稳定性较好的罗红霉素胶囊，节省了原料成本，适于工业化生产，减少对包衣材料和乳化剂的使用，节约生产成本，有利于安全生产和环境保护，能对药物的苦味进行掩盖的同时又能提高药物的溶出度，适用人群范围较广，局限性较小。
3、Eudragit E100(甲基丙烯酸丁酯∶甲基丙烯酸二甲氨基乙酯∶甲基丙烯酸甲酯20∶40∶20共聚物)水分散体是一种粒度0.01～0.1微米的聚合物乳胶粒在水中的分散体，聚合物含量为30％(w/w)，粘度低，易于喷雾包衣操作，成膜过程中，乳胶粒形成堆积层，随水份蒸发，表面张力增大，使胶粒紧密聚集，在最低成膜温度以上环境中形成薄膜，这种膜的抗水渗透性优于用有机溶剂包衣液形成的膜，有机溶剂包衣液中溶剂的蒸发由于溶剂化热，需要消耗比水分散体中水蒸发更多的能量，加之后者固体含量高，所以水分散体包衣的能耗较低，有利于节约生产成本，适于工业化生产。
4、在包衣过程中喷洒在药物表面的包衣液随溶剂蒸发而变粘，包衣液中加入适量抗粘剂可减少粘性，避免颗粒与颗粒之间相互粘连，提高包衣效 果。
为了使本技术领域的人员更好地理解本申请方案，下面对本申请实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
实施例1
一种罗红霉素干混悬剂的制备方法，由如下原辅料制成1000袋：
罗红霉素 15g；
黄原胶 4g；
Eudragit E100(甲基丙烯酸丁酯∶甲基丙烯酸二甲氨基乙酯∶甲基丙烯酸甲酯20∶40∶20共聚物) 20g；
甘露醇 100g；
滑石粉 25g。
制备工艺：
a)：将原料罗红霉素，辅料黄原胶、Eudragit E100、甘露醇以及滑石粉分别粉碎过60目筛，备用；
b)：将Eudragit E100(甲基丙烯酸丁酯∶甲基丙烯酸二甲氨基乙酯∶甲基丙烯酸甲酯20∶40∶20共聚物)溶解在乙醇溶液中，制备成醇溶液的混悬液，在混悬液中加入滑石粉使用搅拌机中速持续搅拌，制成待包衣用混悬液，将混悬液过40目筛进行过滤；
c)：将罗红霉素置于流化床制粒机与甘露醇充分混合均匀，调节风量60m
3/h，进风温度40℃，使罗红霉素原料充分流化，得到混合物；
d)：在流化床内，调节流化床的雾化压强为1.5bar，出风温度为55°，喷浆流量为10g/min，喷嘴热风温度为120°，在压缩空气的作用下使混悬液形成雾化液滴，缓慢喷洒在充分混合的混合物表面，进行流化床制粒，得到罗红霉素包衣物，包衣增重的质量控制为2-4％；
e)：将步骤d中的包衣物与黄原胶混合，干燥，筛选所得颗粒，然后灌装胶囊。
实施例2
一种罗红霉素干混悬剂的制备方法，由如下原辅料制成1000袋：
罗红霉素 15g；
黄原胶 4g；
II号丙烯酸树脂 30g；
蔗糖 150g；
硬脂酸镁 50g。
制备工艺：
a)：将原料罗红霉素，辅料黄原胶、II号丙烯酸树脂、蔗糖以及硬脂酸镁分别粉碎过60目筛，备用；
b)：将II号丙烯酸树脂溶解在乙醇溶液中，制备成醇溶液的混悬液，在混悬液中加入硬脂酸镁使用搅拌机中速持续搅拌，制成待包衣用混悬液，将混悬液过40目筛进行过滤；
c)：将罗红霉素置于流化床制粒机与蔗糖充分混合均匀，调节风量 60m
3/h，进风温度40℃，使罗红霉素原料充分流化，得到混合物；
d)：在流化床内，调节流化床的雾化压强为1.5bar，出风温度为55°，喷浆流量为10g/min，喷嘴热风温度为120°，在压缩空气的作用下使混悬液形成雾化液滴，缓慢喷洒在充分混合的混合物表面，进行流化床制粒，得到罗红霉素包衣物，包衣增重的质量控制为2-4％；
e)：将步骤d中的包衣物与黄原胶混合，干燥，筛选所得颗粒，然后灌装胶囊。
实施例3
一种罗红霉素干混悬剂的制备方法，由如下原辅料制成1000袋：
罗红霉素 15g；
黄原胶 4g；
羧甲基纤维素钠 25g；
木糖醇 120g；
单硬脂酸甘油脂 40g。
制备工艺：
a)：将原料罗红霉素，辅料黄原胶、羧甲基纤维素钠、木糖醇以及单硬脂酸甘油脂分别粉碎过60目筛，备用；
b)：将羧甲基纤维素钠溶解在乙醇溶液中，制备成醇溶液的混悬液，在混悬液中加入单硬脂酸甘油脂使用搅拌机中速持续搅拌，制成待包衣用混悬液，将混悬液过40目筛进行过滤；
c)：将罗红霉素置于流化床制粒机与木糖醇充分混合均匀，调节风量60m
3/h，进风温度40℃，使罗红霉素原料充分流化，得到混合物；
d)：在流化床内，调节流化床的雾化压强为1.5bar，出风温度为55°，喷浆流量为10g/min，喷嘴热风温度为120°，在压缩空气的作用下使混悬液形成雾化液滴，缓慢喷洒在充分混合的混合物表面，进行流化床制粒，得到罗红霉素包衣物，包衣增重的质量控制为2-4％；
e)：将步骤d中的包衣物与黄原胶混合，干燥，筛选所得颗粒，然后灌装胶囊。
实验例
1、苦味测试：
将上述实施例制备得到的罗红霉素胶囊分别拆开胶囊将里面的药物冲水给予60名志愿者试用，让其服用后，记录受试者口感：将罗红霉素分别分散在30℃水15ml中，10min后，每个志愿者依次对各个样品进行评价，***lml样品分散液20s，然后吐出，评价苦味的等级，漱口，再按上述方法评价另一样品。结果见表1。
表1
| 口感 | 实施例1 | 实施例2 | 实施例3 |
| 极苦 | 0 | 0 | 0 |
| 有点苦，可接受 | 35％ | 25％ | 40％ |
| 苦味很淡 | 42％ | 32％ | 26％ |
| 完全不苦 | 0 | 0 | 0 |
从表1结果可以看出，实施例1-3的罗红霉素胶囊内的药物采用水分散体作为包衣液对罗红霉素进行包衣与上市的罗红霉素胶囊内的药物采用有机溶剂作为包衣液进行包衣相比，实施例1-3中的罗红霉素胶囊苦味得到掩盖。
2、溶出度测试：
以900mlpH为1.2的盐酸溶液作为溶出介质，验证罗红霉素胶囊的溶出 度，溶出度试验条件如下：
(1)溶出度测定条件
色谱柱：Alltech C 18(150×4.6mm I.D.)
流动相：乙腈-水(60:40)
检测波长：UV 220nm
流速：2.0ml/min
进样量：20μl
(2)溶出度实验方法
分别取实施例1-3的样品，照溶出度测定法(中国药典2010版二部附录XC第二法)，以900ml pH为1.2的盐酸溶液为溶剂，转速为每分钟100转，依法操作，分别经5、10、15、30、45、60分钟时取溶液适量，滤过，取续滤液作为供试品溶液。另精密称取罗红霉素对照品5mg，置50ml容量瓶中，用乙腈-水(70:30)溶解并稀释至刻度，摇匀，精密量取适量，用水稀释成每1ml中含罗红霉素5μg的溶液，作为对照品溶液，30min后算出各个样品的溶出量，限度为85％，各个样品的溶出量测定数据如下表2所示。
表2
| 样品 | 溶出度(％) |
| 实施例1 | 98.65％ |
| 实施例2 | 96.36％ |
| 实施例3 | 97.21％ |
由表2可知，本发明所述制成的胶囊表现出良好的溶出行为，30min的溶出度均大于90％，说明在该范围内罗红霉素的苦味得到了良好的掩盖，并且其溶出度不受影响。
虽然本发明已利用上述较佳实施例进行说明，但其并非用以限定本发明 的保护范围，任何本领域技术人员在不脱离本发明的精神和范围之内，相对上述实施例进行各种变动与修改仍属于本发明所保护的范围。
Claims (9)
- 一种罗红霉素胶囊的制备方法，其特征在于，包括如下步骤：S1：将原料罗红霉素，辅料黄原胶、高分子黏合剂、稀释剂以及抗粘剂分别粉碎过60目筛，备用；S2：将高分子粘合剂溶解在乙醇溶液中，制备成醇溶液的混悬液，在混悬液中加入抗粘剂使用搅拌机中速持续搅拌，制成待包衣用混悬液，将混悬液过40目筛进行过滤；S3：将罗红霉素置于流化床制粒机与稀释剂充分混合均匀，调节合适的风量，使罗红霉素原料充分流化，得到混合物；S4：在流化床内，调节合适的温度，在压缩空气的作用下使混悬液形成雾化液滴，缓慢喷洒在充分混合的混合物表面，进行流化床制粒，得到罗红霉素包衣物，包衣增重的质量控制为2-4％；S5：将S4中的包衣物与黄原胶混合，干燥，筛选所得颗粒，然后灌装胶囊。
- 根据权利要求1所述的一种罗红霉素胶囊的制备方法，其特征在于，包括如下重量份：罗红霉素8-20重量份，黄原胶2-8重量份，高分子黏合剂20-30重量份，稀释剂100-150重量份，抗粘剂25-50重量份。
- 根据权利要求2所述的一种罗红霉素胶囊的制备方法，其特征在于，包括如下重量份：罗红霉素15重量份，黄原胶4重量份，高分子黏合剂25重量份，稀释剂130重量份，抗粘剂38重量份。
- 根据权利要求1、2或3所述的一种罗红霉素胶囊的制备方法，其特征在于，所述稀释剂为蔗糖、甘露醇、木糖醇和赤藓糖醇中的一种或几种的混合物。
- 根据权利要求1、2或3所述的一种罗红霉素胶囊的制备方法，其特征在于，所述高分子黏合剂为Eudragit E100、II号丙烯酸树脂、III号丙烯酸树脂、IV号丙烯酸树脂、羧甲基纤维素钠中的一种或多种，所述EudragitE100为甲基丙烯酸丁酯∶甲基丙烯酸二甲氨基乙酯∶甲基丙烯酸甲酯20∶40∶20的共聚物。
- 根据权利要求5所述的一种罗红霉素胶囊的制备方法，其特征在于，所述高分子黏合剂为Eudragit E100。
- 根据权利要求1、2或3所述的一种罗红霉素胶囊的制备方法，其特征在于，所述抗粘剂为滑石粉、硬脂酸镁或单硬脂酸甘油脂中的一种。
- 根据权利要求7所述的一种罗红霉素胶囊的制备方法，其特征在于，所述抗粘剂为滑石粉。
- 根据权利要求1所述的一种罗红霉素胶囊的制备方法，其特征在于，所述流化床制粒机的参数为，风量60m 3/h,进风温度35-50℃，雾化压强1.5bar，物料温度为30-40℃，出风温度55°，喷浆流量10g/min，喷嘴热风温度120°。
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1744881A (zh) * | 2003-04-02 | 2006-03-08 | 普利瓦研究与发展有限公司 | 苦味减轻了的药物组合物 |
| CN1813683A (zh) * | 2005-12-07 | 2006-08-09 | 范敏华 | 一种阿奇霉素的干混悬剂及其制备方法 |
| CN102266309A (zh) * | 2011-07-12 | 2011-12-07 | 江苏黄河药业股份有限公司 | 一种新型罗红霉素胶囊及其制备方法 |
| CN105560210A (zh) * | 2015-11-26 | 2016-05-11 | 陕西高新能源发展有限公司 | 罗红霉素干混悬剂及其制备方法 |
| CN105832700A (zh) * | 2016-03-24 | 2016-08-10 | 河南中帅医药科技股份有限公司 | 一种大环内酯类药物的细颗粒及其制备方法 |
| CN106619532A (zh) * | 2016-11-16 | 2017-05-10 | 山东裕欣药业有限公司 | 一种罗红霉素盐酸氨溴索干混悬剂及其制备方法 |
| CN113181133A (zh) * | 2021-04-25 | 2021-07-30 | 海南通用三洋药业有限公司 | 一种罗红霉素胶囊的制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPN969796A0 (en) * | 1996-05-07 | 1996-05-30 | F.H. Faulding & Co. Limited | Taste masked liquid suspensions |
| KR20040011087A (ko) * | 2002-07-27 | 2004-02-05 | 주식회사 씨티씨바이오 | 불쾌한 맛과 향을 차폐할 수 있는 록시스로마이신 과립의제조방법 |
| CN1526449A (zh) * | 2003-03-06 | 2004-09-08 | 上海现代浦东药厂有限公司 | 改善及抑制药物苦味的方法 |
| CN1537539A (zh) * | 2003-04-14 | 2004-10-20 | 上海丽珠制药有限公司 | 具有包衣的罗红霉素微囊以及采用流化床的制备方法 |
| CN101869549A (zh) * | 2009-04-21 | 2010-10-27 | 北京利乐生制药科技有限公司 | 一种以罗红霉素为主要成分的口服缓释干混悬剂 |
| CN106727347A (zh) * | 2016-12-13 | 2017-05-31 | 浙江中同科技有限公司 | 一种掩味罗红霉素干混悬剂及其制备方法 |
| CN111388444B (zh) * | 2020-03-18 | 2022-05-20 | 北京鑫开元医药科技有限公司 | 一种罗红霉素颗粒及其制备方法 |
-
2021
- 2021-04-25 CN CN202110447546.1A patent/CN113181133A/zh active Pending
- 2021-05-12 WO PCT/CN2021/093192 patent/WO2022227116A1/zh active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1744881A (zh) * | 2003-04-02 | 2006-03-08 | 普利瓦研究与发展有限公司 | 苦味减轻了的药物组合物 |
| CN1813683A (zh) * | 2005-12-07 | 2006-08-09 | 范敏华 | 一种阿奇霉素的干混悬剂及其制备方法 |
| CN102266309A (zh) * | 2011-07-12 | 2011-12-07 | 江苏黄河药业股份有限公司 | 一种新型罗红霉素胶囊及其制备方法 |
| CN105560210A (zh) * | 2015-11-26 | 2016-05-11 | 陕西高新能源发展有限公司 | 罗红霉素干混悬剂及其制备方法 |
| CN105832700A (zh) * | 2016-03-24 | 2016-08-10 | 河南中帅医药科技股份有限公司 | 一种大环内酯类药物的细颗粒及其制备方法 |
| CN106619532A (zh) * | 2016-11-16 | 2017-05-10 | 山东裕欣药业有限公司 | 一种罗红霉素盐酸氨溴索干混悬剂及其制备方法 |
| CN113181133A (zh) * | 2021-04-25 | 2021-07-30 | 海南通用三洋药业有限公司 | 一种罗红霉素胶囊的制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| ZHOU QINGHUA , TAN HUAJIAN , WU HONGYAN: "Prescription and technology of dry suspension prepared by roxithromycin coating and taste masking", JOURNAL OF NORTH PHARMACY, vol. 12, no. 3, 1 March 2015 (2015-03-01), pages 107 - 108, XP055982122, ISSN: 1672-8351 * |
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