CN104127392B - A kind of cefalexin capsule agent and preparation technology thereof - Google Patents
A kind of cefalexin capsule agent and preparation technology thereof Download PDFInfo
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- CN104127392B CN104127392B CN201410393597.0A CN201410393597A CN104127392B CN 104127392 B CN104127392 B CN 104127392B CN 201410393597 A CN201410393597 A CN 201410393597A CN 104127392 B CN104127392 B CN 104127392B
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- cefalexin
- capsule
- chitosan
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- polacrilin potassium
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- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 title claims abstract description 92
- 229940106164 cephalexin Drugs 0.000 title claims abstract description 92
- 239000002775 capsule Substances 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 21
- 238000005516 engineering process Methods 0.000 title claims abstract description 17
- 229960000540 polacrilin potassium Drugs 0.000 claims abstract description 25
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 claims abstract description 25
- 229920001661 Chitosan Polymers 0.000 claims abstract description 22
- 239000000314 lubricant Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 6
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound 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 description 3
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 abstract description 26
- 230000000694 effects Effects 0.000 abstract description 10
- 231100000331 toxic Toxicity 0.000 abstract description 4
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- 230000000052 comparative effect Effects 0.000 description 6
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- 238000002474 experimental method Methods 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 235000010603 pastilles Nutrition 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
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- 206010020751 Hypersensitivity Diseases 0.000 description 3
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- 229920002472 Starch Polymers 0.000 description 3
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- 239000002253 acid Substances 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
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- 238000006243 chemical reaction Methods 0.000 description 3
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- 241001478240 Coccus Species 0.000 description 2
- 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 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000004376 Sucralose Substances 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000007667 floating Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
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- 238000011160 research Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 2
- 235000019408 sucralose Nutrition 0.000 description 2
- 239000002132 β-lactam antibiotic Substances 0.000 description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 description 2
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 1
- 241000588624 Acinetobacter calcoaceticus Species 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- 206010061977 Genital infection female Diseases 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 241000588770 Proteus mirabilis Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 241000607764 Shigella dysenteriae Species 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 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 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
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- 150000001875 compounds Chemical class 0.000 description 1
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- 238000001647 drug administration Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000001786 gonorrhea Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
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- 231100000518 lethal Toxicity 0.000 description 1
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- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
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- 229940124588 oral cephalosporin Drugs 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
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- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of cefalexin capsule agent and preparation technology thereof, this capsule is formed in capsule shells by content-filled, containing cefalexin, polacrilin potassium IRP-88 and chitosan in wherein said content。In the cefalexin capsule agent that the present invention relates to, high molecular polymer content is low, better stability of preparation, and preparation technology is simple, and toxic and side effects is little。
Description
Technical field
The invention belongs to technical field of medicine, in particular to the solid orally ingestible of cefalexin, particularly relate to a kind of capsule containing cefalexin。
Background technology
Cefalexin is the semi-synthetic oral cephalosporins of EliLilly company of U.S. listing in 1970, chemistry (6R by name, 7R)-3-methyl-7-[(R)-2-amino-2-phenylacetylamino]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-formic acid, structural formula is as follows:
Cefalexin is that it, by suppressing the synthesis of cell wall, makes cellular content be expanded to dissolving of breaking, thus reaching bactericidal action by the 7 of the 7-ACA derivants synthesized for amino and 3 acetyl-o-methyls carry out chemical improvement, belonging to first generation cephalosporin。
Cefalexin is applicable to streptococcus pneumoniae, Hemolytic streptococcus, product or does not produce penicillinase staphylococcic major part bacterial strain to this product sensitivity。Neisseria is had better antibacterial action by these product, but hemophilus influenza is poor to the sensitivity of these product；Part escherichia coli, proteus mirabilis, salmonella and shigella dysenteriae are had certain antibacterial action by these product。These product are all presented drug resistance by all the other enterobacteriaceae lactobacteriaceaes, acinetobacter calcoaceticus, Pseudomonas aeruginosa, bacteroides fragilis。Fusobacterium and Wei Rong coccus are generally sensitive to these product, and anaerobism gram positive coccus is to this product medium sensitivity。The feature of these product is acidproof, and oral absorption is good。Drug-resistant staphylococcus aureus is had good antibacterial action。It is mainly used in the respiratory tract infection caused by sensitive organism, urinary tract infection, gynecological infections, skin and soft tissue infection, gonorrhea etc.。Cefalexin is very universal in world market, especially applies very extensive in anti-infective therapy, and market share is significantly high, is the little ripe kind of a good effect, side reaction。The cefalexin common formulations of listing has at present: ordinary tablet, dry suspension, dispersible tablet, chewable tablet, granule, capsule, pressing port cavity disintegrating tablet etc.。
Patent CN103462928A discloses a kind of cefalexin capsule agent and preparation method thereof, this capsule is made up of implant and capsule shells, wherein said implant is to be mixed with lubricant by pastille fine powder and obtain, and described pastille fine powder is prepared from by cefalexin, span and neutral inorganic；This preparation method is to join cefalexin in span to stir evenly, and is subsequently adding inorganic salt and adsorbs to obtain pastille fine powder, finally by pastille fine powder and mix lubricant, and capsule charge shell。
Patent CN102648899A discloses a kind of child cefalexin composition, relating to technical field of medicine, the prescription of said composition is made up of cefalexin 25% weight portion, mannitol 25%-75% weight portion, gelatin 2%-4% weight portion, sucralose 0.1%-0.15% weight portion。
The preparation method that patent CN102846568B discloses a kind of cefalexin layering dissolution sheet, taking the gelatinized corn starch that 1.5kg starch preparation quality concentration is 12% in 13kg starch and make binding agent, it be 0.13g, diameter is the substrate of 6.5mm-7mm that the starch of surplus mixes compacting quality with binding agent；Mixed powder is obtained by uniform to crude drug cefalexin powder body and mix lubricant, prepared substrate is put in coating pan, takes 12kg mixed powder and adopt spray gun carboxymethylcellulose sodium solution to make spray successively to be sprayed by mixed powder and wrap on substrate, dry, dry in the air sheet, obtains cefalexin layering dissolution sheet。
Patent CN103432095A discloses cefalexin intragastric floating sustained-release preparation and preparation method thereof, relates to cefalexin intragastric floating sustained-release preparation taking 1 a kind of day and preparation method thereof。With the gross weight gauge of preparation, wherein comprise the active component cefalexin of 65～85 weight %；The water-swellable polymer of 5～15 weight %；4～14 weight % density are less than the hydrophobic material of gastric juice；The foaming agent of 3～7 weight %。Said preparation can within the time of 6～24 hours in the way of stable sustained-release release head cefalexin。
Patent CN103599088A discloses Cephalexin bioadhesive slow-release capsule and preparation method thereof, relate to a kind of day taking the Cephalexin bioadhesive slow-release capsule of 2 times, it is obtained in same hard capsule by cefalexin rapid release small pieces 1 and 5 fills of Cephalexin bioadhesive slow-release small pieces, altogether containing cefalexin active component 250mg。This novelty oral formulations has variable adjustment release characteristics, it may be achieved cefalexin is from rapid release to the characteristic postponing release, it is thus achieved that blood drug level smoothly；Extend the holdup time held on the gastrointestinal tract thus extending soak time to reduce the food impact on fate of drug；Reduce and take number of times, improve patient medication compliance；Reduce gastrointestinal side effect, improve drug safety。
Patent CN103599088A discloses a kind of cefalexin liposome and pharmaceutical composition, and described liposome is made up of the cefalexin of certain part by weight, phospholipid, cholesterol, PLURONICS F87。
Above patent of invention all considers the performance of preparation from cefalexin dissolution aspect, and has not paid close attention to the untoward reaction problem of medicine。Anaphylaxis be cephalosporins medicine the most common be also the most serious untoward reaction, usual cephalosporins medicine drug administration by injection can first carry out skin (or Intradermal) sensitization test, thus getting rid of the probability of allergy to greatest extent, but oral administration does not generally carry out skin test。Cefalexin is oral formulations, and document has many reports causing the even lethal case of severe allergy, anaphylactic shock about cefalexin。
Great many of experiments and research confirm, the type Ⅰ hypersensitivity reaction caused by beta-lactam antibiotic is not caused by antibacterials itself, but relevant with the High-molecular weight polymer impurity existed in medicine。Its incidence rate is relevant with the content of the high molecular polymer existed in medicine。Therefore high molecular polymer is the important indicator of beta-lactam antibiotic quality evaluation, and is the key of Quality control to the analysis of high molecular polymer。The content of the high molecular polymer in control product, to reducing, this type of antibiotic allergy is significant。At present, prior art is not all provided that the cefalexin preparation that a kind of high molecular polymer content is low, good stability, preparation technology are simple, toxic and side effects is little。
Summary of the invention
In view of the deficiencies in the prior art, the purpose of the present inventor is in that to provide cefalexin capsule agent and the preparation technology thereof that a kind of high molecular polymer content is low, good stability, preparation technology are simple, toxic and side effects is little。
First cefalexin polymer Producing reason has been studied by the present inventor。Cefalexin carries out acid, alkali, oxygen failure test and high temperature, high humidity, exposure experiments to light respectively, and result of the test shows that alkali, oxygen destroy all can cause that high molecular polymer content dramatically increases；Acid also has increase, but relatively increases under alkali condition slow；Polymer is also had a significant effect by high temperature, high humidity, and humidity impact is bigger。
The present inventor attempts the moisture in control preparation and adopts damp-prrof packing to improve the stability of preparation, accelerates and long term test shows, the method can not well suppress the increase of high molecular polymer content。The present inventor constantly changes the prescription of preparation, has carried out substantial amounts of test, all fails to obtain satisfied effect。Subsequently, inventor is analyzed the mechanism that cefalexin polymer produces, and the polyreaction of cefalexin also has two ways: a kind of N-type polyreaction being to only occur in parent nucleus, and another kind is the L-type polyreaction that side chain participates in。In acid condition, amino mainly exists cefalexin with the form of quaternary ammonium salt, general only generation N-type polyreaction。In the basic conditions, N-type and L-type polyreaction all can occur。The relative intensity of N-type and L-type polyreaction is by the structures shape of compound。Suppress the generation of polymer, inventors realized that it is not necessary to suppress above two reaction。First, inventor guarantees that cefalexin is in sour environment, under these conditions, only has the N-type polyreaction betiding parent nucleus。Through substantial amounts of experiment, inventor have found that the stability containing polacrilin potassium IRP-88 prescription is substantially better than other adjuvants。But nonetheless, during long-term investigation experiment, polymer still has generation。
Further, inventor's consideration needs to suppress the generation of N-type polyreaction, it is contemplated that add a kind of material with more active amino group, to destroy the intermolecular polymerization of cefalexin。Under the premise of this imagination, inventors performed great many of experiments, it is found surprisingly that, when filler selects chitosan, obtain beyond thought effect, be likely to chitosan macromole in have active hydroxyl and amino, and the amino of relatively cefalexin is active, thus inhibiting the generation of cefalexin polymer。Finally, chitosan is share by inventor with polacrilin potassium IRP-88, constant product quality, accelerates to investigate being basically unchanged of polymer。
Based on above achievement in research, it is an object of the invention to be achieved through the following technical solutions: a kind of cefalexin capsule agent, be content-filled form in capsule shells, containing cefalexin, polacrilin potassium IRP-88 and chitosan in wherein said content。
On the basis of technique scheme, the polacrilin potassium IRP-88 consumption of described cefalexin capsule agent has been carried out following preferred by the present inventor: the weight ratio of cefalexin and polacrilin potassium IRP-88 is 1:0.1-0.5。It is further preferred that the weight ratio of cefalexin and polacrilin potassium IRP-88 is 1:0.3。
On the basis of technique scheme, the chitosan dosage of described cefalexin capsule agent has been carried out following preferred by the present inventor: the weight ratio of cefalexin and chitosan is 1:0.2-0.4。It is further preferred that the weight ratio of cefalexin and chitosan is 1:0.3。
In an embodiment of the present invention, cefalexin capsule agent as above, wherein the weight ratio of cefalexin, polacrilin potassium IRP-88 and chitosan is 1:0.1-0.5:0.2-0.4。
In a most preferred embodiment of the present invention, cefalexin capsule agent as above, wherein the weight ratio of cefalexin, polacrilin potassium IRP-88 and chitosan is 1:0.3:0.3。
Cefalexin capsule agent of the present invention, possibly together with lubricant in wherein said content, described lubricant is one or more in Pulvis Talci, sodium stearyl fumarate and zinc stearate。
It addition, present invention also offers the preparation technology of a kind of above-mentioned cefalexin capsule agent, this technique is direct capsule charge after cefalexin, polacrilin potassium IRP-88, chitosan and lubricant being mixed, and obtains cefalexin capsule agent。
Compared with prior art, in the cefalexin capsule agent that the present invention relates to, high molecular polymer content is low, better stability of preparation, and preparation technology is simple, and toxic and side effects is little。
Detailed description of the invention
Preparation process and the implementation result of the present invention is now further described by following example, embodiment is only for illustration purposes, not limiting the scope of the invention, apparent change and modification that simultaneously those of ordinary skill in the art make according to the present invention are also contained within the scope of the invention。
Embodiment 1
Preparation technology: 80 mesh sieves crossed respectively by cefalexin, polacrilin potassium IRP-88, chitosan, and recipe quantity weighs cefalexin, polacrilin potassium IRP-88, chitosan, add Pulvis Talci mix homogeneously, capsule charge, to obtain final product。
Embodiment 2
Preparation technology: 80 mesh sieves crossed respectively by cefalexin, polacrilin potassium IRP-88, chitosan, and recipe quantity weighs cefalexin, polacrilin potassium IRP-88, chitosan, add zinc stearate mix homogeneously, capsule charge, to obtain final product。
Embodiment 3
Preparation technology: 80 mesh sieves crossed respectively by cefalexin, polacrilin potassium IRP-88, chitosan, and recipe quantity weighs cefalexin, polacrilin potassium IRP-88, chitosan, add zinc stearate mix homogeneously, capsule charge, to obtain final product。
Comparative example 1
Cefalexin 250g
Microcrystalline Cellulose (PH112) 75g
Preparation technology: cefalexin crosses 80 mesh sieves, weighs cefalexin, microcrystalline Cellulose (PH112), mix homogeneously, capsule charge by recipe quantity, to obtain final product。
Comparative example 2
Preparation technology: the cefalexin of recipe quantity is dissolved in the tert-butyl alcohol (solution a) of recipe quantity, stirring and dissolving at normal temperatures, continue stirring, by recipe quantity mannitol, sucralose is dissolved in the purified water (solution b) of prescription purified water total amount 70%-80%；Being dissolved in the purified water (solution c) of prescription water consumption 20%-30% by the gelatin of recipe quantity again, heating is to being completely dissolved；Merging two kinds of solution of above-mentioned b, c and become solution d, and stir, then mixed solution is cooled to less than 5 DEG C。Mixing two kinds of solution of a, d, and stir, with sodium bicarbonate adjustment pH value to 6.0-6.5。According to child cefalexin composition lyophilizing oral cavity disintegration tablet specification, it is determined that after loading amount, being moved in drug-containing dish by loading amount by the medicinal liquid after merging, and put in freeze drying box, medicinal liquid is carried out freezing, evacuation dries, and controls moisture less than 1.0%；Treat that child cefalexin composition lyophilizing oral cavity disintegration tablet is dried, seal in freeze drying box；Cut drug-containing dish after the medicament freezed is taken out freeze drying box, and carry out finished product packing。
Comparative example 3
Cefalexin 250g
Polacrilin potassium IRP-8875g
Zinc stearate 5g
Preparation technology: cefalexin, polacrilin potassium IRP-88 cross 80 mesh sieves respectively, and recipe quantity weighs cefalexin, polacrilin potassium IRP-88, add zinc stearate mix homogeneously, capsule charge, to obtain final product。
High molecular polymer assay in preparation before and after embodiment 4 Acceleration study
High molecular polymer measures。Chromatographic column: TSK-GELG2000SWXL (300mm × 7.8mm, 5 μm)；Mobile phase: 0.005mol/L phosphate buffer [0.005mol/LNaH2PO4Solution-0.005mol/LNa2HPO4(39: 61)]-acetonitrile (95: 5), flow velocity: 0.6ml/min；Detection wavelength: 220nm；Sample size: 20 μ l。Taking sample appropriate, finely ground, accurately weighed, add water the solution made in every 1ml containing cefalexin 2.0mg, as need testing solution (facing by brand-new)；Separately taking cefalexin reference substance appropriate, accurately weighed, add water the solution made in every 1ml containing about 20 μ g, as contrast solution。Respectively sample introduction measures, and by external standard method with the calculated by peak area retention time total impurities less than cefalexin, limit is 1.0%。
Table 1 cefalexin preparation high molecular polymer measurement result (%)
By result in table 1 it can be seen that in the accelerated test process of 6 months, in cefalexin capsule agent prepared by embodiment 1-3, high molecular polymer content substantially increases slowly；And comparative example 1 adopts microcrystalline Cellulose as filler, polymer increases notable；Polymer in comparative example 2 preparation increases rapidly；Comparative example 3 is only with polacrilin potassium IRP-88 as filler, and polymer content is slightly lower。It is notable that above result of the test illustrates that polacrilin potassium IRP-88, chitosan high molecular polymer in inhibitory preparation storage process increases effect。
Claims (4)
1. a cefalexin capsule agent, formed in capsule shells by content-filled, it is characterized in that, described content is directly mixed by cefalexin, polacrilin potassium IRP-88, chitosan and lubricant and is obtained, and wherein the weight ratio of cefalexin, polacrilin potassium IRP-88 and chitosan is 1:0.1-0.5:0.2-0.4。
2. cefalexin capsule agent according to claim 1, it is characterised in that the weight ratio of cefalexin, polacrilin potassium IRP-88 and chitosan is 1:0.3:0.3。
3. cefalexin capsule agent according to claim 1 and 2, it is characterised in that described lubricant is one or more in Pulvis Talci, sodium stearyl fumarate and zinc stearate。
4. the preparation technology of a cefalexin capsule agent according to claim 1, it is characterised in that this technique is direct capsule charge shell after cefalexin, polacrilin potassium IRP-88, chitosan and lubricant being mixed, and obtains cefalexin capsule agent。
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