CN1151791C - Sustained-release composition containing cefaclor - Google Patents

Sustained-release composition containing cefaclor Download PDF

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CN1151791C
CN1151791C CNB998068233A CN99806823A CN1151791C CN 1151791 C CN1151791 C CN 1151791C CN B998068233 A CNB998068233 A CN B998068233A CN 99806823 A CN99806823 A CN 99806823A CN 1151791 C CN1151791 C CN 1151791C
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cefaclor
mixture
weight
compositions
bicarbonate
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CN1303291A (en
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金贤洙
朴映准
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Yuhan Corp
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0065Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0002Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007Effervescent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2072Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

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Abstract

A composition comprising 30 to 90% by weight of cefaclor, 5 to 60% by weight of a hydroswelling polymer and 1 and to 10% by weight of salt based on the total weight of the composition releases cefaclor in the gastric fluid in a steady sustained manner over a period over 20 hours.

Description

The slow releasing composition that comprises cefaclor
Invention field
The present invention relates to comprise the new sustained release compositions of cefaclor.
Description of the Prior Art
Cefaclor is a kind of oral cephalosporin class antibiotic, and it is stable under pH 4.5 or lower sour environment, and mainly is to absorb at upper digestive tract.Common cefaclor preparation is administered three times every day at least, this be because the half-life of cefaclor in serum shorter relatively, promptly, be lower than 1 hour.Therefore, carry out many trials and developed the new formulation that can in long-time, continue to discharge cefaclor.
The 4th, 713, No. 247 U.S. Patent Publications a kind of durative action preparation of cefaclor, it is by the Shionogi ﹠amp of Japan; Co., Ltd. is with L-KEFRAL For trade name is sold.Above-mentioned preparation is a capsule formulation, it comprises the mixture of rapid release component and slow release component, and the ratio of these two kinds of components is about 4: 6, and wherein the rapid release component discharges cefaclor in gastric juice, and the slow release component is dissolved in intestinal, thus can administration every day 2 times.
The 4th, 968, No. 508 United States Patent (USP) has been described a kind of preparation that is used for sustained-release administration, and it comprises cefaclor, hydrophilic polymer and enteric polymer such as acrylate copolymer.Said preparation can be from the Eli Lilly ﹠amp of the U.S.; Co., Ltd. is with trade name Ceclor (CD) Obtain, its in by the harmonization of the stomach small intestinal by the time discharge cefaclor with constant speed.
Though above-mentioned preparation can the slow release cefaclor, but still needs take at least twice every day.In addition, they discharge most active component in the bottom of intestinal usually, but cefaclor is not absorbed in this partial enteral.
Moreover, because conventional sustained-release only is to be used for discharging cefaclor with constant rate of speed, taking once every day, but must use a large amount of cefaclors, and therefore because excessive initial drug serum-concentration causes unwished-for side effect.
Therefore, still need to develop more effective cefaclor drug-supplying system.
The invention summary
Therefore, main purpose of the present invention provides a kind of new sustained release compositions that comprises cefaclor.
According to the present invention, the slow releasing composition that is provided comprises the cefaclor of 30-90 weight %, water-soluble rising property (hydroswelling) polymer of 5-60 weight % and the salt of 1-10 weight % in the weight of said composition, described salt can be in the gastric juice environment carbon dioxide gas.Slow releasing preparation provided by the invention can be administered once and administration every day secondary every day.
The accompanying drawing summary
Above-mentioned and other purposes of the present invention and feature will become more obvious by the description below in conjunction with accompanying drawing, in the accompanying drawings:
Fig. 1 be presented at cefaclor in the Canis familiaris L. of respectively administration preparation of the present invention (◆) and commercially available cefaclor capsule () concentration over time.
The detailed description of invention
Composition of the present invention can be in gastric juice continuous release Cefaclor within about 24 hours time in a controlled manner. This performance produces owing to being used in combination water-soluble rising property polymer substrate and foaming agent, and described foaming agent produces carbon dioxide when contacting with acidic gastric juice. That is to say that when composition of the present invention entered in the stomach, its swelling also became floatability owing to foam. Then the composition of this swelling and foaming swims in the upper strata of gastric juice, and keeps the floating long time at this, and water-soluble the rising property polymer substrate by swelling stably discharges Cefaclor simultaneously.
The amount of the Cefaclor in the present invention's slow releasing composition with the weighing scale of said composition, is the 30-90 % by weight, preferred 60-90 % by weight.
Water-soluble the rising property polymer that compositions of the present invention comprised can be in gastric environment swelling.Representative water-soluble the rising property polymer that can be used among the present invention comprises hydroxypropyl cellulose (HPC), hydroxypropyl emthylcellulose (HPMC), sodium carboxymethyl cellulose, polyvinylpyrrolidone, sodium alginate and their mixture, wherein preferred hydroxypropyl emthylcellulose (HPMC) and sodium carboxymethyl cellulose.In the weight of the present invention's slow releasing composition, the amount of described water-soluble rising property polymer in compositions is 5-60 weight %.By regulating the amount of this water-soluble rising property polymer, the rate of release of the cefaclor in the present composition in gastric juice also can be adjusted.Along with the increase of water-soluble rising property polymer content, the rate of release of cefaclor descends.
Compositions of the present invention also comprises carbonate or bicarbonate, as the foaming agent that can produce carbon dioxide when contacting with gastric juice.The example of these salt is sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium sesquicarbonate and their mixture, wherein is preferably sodium bicarbonate.In the weight of compositions, the use amount of foaming agent is 1-10 weight %, is preferably 1-5 weight %.Use excessive sodium bicarbonate will produce excessive carbon dioxide gas, can stimulate stomach thus, make the preparation disintegrate, and lose sustained release property.
Compositions of the present invention also can comprise organic acid such as citric acid, tartaric acid, maleic acid and their mixture, and in the gross weight of compositions, this organic acid amount is 1-10 weight %.Organic acid can play the effect of pH buffer agent.That is to say that organic acid can prevent because the temporary rising of pH that the absorption of food causes.
Compositions of the present invention also can comprise foamed damping agent such as calcium carbonate, magnesium carbonate and their mixture, and in the gross weight of compositions, the amount of this buffer agent is 1-10 weight %.The foamed damping agent can prevent the excessive generation of carbon dioxide.
The present invention's the compositions that comprises cefaclor can be mixed with tablet or granule with usual manner, if desired, can add other drug excipient and/or carrier.Acceptable excipient can comprise microcrystalline Cellulose, pectin, sodium alginate, chitosan, Hydroxypropyl Methylcellulose Phathalate, Cellacefate, HPMC-AS, Cellulose acetotrimellitate, gelatin, sucrose, lactose, mannitol, ethyl cellulose, Magnesiumaluminumsilicate and natural or part or complete synthesis hydrophilic gel etc. on the materia medica.
The present invention's the preparation that comprises cefaclor can prepare according to the method for the following stated.
At first, cefaclor and water-soluble rising property polymer and foaming agent mix, and use conventional wet method with the gained granulating mixture then.With gained granule and mix lubricant, then the gained mixture is made tablet with conventional method.The lubricant that can be used among the present invention comprises stearic acid, magnesium stearate, silica sol etc.
Preferably, minimize for making the initial flotation time, and thus in the slow release mode by discharging cefaclor in the buoyant preparation, cefaclor and excipient and water-soluble rising property polymer of a part and foaming agent mixture use conventional wet method with this granulating mixture then.Granule is mixed with water-soluble the rising property polymer and the foaming agent of remainder, and add lubricant.At last the gained mixture is made tablet.
In the method, can in the first step, add organic acid, and the foamed damping agent can be added in two steps.In addition, in the gross weight of used foaming agent, the amount of the foaming agent that comprises in the granule is 10-90 weight %, preferred 50-90 weight %.
The preparation of the present invention that makes thus can discharge cefaclor with controlled stationary mode in the long time, the described time for example is 20 hours, but and be administered once every day, and according to rate of release administration every day secondary.
Following examples and experiment are to be used to be described more specifically the present invention, rather than to the restriction of its scope.
Embodiment 1
The 400g cefaclor is mixed with 20g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate, 10g citric acid, 10g Hydroxypropyl Methylcellulose Phathalate and 2g silica sol.Use 70% ethanol of 140ml to make the mixture granulating, be lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens.
The gained granule is mixed with 60g hydroxypropyl emthylcellulose, 20g calcium carbonate, 5g sodium bicarbonate and 30g sodium carboxymethyl cellulose.To wherein adding 1g silica sol and 3g magnesium stearate, they are in advance by 40 eye mesh screens.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swims in the upper strata, and keeps floating state 6 hours.
Stripping laboratory method II according to regulation in the Pharmacopoeia Coreana (Korean Pharmacopeia) measures cefaclor by the dissolution rate in the tablet, and its condition is under 37 ℃ tablet to be added in the 0.1N hydrochloric acid of 900ml.The result as shown in Table I
Table I
Time (branch) Cumulative leaching rate (%)
15 18.03
30 25.58
60 37.17
120 59.52
240 91.24
480 100.0
Embodiment 2
The 393g cefaclor is mixed with 20g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate, 10g citric acid and 10g Hydroxypropyl Methylcellulose Phathalate.Use 70% ethanol of 140ml to make the mixture granulating, be lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens.
The gained granule is mixed with 80g hydroxypropyl emthylcellulose, 20g calcium carbonate, 5g sodium bicarbonate and 25g microcrystalline Cellulose.To wherein adding the magnesium stearate that 6g passes through in advance by 40 eye mesh screens.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swims in the upper strata, and keeps floating state 6 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table II.
Table II
Time (branch) Cumulative leaching rate (%)
15 8.61
30 14.30
60 23.95
120 41.93
240 71.29
360 94.96
Embodiment 3
393g cefaclor and 20g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate and 10g citric acid are closed.Use 95% ethanol of 120ml to make the mixture granulating, comprise the Hydroxypropyl Methylcellulose Phathalate of 10g in this ethanol, be lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens.
The gained granule is mixed with 70g hydroxypropyl emthylcellulose, 15g calcium carbonate, 15g sodium bicarbonate and 31g microcrystalline Cellulose.The silica sol 3g and the magnesium stearate 3g that in wherein adding, pass through in advance by 40 eye mesh screens.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 6 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table III.
Table III
Time (branch) Cumulative leaching rate (%)
15 15.44
30 22.37
60 35.13
120 60.35
240 90.40
360 100.0
Embodiment 4
The 400g cefaclor is mixed with 20g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate, 10g citric acid and 1g silica sol.Use 95% ethanol of 120ml to make the mixture granulating, comprise the Hydroxypropyl Methylcellulose Phathalate of 10g in this ethanol, be lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens.
The gained granule is mixed with 70g hydroxypropyl emthylcellulose, 20g calcium carbonate, 5g sodium bicarbonate and 40g microcrystalline Cellulose.The silica sol 2g and the magnesium stearate 3g that in wherein adding, pass through in advance by 40 eye mesh screens.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 5 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table IV.
Table IV
Time (branch) Cumulative leaching rate (%)
15 4.33
30 10.58
60 25.93
120 52.33
240 100.0
Embodiment 5
The 393g cefaclor is mixed with 110g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate and 10g citric acid.Use 70% ethanol of 160ml to make the mixture granulating, comprise the Hydroxypropyl Methylcellulose Phathalate of 10g in this ethanol, be lower than 3% at 35 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens
The gained granule is mixed with 10g hydroxypropyl emthylcellulose, 2g sodium bicarbonate and 43g microcrystalline Cellulose.The silica sol 3g and the magnesium stearate 6g that in wherein adding, pass through in advance by 40 eye mesh screens.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 10 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table V.
Table V
Time (branch) Cumulative leaching rate (%)
15 3.29
30 6.53
60 12.93
120 24.67
240 47.50
360 64.23
480 88.56
600 100.0
Embodiment 6
The 393g cefaclor is mixed with 20g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate and 10g citric acid.Use 95% ethanol of 140ml to make the mixture granulating, comprise the Hydroxypropyl Methylcellulose Phathalate of 10g in this ethanol, be lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens
The gained granule is mixed with 60g hydroxypropyl emthylcellulose, 10g sodium bicarbonate, 20g calcium carbonate and 31g microcrystalline Cellulose.The silica sol 3g and the magnesium stearate 3g that in wherein adding, pass through in advance by 40 eye mesh screens.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 6 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table VI.
Table VI
Time (branch) Cumulative leaching rate (%)
15 6.30
30 13.34
60 26.08
120 49.02
240 80.09
360 100.0
Embodiment 7
The 393g cefaclor is mixed with 200g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate and 10g citric acid.Use 70% ethanol of 160ml to make the mixture granulating, comprise the Hydroxypropyl Methylcellulose Phathalate of 10g in this ethanol, be lower than 3% at 35 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens
The gained granule is mixed with 20g hydroxypropyl emthylcellulose, 2g sodium bicarbonate and 43g microcrystalline Cellulose.The silica sol 3g and the magnesium stearate 6g that in wherein adding, pass through in advance by 40 eye mesh screens.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 10 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table VII.
Table VII
Time (hour) Cumulative leaching rate (%)
0.5 2.2
1 5.3
2 10.5
5 23.7
12 50.3
18 75.1
24 100.0
Embodiment 8
The 393g cefaclor is mixed with 30g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate and 10g citric acid.Use 95% ethanol of 170ml to make the mixture granulating, comprise the ethyl cellulose of 10g in this ethanol, be lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens
The gained granule is mixed with 80g hydroxypropyl emthylcellulose, 10g sodium bicarbonate and 20g calcium carbonate, 20g microcrystalline Cellulose, 3g silica sol and 3g magnesium stearate.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 8 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table VIII.
Table VIII
Time (hour) Cumulative leaching rate (%)
0.5 7.94
1 14.80
2 26.60
4 46.34
6 68.99
8 91.69
10 97.65
12 100.0
Embodiment 9
The 393g cefaclor is mixed with 55g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate and 10g citric acid.Use 95% ethanol of 190ml to make the mixture granulating, comprise the ethyl cellulose of 30g in this ethanol, be lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens
The gained granule is mixed with 35g hydroxypropyl emthylcellulose, 10g sodium bicarbonate, 20g calcium carbonate, 20g microcrystalline Cellulose, 3g silica sol and 3g magnesium stearate.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 12 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table IX.
Table I X
Time (hour) Cumulative leaching rate (%)
0.5 8.17
1 14.20
2 23.43
4 39.27
6 51.14
8 65.43
10 76.37
12 86.54
14 94.65
16 100.0
Embodiment 10
The 393g cefaclor is mixed with 40g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate and 10g citric acid.Use 95% ethanol of 170ml to make the mixture granulating, comprise the ethyl cellulose of 30g in this ethanol, be lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens
The gained granule is mixed with 50g hydroxypropyl emthylcellulose, 10g sodium bicarbonate, 20g calcium carbonate, 20g microcrystalline Cellulose, 3g silica sol and 3g magnesium stearate.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 20 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result as shown in Table X.
Table X
Time (hour) Cumulative leaching rate (%)
1 9.27
2 16.37
3 29.10
4 38.87
8 47.22
10 54.17
12 60.47
16 73.62
20 83.30
24 97.10
Embodiment 11
The 393g cefaclor is mixed with 110g hydroxypropyl emthylcellulose, 20g calcium carbonate, 10g sodium bicarbonate and 10g citric acid.Use 95% ethanol of 210ml to make the mixture granulating, the hydroxypropyl methyl dimension that comprises 20g in this ethanol is plain, is lower than 3% at 40 ℃ of down dry this granule to water contents, then by passing through in 20 eye mesh screens
The gained granule is mixed with 30g hydroxypropyl emthylcellulose, 10g sodium bicarbonate, 20g calcium carbonate, 20g microcrystalline Cellulose, 3g silica sol and 3g magnesium stearate.The gained mixture uses conventional tablet machine to be pressed into tablet.
When being added to the gained tablet in the simulated gastric fluid, it swam in the upper strata 30 seconds, and still kept floating state 20 hours.
As the dissolution rate of measurement cefaclor as described in the embodiment 1, the result is shown in Table X I.
Table X I
Time (hour) Cumulative leaching rate (%)
1 5.79
2 10.10
4 17.41
6 30.18
8 42.43
10 55.63
12 67.54
16 76.43
20 86.27
24 100.0
Stripping experiment in the body
The tablet that contrast prepares according to embodiment 4 in the experiment in the body that uses the Beagle Canis familiaris L. (cefaclor content: 375mg) with commercially available cefaclor capsule (Lilly Co., cefaclor content: 375mg).Before 200ml water administration testing drug, made the Canis familiaris L. fasting 12 hours.Blood sample 1.5ml is taked from every Canis familiaris L. respectively in 0.5,1,2,3,4,6,8,10 and 12 hour interval after administration, and is centrifugal under 3000rpm then, and uses methanol extraction.With the cefaclor concentration in the high-efficient liquid phase color spectrometry blood sample, the result as shown in Figure 1.
As shown in Figure 1, the compositions (◆) that makes according to the present invention is discharging cefaclor in better mode than commercially available cefaclor capsule () in the longer time, this show compositions of the present invention than conventional composition more excellent aspect the sustained release property.
Though described the present invention according to specific embodiment, it should be understood that those skilled in the art also can carry out various changes and improvements to the present invention, and they dropped on also in the appended claim book institute restricted portion.

Claims (7)

1, a kind of slow releasing composition is characterized in that, in the gross weight of said composition, it comprises the cefaclor of 30-90 weight %, water-soluble the rising property polymer of 5-60 weight % and carbonate or the bicarbonate of 1-10 weight %.
2, compositions as claimed in claim 1, wherein, described carbonate or bicarbonate are selected from following group: sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium sesquicarbonate and their mixture.
3, compositions as claimed in claim 1, wherein, described bicarbonate is a sodium bicarbonate.
4, compositions as claimed in claim 1, wherein, described water-soluble rising property polymer is selected from following group: hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, sodium alginate and their mixture.
5, compositions as claimed in claim 1, it also comprises the organic acid that is selected from following group: citric acid, tartaric acid, maleic acid and their mixture.
6, as claim 1 or 5 described compositionss, it also comprises the foamed damping agent that is selected from following group: calcium carbonate, magnesium carbonate and their mixture.
7, a kind of pharmaceutical preparation, it comprises acceptable excipient and/or carrier on compositions as claimed in claim 1 and the materia medica.
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CN1303291A (en) 2001-07-11
EP1067937A1 (en) 2001-01-17
KR19990079034A (en) 1999-11-05
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WO1999049868A1 (en) 1999-10-07
JP2002509887A (en) 2002-04-02
AU3057299A (en) 1999-10-18

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