CN1939267A - Oral preparation containing amoxicillin clatrenoin and its making method - Google Patents
Oral preparation containing amoxicillin clatrenoin and its making method Download PDFInfo
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- CN1939267A CN1939267A CN 200610152620 CN200610152620A CN1939267A CN 1939267 A CN1939267 A CN 1939267A CN 200610152620 CN200610152620 CN 200610152620 CN 200610152620 A CN200610152620 A CN 200610152620A CN 1939267 A CN1939267 A CN 1939267A
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- amoxicillin
- clavulanic acid
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Abstract
An orally absorbed medicine in the form of buccal lozenge, sweets, or dripping pill dissolved by saliva features that it contains amoxicillin and clavulanic acid. Its preparing process is also disclosed.
Description
[technical field] the present invention relates to a kind of medicine and preparation method thereof, particularly contains buccal lozenge of amoxicillin and clavulanic acid and preparation method thereof.
[background technology]
Pharyngitis is the modal disease of puzzlement modern life, is pharyngeal mucous membrane, submucous tissue and adenoid diffuse inflammation, often is the part of upper respiratory tract infection.Be divided into acute and chronic two kinds clinically.Acute pharyngitis is many in autumn and winter and morbidity at the end of winter and the beginning of spring.Pathological changes ordinary wave and whole pharyngeal cavity also can limit to a place.Can cause by virus, antibacterial and physical chemical factor and high temperature, dust, fumagine, irritative gas etc.Bacterial infection is based on gram-positive coccis such as streptococcus, staphylococcus and Diplococcus pneumoniaes.Wherein serious with A group group B streptococcus causer, antibacterial or toxin enter blood, can cause the purulent lesion of organ at a distance, are called acute septic pharyngitis.Treat with oral or injection antibiotics control infection.
The chronic pharyngitis course of disease is very long, and the symptom stubbornness is often by due to the local infection or general pathological changes secondary, with chronic pathological changes repeatedly acute attack be its characteristics, in many cases, acute attack is to be caused by bacterial infection, therefore, suitable antibacterial therapy helps to control acute symptom.
Acute tonsillitis is a kind of non-specific acute inflammation of very common palatine tonsil, often with to a certain degree pharyngeal mucous membrane and swallow adenoid acute inflammation.Main pathogenic bacterium are streptococcus, staphylococcus, Diplococcus pneumoniae.Adenovirus also can cause primary disease.Antibacterial and virus mixed infection are quite a few to be seen.Antibacterial may be extraneous the intrusion, also may be the antibacterial that is hidden in the tonsillar crypts, when Abwehrkraft des Koepers because of cold, humidity, overworked, have a delicate constitution, tobacco and wine are excessive, when factors such as harmful gas stimulation reduce suddenly, due to bacterial reproduction is strengthened.Acute tonsillitis is acute attack repeatedly on chronic tonsil basis often.Clinical manifestation aversion to cold, hyperpyrexia, pharyngalgia, aggravation etc. when swallowing can the concurrent rheumatic fever relevant with hemolytic streptococcal infection, multiple general diseases such as acute glome-rulonephritis, myocarditis, arthritis.Treatment adopts pain relieving to bring down a fever, oral or injection antibiotics control infection.
The amoxicillin is the semi-synthetic penicillium sp rope of a kind of wide spectrum, the stronger bacteria cell wall ability that penetrates is arranged, by suppressing the glycosidase of antibacterial, make the bacteria cell wall biosynthesis block, formation spheroplast breaks and dissolves death rapidly, be the active drug that infects due to a kind of clinical practice wide range of therapeutic gram negative bacteria and the gram positive bacteria, but the independent use in amoxicillin mainly is applicable to the infection due to the sensitive organism that does not produce beta lactamase.Continually develop and be widely used in clinical along with antibiotic, caused drug-resistance of bacteria, antibacterial is day by day increased the drug resistance of common antibiotics.Antibacterial produces drug resistance through number of ways to antibiotic, wherein to produce beta lactamase.Use beta lactamase restrainer can improve the antibiotic antibacterial activity of some beta-lactam class greatly, and enlarge antimicrobial spectrum.The beta lactamase restrainer that is most widely used at present is a clavulanic acid.Clavulanic acid claims clavulanic acid again, is bacteriogenic natural lactamase restrainer, contains the beta-lactam ring in the structure, and antibacterial action is very weak, presses down the enzyme effect but have strong effect wide-spectrum.It with enzyme firm combining takes place makes enzyme deactivation, and the elimination with inhibitor does not bring back to life.The no clinical value of simple use, normal and other beta-lactam class antibiotic share, to strengthen antibacterial action.The beta lactamase that the beta lactamase that clavulanic acid produces staphylococcus aureus, gram negative bacilli produce has obvious inhibitory action.Amoxicillin/clavulanate has been developed into tablet, capsule, injection etc., all adopts whole body administrations such as oral or injection.Be easy to cause the local pain reaction when using inconvenience, administration in view of injection.Oral absorption such as tablet and capsule is slower, and entering behind the blood distributes by whole body dilutes medicine in blood, make medicine lower at the blood drug level of diseased region, and it is also longer to reach time of effective blood drug concentration at diseased region, influences its effective antibacterial efficacy.Therefore, the development buccal lozenge, by the oral cavity buccal, directly act on diseased region with high concentration medicine, be used for pharyngitis, pharyngoamygdalitis and oral cavity infection treatment of diseases, can overcome above-mentioned shortcoming, can kill oral cavity, the various pathogenic microorganism in throat rapidly, for effective treatment of throat oral cavity infection disease provides strong treatment means.
[summary of the invention]
The purpose of this invention is to provide a kind of is buccal lozenge of ingredient and preparation method thereof with amoxicillin and clavulanic acid, and the medicine through port is contained in the intraoral saliva and dissolves, and enters around the oral cavity, pharyngeal and pharyngeal tonsil position, brings into play its antibacterial action.
For achieving the above object, the present invention has adopted following technical scheme.
The buccal lozenge that contains amoxicillin and clavulanic acid of the present invention is meant by ingredient that contains amoxicillin and clavulanic acid and substrate composed preparation, wherein the weight ratio of amoxicillin and Clavulanate is n: 1, n is the number of 2-14, preferred 2: 1,4: 1,6: 1,7: 1,8: 1,10: 1,12: 1 and 14: 1, medicine: substrate=1: 1-1: 30, through port intracavity and sublingual administration administration are used for the treatment of pharyngitis, pharyngoamygdalitis and oral cavity infection clinically.
Wherein, selected amoxicillin is chemical compound and its esters (as sodium salt, potassium salt, hydrochlorate, sulfate, hydrobromate, tartrate, the fumarate etc.) derivant with following feature.
Chinese: amoxicillin
English by name: Amoxicillin
Formal name used at school is: 2S, and 5R, 6R)-3, the 3-dimethyl-6-[(R)-(-)-2-amino-2-(4-hydroxy phenyl) acetylamino]-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-formic acid trihydrate
Molecular formula: C
16H
19N
3O
5S3H
2O
Molecular weight: 419.46
Amoxicillin salt derivative commonly used is the amoxicillin sodium salt
Wherein, selected clavulanic acid is chemical compound and its esters (as sodium salt, potassium salt, hydrochlorate, sulfate, hydrobromate, tartrate, the fumarate etc.) derivant with following feature: English Clavulanate by name, molecular formula: C
8H
8KNO
5, molecular weight: 237.25, chemical structural formula is:
Clavulanic acid salt derivative commonly used is a clavulanic acid potassium salt.
Wherein said substrate is the preparation adjuvant that is grouped into by one or more one-tenth, comprising:
1, diluent (filler): for example Icing Sugar, gelatin, glycerol, arabic gum, starch, dextrin, lactose, glucose, mannitol, calcium sulfate, calcium hydrogen phosphate, tricalcium phosphate, gelatinized corn starch, syrup, maltose, gelatine size, cellulose, Kaolin, sodium chloride, modified starch (Sta-RX1500), microcrystalline Cellulose etc., wherein Icing Sugar has sucrose, maltose, dextrinose, dextrinose oligosaccharide, panose, cottonseed sugar, stachyose, oligofructose, fructose, inulin, protein sugar, stevioside, xylitol, maltose alcohol, sorbitol;
2, binding agent: for example water, ethanol, starch, gelatin, sucrose, glucose, dextran, syrup, lactose, arabic gum, sodium alginate, gelatine size, polyvinylpyrrolidone, Polyethylene Glycol, methylcellulose, carboxymethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, maltose, sucrose dextrin copolymer;
3, disintegrating agent: for example starch (corn and potato starch), cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, pectin, carboxymethyl cellulose, microcrystalline Cellulose, tween 80, sodium laurylsulfate, stearyl alcohol sodium sulfonate, kaolin.
4, lubricant: for example stearic acid, calcium stearate, magnesium stearate, zinc stearate, hydrogenated vegetable oil, polyoxyethylene monostearate, light mineral oil, liquid paraffin, boric acid, sodium chloride, sodium benzoate, sodium acetate, enuatrol, sodium laurylsulfate (magnesium), single Laurel sucrose acid ester, adipic acid, fumaric acid, three triacetins, Polyethylene Glycol
1500～20000
5, fluidizer: for example starch, purified talc, differential silica gel, pyrolytic silicon dioxide, hydrated sodium aluminosilicate.
6, slow releasing agent: for example hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer 934 P, carbomer 971P, carbomer 974P, stearic acid, hexadecanol, octadecanol, ethyl cellulose, zein etc.
7, other: conventional coloring agent, correctives, spice, as aspartame etc.
Described preparation type includes but not limited to buccal tablet, drop pill, confection, capsule, tablet, injectable powder.
The present invention relates to contain the tablet of following composition:
Described tablet is made up of ingredient that includes amoxicillin and clavulanic acid and substrate, and wherein said substrate contains following material (accounting for the percentage by weight of substrate total amount): diluent 1-100%; Binding agent 0-30%; Disintegrating agent 0-20%; Lubricant 0-20%; Fluidizer 0-20%; Slow releasing agent 0-10% and conventional coloring agent, correctives, spice.
The present invention relates to contain the capsule of following composition:
Described capsule is made up of ingredient that includes amoxicillin and clavulanic acid and substrate, and wherein said substrate contains following material (accounting for the percentage by weight of substrate total amount): diluent 1-100%; Binding agent 0-30%; Disintegrating agent 0-20%; Lubricant 0-20%; Fluidizer 0-20%; Slow releasing agent 0-10% and conventional coloring agent, correctives, spice.
The present invention relates to contain the drop pill of following composition:
Described drop pill is made up of ingredient that includes amoxicillin and clavulanic acid and substrate, adopt water-bath, oil bath or other mode of heating, mixed material is heated to fusion, stir, insert on the drop pill machine with suitable speed, splash in 40 →-15 ℃ the condensing agent liquid paraffin, methyl-silicone oil, vegetable oil any one or a few, drying forms, and its mesostroma is by containing Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more one-tenth in polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers and the medicinal slow release agent are grouped into.
The present invention relates to contain the buccal tablet of following composition:
Described buccal tablet is made up of ingredient that includes amoxicillin and clavulanic acid and substrate, and wherein said substrate contains following material (accounting for the percentage by weight of substrate total amount): diluent 1-100%; Binding agent 0-30%; Disintegrating agent 0-20%; Lubricant 0-20%; Fluidizer 0-20%; Slow releasing agent 0-10% and conventional coloring agent, correctives, spice.
The present invention relates to contain the confection of following composition:
Described confection is made up of ingredient that includes amoxicillin and clavulanic acid and substrate, and wherein said substrate contains following material (accounting for the percentage by weight of substrate total amount): diluent 1-100%; Binding agent 0-20%; Disintegrating agent 0-10%; Lubricant 0-10%; Fluidizer 0-10%; Slow releasing agent 0-10% and conventional coloring agent, correctives, spice.
Preparation method of the present invention comprises following order and step, but following be not limitation of the invention:
1. the preparation method of buccal tablet: proportionally amoxicillin and clavulanic acid are mixed with substrate; When described substrate was Icing Sugar, described buccal tablet contained but is not limited to one or more composition in sucrose, maltose, dextrinose, dextrinose oligosaccharide, panose, cottonseed sugar, stachyose, oligofructose, glucose, fructose, lactose, inulin, protein sugar, stevioside, xylitol, maltose alcohol, sorbitol, gelatinized corn starch, syrup, the maltose etc.; When described substrate was solvent, described buccal tablet contained but is not limited to Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers one or more composition.
(1) takes by weighing an amount of Icing Sugar or other substrate, add water or binding agent, make suitable soft material, add the ingredient that contains amoxicillin and clavulanic acid, stir, cut apart, shaping, drying.
(2) take by weighing an amount of Icing Sugar or other substrate, add the ingredient that contains amoxicillin and clavulanic acid, add water or binding agent, stir, granulate, drying is shaped on tablet machine.
(3) take by weighing an amount of Icing Sugar or other substrate, add the ingredient that contains amoxicillin and clavulanic acid,,, on tablet machine, be shaped then through cooled and solidified through being heated as the miscible or miscible state of semi-molten of fusion.
(4) take by weighing an amount of Icing Sugar or other substrate,, be cooled to 70-100 ℃, add the ingredient that contains amoxicillin and clavulanic acid, stir, on tablet machine, be shaped through being heated as the miscible or miscible state of semi-molten of fusion.
2. the preparation of drop pill: proportionally amoxicillin and clavulanic acid are mixed with substrate; Substrate is by containing Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more one-tenth in polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers are grouped into.Adopt water-bath, oil bath or other mode of heating, mixed material is heated to fusion, stir, insert on the drop pill machine, splash in 40 →-15 ℃ the condensing agent with suitable speed.Condensing agent can be any one or a few in liquid paraffin, methyl-silicone oil, the vegetable oil.
3. the preparation of confection: proportionally amoxicillin and clavulanic acid are mixed with substrate; Matrix filler is to be grouped into by one or more the one-tenth that contains in sucrose, maltose, dextrinose, dextrinose oligosaccharide, panose, cottonseed sugar, stachyose, oligofructose, glucose, fructose, lactose, inulin, protein sugar, stevioside, xylitol, maltose alcohol, sorbitol, gelatinized corn starch, syrup, the maltose etc.
Take by weighing an amount of Icing Sugar or other substrate heat fused, be cooled to uniform temperature then after, add the ingredient contain amoxicillin and clavulanic acid, stir, make into the plasticity magma, cut apart extrusion molding;
4. capsular preparation: proportionally amoxicillin and clavulanic acid are mixed with substrate; Substrate is by containing Icing Sugar, gelatin, glycerol, arabic gum, starch, dextrin, lactose, glucose, mannitol, calcium sulfate, calcium hydrogen phosphate, tricalcium phosphate, gelatinized corn starch, syrup, maltose, gelatine size, polyvinylpyrrolidone, Polyethylene Glycol, methylcellulose, carboxymethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, sucrose dextrin copolymer, Polyethylene Glycol
1500～20000, among stearic acid, sodium stearate, calcium stearate, sodium chloride, fumaric acid, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyoxyethylene stearate 40 esters, polyethers, carboxymethyl starch sodium, silica sol, succinic acid, xanthan gum, aspartame, mannitol, silica gel, silicon dioxide, saccharin sodium, carbomer 934 P, carbomer 971P and carbomer 974P etc. one or more become to be grouped into
Take by weighing an amount of substrate, add the ingredient that contains amoxicillin and clavulanic acid, stir, granulate capsule charge;
5. the preparation of tablet: proportionally amoxicillin and clavulanic acid are mixed with substrate; Substrate is by containing Icing Sugar, gelatin, glycerol, arabic gum, starch, dextrin, lactose, glucose, mannitol, calcium sulfate, calcium hydrogen phosphate, tricalcium phosphate, gelatinized corn starch, syrup, maltose, gelatine size, polyvinylpyrrolidone, Polyethylene Glycol, methylcellulose, carboxymethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, sucrose dextrin copolymer, Polyethylene Glycol
1500～20000, among stearic acid, sodium stearate, calcium stearate, sodium chloride, fumaric acid, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyoxyethylene stearate 40 esters, polyethers, carboxymethyl starch sodium, silica sol, succinic acid, xanthan gum, aspartame, mannitol, silica gel, silicon dioxide, saccharin sodium, carbomer 934 P, carbomer 971P and carbomer 974P etc. one or more become to be grouped into
Take by weighing an amount of substrate, add the ingredient that contains amoxicillin and clavulanic acid, stir, granulate, tabletting is shaped on tablet machine;
Amoxicillin of the present invention is compared with existing general formulation with the clavulanic acid buccal lozenge has following benefit:
1) amoxicillin and the clavulanic acid concentration at raising position, sick limit improve its antibacterial ability.Medicine dissolves in the saliva in the oral cavity, enters around the oral cavity, pharyngeal and pharyngeal tonsil position.These medicines do not pass through hemodilution, form high local concentrations, strengthen antibacterial ability.
2) rapid-action.Medicine is behind dissolved in oral cavity, and effect and pathological tissues have saved the time limit that absorbs distribution immediately.
3) convenient drug administration.To amoxicillin and the clavulanic acid of need,, directly act on position, disease limit then by sucking the messenger drug thing at dissolved in oral cavity through the parenteral route administration.
[specific implementation method]
By following concrete embodiment, can further understand the present invention, but following example not a limitation of the invention.
Embodiment 1-amoxicillin and clavulanate confection
Prescription: Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) 37.5g, sucrose 853g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g, 1000 of amount of formulation.
Method: preparation Amoxicillin Sodium 87.5g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g mixture grind, and cross 20 purpose sieves.Get sucrose 853 grams, be heated to 140 ℃ of fusings, be cooled to 85 ℃, add the mixture after sieving, stirred 10 minutes fast, be cooled to and solidify, granulate, grind, cross 20 purpose sieves, add the Amoxicillin Sodium after sieving: clavulanate potassium (2: 1) mixture 37.5g, stirred 10 minutes fast, place extrusion molding on the product shaping machine, every buccal tablet weighs 1 gram.Measure the disintegration of amoxicillin and clavulanate confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 4-8 minute disintegration, and fully the dissolution during disintegrate is 93%-95%.
Embodiment 2-low sugar amoxicillin and clavulanate confection (1)
Prescription: Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) 37.5g, sucrose 203g, oligofructose 300g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g, 1000 of amount of formulation.
Method: preparation Amoxicillin Sodium 87.5g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g mixture grind, and cross 20 purpose sieves.Get sucrose 203g, oligofructose 300g, xylitol 300g, inulin 50g, mix, be heated to 140 ℃ of fusings, be cooled to 85 ℃, add the mixture after sieving, stirred fast 10 minutes, be cooled to and solidify, granulate, grind, cross 20 purpose sieves, add the Amoxicillin Sodium after sieving: clavulanate potassium (2: 1) mixture 37.5g, place extrusion molding on the product shaping machine, every buccal tablet weighs 1 gram.Measure the disintegration of amoxicillin and clavulanate confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 5-8 minute disintegration, and fully the dissolution during disintegrate is 93%-96%.
Embodiment 3-low sugar amoxicillin and clavulanate buccal tablet (1)
Prescription: Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) 37.5g, gelatin 240g, glycerol 60g, water 60g, oligofructose 133g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, magnesium stearate 10g, carbomer 934 P 2g, 1000 of amount of formulation.
Method: preparation gelatin 240g, glycerol 60g, water 60g mixed-matrix, dry, add Amoxicillin Sodium 87.5g, Amoxicillin Sodium again: clavulanate potassium (2: 1) 37.5g, oligofructose 133g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P2g mixture, grind, cross 20 purpose sieves, granulate with the second alcohol and water, 60 ℃ of dryings, add 10 gram magnesium stearate then, mixing places extrusion molding on the tablet machine, and every buccal tablet weighs 1 gram.Measure the disintegration of amoxicillin and clavulanate buccal tablet in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 13-17 minute disintegration, and fully the dissolution during disintegrate is 96%-99%.
Embodiment 4-amoxicillin and clavulanate buccal tablet
Prescription: Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) 37.5g, hypromellose 100 grams, Polyethylene Glycol
6000775 grams, aspartame 0.1 gram, 1000 of amount of formulation.
Method: preparation hypromellose 100 grams, Polyethylene Glycol
6000775 grams, aspartame 0.1 gram mixed-matrix, heat fused, be cooled to 80 ℃, add Amoxicillin Sodium 87.5g, stirring and evenly mixing, room temperature is cooled to solidifies, granulate, cross 20 purpose sieves, add the Amoxicillin Sodium after sieving: clavulanate potassium (2: 1) mixture 37.5g, place extrusion molding on the tablet machine, every buccal tablet weighs 1 gram.Measure the disintegration of amoxicillin and clavulanate sodium lozenge in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 26-30 minute disintegration, and fully the dissolution during disintegrate is 95%-99%.
Embodiment 5-low sugar amoxicillin and clavulanate confection (2)
Prescription: Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) 37.5g, sucrose 203g, oligofructose 300g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g, 1000 of amount of formulation.
Method: preparation Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) 37.5g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g mixture grind, and cross 20 purpose sieves.Get sucrose 203g, oligofructose 300g, xylitol 300g, inulin 50g, mix, be heated to 140 ℃ of fusings, be cooled to and solidify, granulate, grind, cross 20 purpose sieves, add the mixture after sieving, stirred 10 minutes fast, place extrusion molding on the product shaping machine, every heavy 1 gram.Measure the disintegration of amoxicillin and clavulanate confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 7-9 minute disintegration, and fully the dissolution during disintegrate is 91%-93%.
The preparation of embodiment 6-amoxicillin and clavulanate buccal drop pills
Method: taking polyethylene glycol 4,000 8.3 restrains respectively, polyethylene glycol 6000 7 grams, polyoxyethylene stearate 40 esters 1 gram, carbomer 2 grams, betacyclodextrin 1 gram, poloxamer 0.5 gram, carboxymethyl starch sodium 0.5 gram, stearic acid 0.1 gram, sodium stearate 0.1 gram, glycerin gelatine 0.1 gram, glyceryl monostearate 0.1 gram, Lac 0.1 gram, polyoxyethylene monostearate 0.1 gram, polyethers 0.1 gram, mix homogeneously, add amoxicillin and clavulanate raw material powder 30 grams again, fully mix, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, adopt homemade special drilling pill machine, regulate its water dropper temperature and make it remain on 85 ℃ (error＜2%); With the methyl-silicone oil is condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 20 →-5 ℃ (error＜5%), the system of dripping, wait to take out behind the type of being shrunk to, remove the surface condensation agent, dry, make the drop pill that contains amoxicillin and clavulanate 30mg/ grain, carry out then rounding rate (%), dissolve scattered time limit (minute), the mensuration of the ball method of double differences different (%) and hardness, the rounding rate is 78% as a result, and dissolve scattered time limit 6-8 minute, the ball method of double differences was different from 10%, hardness is qualified, and fully the dissolution during disintegrate is 90%-99%.
Embodiment 7-low sugar amoxicillin and clavulanate buccal tablet (2)
Prescription: Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) 37.5g, gelatin 240g, glycerol 40g, water 60g, oligofructose 180g, xylitol 192g, inulin 50g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, magnesium stearate 10g, hypromellose 143 grams, 1000 of amount of formulation.
Method: preparation gelatin 240g, glycerol 40g, water 60g mixed-matrix, dry, add Amoxicillin Sodium 87.5g, Amoxicillin Sodium again: clavulanate potassium (2: 1) 37.5g, oligofructose 180g, xylitol 192g, inulin 50g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, hypromellose 143 gram mixture, grind, cross 20 purpose sieves, granulate with the second alcohol and water, 60 ℃ of dryings, add 10 gram magnesium stearate then, mixing places extrusion molding on the tablet machine, and every buccal tablet weighs 1 gram.Measure the disintegration of amoxicillin and clavulanate buccal tablet in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 24-28 minute disintegration, and fully the dissolution during disintegrate is 93%-98%.
Embodiment 8-low sugar amoxicillin and clavulanate confection (3)
Prescription: Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) 37.5g, sucrose 83g, oligofructose 300g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, hypromellose 252 grams, 1000 of amount of formulation.
Method: preparation Amoxicillin Sodium 87.5g, Amoxicillin Sodium: clavulanate potassium (2: 1) mixture 37.5g, citric acid 20g, food pigment-40 0.1g, mannitol 20g, hypromellose 252 gram mixture grind, and cross 20 purpose sieves.Get sucrose 83g, oligofructose 170g, xylitol 300g, inulin 5g, mix, be heated to 140 ℃ of fusings, be cooled to room temperature and solidify, granulation, grinding, 20 orders sieve, and add the mixture after sieving, stirred 10 minutes fast, place extrusion molding on the product shaping machine, every buccal tablet weighs 2 grams.Measure the disintegration of amoxicillin and clavulanate confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 39-45 minute disintegration, and fully the dissolution during disintegrate is 90%-93%.
Claims (10)
1. one kind is the buccal lozenge of main ingredient with amoxicillin and clavulanic acid, form by ingredient that includes amoxicillin and clavulanic acid and substrate, wherein the weight ratio of amoxicillin and Clavulanate is n: 1, and n is the number of 2-14, medicine: substrate=1: 1-1: 30.
2. the buccal lozenge of amoxicillin according to claim 1 and clavulanic acid is characterized in that: described buccal lozenge is used for through port intracavity and sublingual administration administration.
3. the buccal lozenge of amoxicillin according to claim 1 and clavulanic acid is characterized in that: described buccal lozenge is clinical to be used for but to be not limited to treat pharyngitis, pharyngoamygdalitis and oral cavity infection.
4. the buccal lozenge of amoxicillin according to claim 1 and clavulanic acid, it is characterized in that: described clavulanic acid is clavulanic acid and salt derivative thereof, the amoxicillin is Utimox and salt derivative thereof, and wherein the toatl proportion between amoxicillin and the Clavulanate is preferred 2: 1,4: 1,6: 1,7: 1,8: 1,10: 1,12: 1 and 14: 1.
5. the buccal lozenge of amoxicillin according to claim 1 and clavulanic acid is characterized in that: described preparation type includes but not limited to buccal tablet, drop pill, confection, capsule, tablet.
6. the described a kind of preparation method that contains the buccal tablet of amoxicillin and clavulanic acid of claim 5, it is characterized in that: described buccal tablet is through being heated as the miscible or miscible state of semi-molten of fusion by the ingredient that contains amoxicillin and clavulanic acid and substrate, then through cooled and solidified, and then make described buccal tablet, its mesostroma is by containing Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers one or more one-tenth be grouped into.
7. the described a kind of preparation method that contains the buccal tablet of amoxicillin and clavulanic acid of claim 5, it is characterized in that: described buccal tablet is by ingredient that contains amoxicillin and clavulanic acid and substrate mix homogeneously, granulate, dry, on tablet machine, be shaped, and then make described buccal tablet.
8. a kind of preparation method of drop pill according to claim 5, it is characterized in that: proportionally amoxicillin and clavulanic acid are mixed with substrate, adopt water-bath, oil bath or other mode of heating, mixed material is heated to fusion, stir, insert on the drop pill machine with suitable speed, splash in 40 →-15 ℃ the condensing agent and be shaped, its mesostroma is by containing Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more one-tenth in polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers are grouped into.
9. the described a kind of preparation method that contains the confection of amoxicillin and clavulanic acid of claim 5, it is characterized in that: described confection be earlier with substrate through being heated as the miscible state of fusion, then through being cooled to semi-solid, add the ingredient that contains amoxicillin and clavulanic acid then, stirring and evenly mixing, make into the plasticity magma, cut apart, extrusion molding.
10. according to claim 6,7,8 and 9 described preparation methoies, it is characterized in that: described substrate also can add one or more medicinal slow releasing agent and conventional coloring agent, correctives, spice.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610152620 CN1939267A (en) | 2005-09-26 | 2006-09-25 | Oral preparation containing amoxicillin clatrenoin and its making method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510104990.4 | 2005-09-26 | ||
| CN200510104990 | 2005-09-26 | ||
| CN 200610152620 CN1939267A (en) | 2005-09-26 | 2006-09-25 | Oral preparation containing amoxicillin clatrenoin and its making method |
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| Publication Number | Publication Date |
|---|---|
| CN1939267A true CN1939267A (en) | 2007-04-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200610152620 Pending CN1939267A (en) | 2005-09-26 | 2006-09-25 | Oral preparation containing amoxicillin clatrenoin and its making method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110051637A (en) * | 2019-05-21 | 2019-07-26 | 葵花药业集团北京药物研究院有限公司 | Amoxicillin and clavulanate potassium preparation and preparation method thereof |
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2006
- 2006-09-25 CN CN 200610152620 patent/CN1939267A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110051637A (en) * | 2019-05-21 | 2019-07-26 | 葵花药业集团北京药物研究院有限公司 | Amoxicillin and clavulanate potassium preparation and preparation method thereof |
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