CN101516348B - Solid preparation comprising ibuprofen and tranexamic acid - Google Patents
Solid preparation comprising ibuprofen and tranexamic acid Download PDFInfo
- Publication number
- CN101516348B CN101516348B CN2007800315584A CN200780031558A CN101516348B CN 101516348 B CN101516348 B CN 101516348B CN 2007800315584 A CN2007800315584 A CN 2007800315584A CN 200780031558 A CN200780031558 A CN 200780031558A CN 101516348 B CN101516348 B CN 101516348B
- Authority
- CN
- China
- Prior art keywords
- tablet
- ibuprofen
- solid preparation
- acid
- tranexamic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 title claims abstract description 67
- 229960001680 ibuprofen Drugs 0.000 title claims abstract description 67
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 title claims abstract description 58
- 229960000401 tranexamic acid Drugs 0.000 title claims abstract description 58
- 238000002360 preparation method Methods 0.000 title abstract description 95
- 239000007787 solid Substances 0.000 title abstract description 76
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims abstract description 62
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims abstract description 20
- 235000021355 Stearic acid Nutrition 0.000 claims abstract description 17
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000008117 stearic acid Substances 0.000 claims abstract description 17
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- 239000004200 microcrystalline wax Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 1
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- DLRJIFUOBPOJNS-UHFFFAOYSA-N phenetole Chemical compound CCOC1=CC=CC=C1 DLRJIFUOBPOJNS-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- QFRKWSPTCBGLSU-UHFFFAOYSA-M potassium 4-hydroxy-3-methoxybenzene-1-sulfonate Chemical compound [K+].COC1=CC(S([O-])(=O)=O)=CC=C1O QFRKWSPTCBGLSU-UHFFFAOYSA-M 0.000 description 1
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960003910 promethazine Drugs 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229960000953 salsalate Drugs 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 229950000112 serrapeptase Drugs 0.000 description 1
- 108010038132 serratiopeptidase Proteins 0.000 description 1
- 239000010243 sho-seiryu-to Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- JWBPVFVNISJVEM-UHFFFAOYSA-M sodium caffeine benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1.CN1C(=O)N(C)C(=O)C2=C1N=CN2C JWBPVFVNISJVEM-UHFFFAOYSA-M 0.000 description 1
- XYEXKDCAGSHWSD-UHFFFAOYSA-M sodium dibunate Chemical compound [Na+].[O-]S(=O)(=O)C1=C(C(C)(C)C)C=CC2=CC(C(C)(C)C)=CC=C21 XYEXKDCAGSHWSD-UHFFFAOYSA-M 0.000 description 1
- 229960002325 sodium dibunate Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229950006382 sulfogaiacol Drugs 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 229960004636 thonzylamine hydrochloride Drugs 0.000 description 1
- 229960000732 tripelennamine hydrochloride Drugs 0.000 description 1
- 229960001593 triprolidine hydrochloride Drugs 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention discloses a solid preparation comprising ibuprofen and tranexamic acid and showing reduced swelling under high temperature storage conditions. Specifically disclosed is a solid preparation which comprises ibuprofen and tranexamic acid and does not contains any stearic acid metal salt, preferably magnesium stearate, calcium stearate or aluminum stearate.
Description
Technical field
The present invention relates to a kind of solid preparation that be inhibited, that contain ibuprofen and tranexamic acid that under the high temperature preservation condition, expands.
Background technology
Ibuprofen is the medicine that is widely used as non-steroid anti-inflammatory agent (NSAID); To the antiinflammatory of diseases such as beaevais' disease, arthralgia and arthritis, neuralgia and neuritis, pain along the spinal column, symptom and analgesia effectively, in addition to the antiinflammatory of acute worsening period of cold syndrome, acute bronchitis, chronic bronchitis and analgesic etc. also effective.But because ibuprofen has side effect such as gastrointestinal disorders, and analgesic effect is less, so studied the preparation that cooperates with various medicines.
For example reported the antipyretic-antalgic agent (with reference to patent documentation 1) that ibuprofen cooperates with anil class antipyretic-antalgic agent such as bucetins; The preparation that ibuprofen cooperates with caffeine (with reference to patent documentation 2); The analgesic composition that ibuprofen cooperates with codeine (with reference to patent documentation 3 and 4); The antipyretic-antalgic agent that ibuprofen cooperates with acetaminophen (with reference to patent documentation 5 and 6); The antipyretic-antalgic agent (with reference to patent documentation 7) that ibuprofen and acetaminophen and allyl isopropylacetyl urea or bromo valeryl urea cooperate; The coldrex that ibuprofen cooperates with lysozyme chloride (with reference to patent documentation 8); Comprise the antipyretic-antalgic agent (with reference to patent documentation 9) of ibuprofen and tranexamic acid etc.Particularly tranexamic acid is used widely as the medicine with antiplasmine effect, anti-allergic effects, anti-inflammatory effect etc., has developed many with the cooperate preparation of ibuprofen with the tranexamic acid combination.For example reported the antipyretic-antalgic agent (with reference to patent documentation 10) that in ibuprofen and tranexamic acid, further cooperates caffeine; The antipyretic-antalgic compositions (with reference to patent documentation 11) that cooperates ascorbic acid; The pharmaceutical preparation (with reference to patent documentation 12) of non-pyrazoline ketone antipyretic analgesic such as combination acetaminophen; The rhinitis that cooperates isoephedrine and/or phenylephrine is with medical composition (with reference to patent documentation 13); Further cooperate flu that alpha-receptor stimulant such as cathine or isoephedrine and flavonoid constitute with medical composition (with reference to patent documentation 14); Cooperate the medical composition (with reference to patent documentation 15) of clemastine and/or bromine hexylamine etc.
On the other hand; Proposed non-steroid antiinflammatory property carboxylic acids such as opioid analgesicses such as morphine or codeine and diclofenac, naproxen, ketoprofen, ibuprofen are prepared into the method (with reference to patent documentation 16) of the preparation of the multilayer tablet that does not contain stearic acid and stearate.This is because the non-constant of intermiscibility of these compositions, compressibility is low, disintegration time is long, and has coloring, so can not these compositions be prepared into the tablet of monolayer.Therefore also proposed to use the method (with reference to patent documentation 17) of hydrogenated vegetable oil place of magnesium stearate as lubricant.
But; In combination beyond the opioid analgesics such as codeine; Do not report this example, and for example put down in writing the composition that will contain ibuprofen and tranexamic acid etc. in the patent documentation 9 and used magnesium stearate to be prepared into the tablet (patent documentation 9, paragraph numbering [0032]) of every 370mg; Put down in writing the known method according to the record of official preparation general provisions in the patent documentation 11, the composition that will contain ibuprofen and tranexamic acid etc. is prepared into capsule (patent documentation 11, paragraph numbering [0047] and [0048]) with magnesium stearate; In addition, also put down in writing in the patent documentation 15 according to usual way, the composition that will contain tranexamic acid and ibuprofen etc. uses magnesium stearate to be prepared into tablet (patent documentation 15, paragraph numbering [0039]); And the spy opens in the 2006-104186 communique (patent documentation 18), has equally also put down in writing the method for putting down in writing in the tablet item according to Japanese Pharmacopoeia preparation general provisions and has been prepared into tablet (patent documentation 18, paragraph numbering [0012]).Therefore think and contain in the preparation of ibuprofen that the undesirable effect of stearic acid or stearate is only limited to the combination with opioid analgesics such as codeine.
Patent documentation 1: special public clear 64-8602 communique
Patent documentation 2: special fair 1-24131 communique
Patent documentation 3: the spy opens flat 3-7218 communique
Patent documentation 4: the spy opens flat 5-194227 communique
Patent documentation 5: the spy opens flat 5-148139 communique
Patent documentation 6: the spy opens flat 11-158066 communique
Patent documentation 7: the spy opens flat 5-246845 communique
Patent documentation 8: the spy opens flat 7-188004 communique
Patent documentation 9: the spy opens flat 9-48728 communique
Patent documentation 10: specially permit communique No. 3667381
Patent documentation 11: the spy opens the 2006-1920 communique
Patent documentation 12: the spy opens the 2005-187328 communique
Patent documentation 13: the spy opens the 2005-232128 communique
Patent documentation 14: the spy opens the 2005-194269 communique
Patent documentation 15: the spy opens the 2006-124380 communique
Patent documentation 16: the spy opens clear 62-51625 communique
Patent documentation 17: the flat 10-504557 communique of special table
Patent documentation 18: the spy opens the 2006-104186 communique
Summary of the invention
The inventor etc. study the solid preparation that contains ibuprofen and tranexamic acid; Preserve down at 1～25 ℃ if find; These solid preparations can continue stable chronically the preservation, but under the high temperature preservation condition, can expand, and crackle etc. takes place on preparation.
Therefore, even problem of the present invention provides the solid preparation that also be inhibited, that contain ibuprofen and tranexamic acid that expands when under the high temperature preservation condition, preserving.
In order to solve the solid preparation expansible problem under the high temperature preservation condition that contains ibuprofen and tranexamic acid, the inventor etc. have inquired into this reason.The solid preparation that contains ibuprofen and tranexamic acid expands under the high temperature preservation condition, but can tableted, nor take place painted, different fully with the described tableted problem through cooperating codeine etc. to cause of patent documentation 16 and patent documentation 17.And this expansion is not because the gas generation that composition decomposition etc. are followed causes, and neither cause owing to moisture absorption, throws a flood of light on very difficulty of this reason.
Because the expansion under the high temperature preservation condition takes place when only cooperating ibuprofen and tranexamic acid at the same time, do not expand ibuprofen and tranexamic acid during respectively as single component.Therefore, for example also consider to make separately multilayer tablet or clad sheet to two kinds of compositions to reduce the solution that ibuprofen contacts with tranexamic acid.But the manufacturing of multilayer tablet or clad sheet is numerous and diverse, through this manufacturing cost increase, production efficiency is reduced, and also leaves over the problem at the interfacial dilation of each layer, so the solution that can not say so.Further also consider to carry out the expansion of coating with inhibitory preparation with sugar-coat or film coating etc.But the expansible degree of solid preparation is big, only prevents it is difficult with sugar-coat or film coating.In addition, as carrying out in the past, can be through remaining on 1～25 ℃ to the solid preparation that comprises ibuprofen and tranexamic acid with repression of swelling, but making troubles in the circulation, in the keeping and in the further use.
The inventor etc. are in order to address these problems; Whole compositions to cooperating in the solid preparation study in great detail; Find this problem not only these two kinds of compositions of ibuprofen and tranexamic acid cause, but since the combination of ibuprofen, tranexamic acid and these three kinds of compositions of magnesium stearate cause.And through further discovering, same expansion issues also takes place when calcium stearate and aluminium stearate are used as lubricant, find that this problem does not take place for stearic acid and magnesium silicate also unexpectedly.This shows that stearic acid itself is no problem, nor be the problem of magnesium and these metal ions of calcium itself, but this chemical compound of magnesium stearate, calcium stearate and aluminium stearate causes.
Find thus, when preparation contains the solid preparation of ibuprofen and tranexamic acid,, then can obtain under the high temperature preservation condition, not expanding solid preparation problem, stable if do not use magnesium stearate, calcium stearate or aluminium stearate.In addition, when also finding to make with lubricator,,, can obtain under the high temperature preservation condition, not expanding solid preparation problem, stable, thereby accomplish the present invention through using the lubricant beyond magnesium stearate, calcium stearate or the aluminium stearate as lubricant.
That is, the present invention relates to a kind of solid preparation that contains ibuprofen and tranexamic acid, it is characterized in that: this solid preparation does not contain Metallic stearates, does not preferably contain magnesium stearate, calcium stearate and aluminium stearate.
In addition, the present invention relates to a kind of solid preparation that contains ibuprofen and tranexamic acid, it is characterized in that: use the lubricant beyond the Metallic stearates as lubricant, preferably use the lubricant beyond magnesium stearate, calcium stearate or the aluminium stearate.
In more detail, the present invention relates to following content.
(1) a kind of solid preparation that contains ibuprofen and tranexamic acid, it is characterized in that: this solid preparation does not contain Metallic stearates.
(2) like above-mentioned (1) described solid preparation, wherein, Metallic stearates is magnesium stearate, calcium stearate or aluminium stearate.
(3) a kind of solid preparation that contains ibuprofen and tranexamic acid, it is characterized in that: this solid preparation does not contain magnesium stearate, calcium stearate and aluminium stearate.
(4) like above-mentioned (1) or (2) described solid preparation, it is the solid preparation that contains ibuprofen and tranexamic acid, it is characterized in that: this solid preparation does not contain Metallic stearates, and contains the lubricant beyond the Metallic stearates.
(5) like above-mentioned (3) or (4) described solid preparation; It is the solid preparation that contains ibuprofen and tranexamic acid; It is characterized in that: this solid preparation does not contain magnesium stearate, calcium stearate and aluminium stearate, and contains the lubricant beyond magnesium stearate, calcium stearate or the aluminium stearate.
(6) like each described solid preparation of above-mentioned (1)～(5), wherein, this solid preparation is a tablet.
(7) a kind of solid preparation that contains ibuprofen and tranexamic acid is characterized in that: this solid preparation uses Metallic stearates lubricant in addition as lubricant.
(8) like above-mentioned (7) described solid preparation, wherein, Metallic stearates is magnesium stearate, calcium stearate or aluminium stearate.
(9) a kind of solid preparation that contains ibuprofen and tranexamic acid is characterized in that: this solid preparation uses magnesium stearate, calcium stearate or aluminium stearate lubricant in addition as lubricant.
(10) like each described solid preparation of above-mentioned (7)～(9); Wherein, select the group that lubricant beyond the Metallic stearates or the lubricant beyond magnesium stearate, calcium stearate or the aluminium stearate constitute for single higher alkyl esters monometallic salt, sucrose fatty acid ester, light silicon dioxide, wax, hydrogenated vegetable oils, polyethylene glycols, sodium lauryl sulfate, fatty acid glyceride and castor oil hydrogenated from Talcum, stearic acid, silicon dioxide, binary acid more than a kind or 2 kinds.
(11) like each described solid preparation of above-mentioned (7)～(10); Wherein, lubricant beyond the Metallic stearates or the lubricant beyond magnesium stearate, calcium stearate or the aluminium stearate for select the group that constitutes from Talcum, stearic acid, sodium stearyl fumarate, sucrose fatty acid ester, Brazil wax and fatty acid glyceride more than a kind or 2 kinds.
(12) like each described solid preparation of above-mentioned (7)～(11), wherein, this solid preparation is a tablet.
(13) the expansible method of a kind of inhibition solid preparation, it is characterized in that: this solid preparation is the solid preparation that contains ibuprofen and tranexamic acid, does not contain Metallic stearates in this solid preparation.
According to the present invention, even can obtain under the high temperature preservation condition, containing the expansion solid preparation that also be inhibited, stable of the solid preparation of ibuprofen and tranexamic acid.
The specific embodiment
Be included in the ibuprofen in the solid preparation of the present invention, not only can use ibuprofen, also can use its pharmaceutically acceptable salt (alkali metal salt or alkali earth metal salts such as sodium salt, calcium salt; Acylates such as arginine salt, lysinate etc.), it can use commercially available product.Ratio to being included in the ibuprofen in the solid preparation of the present invention has no particular limits; See from the viewpoint of pharmacological effect, with respect to solid preparation generally speaking, be preferably 1～70 quality % in the ibuprofen monomer; More preferably 5～60 quality % are preferably 7～50 quality % especially.
Be included in the tranexamic acid in the solid preparation of the present invention, not only can use tranexamic acid, also can use its pharmaceutically acceptable salt (alkali metal salt or alkali earth metal salts such as potassium salt, magnesium salt; Inorganic acid salts such as sulfate etc.), it can use commercially available product.Ratio to being included in the tranexamic acid in the solid preparation of the present invention has no particular limits; See from the viewpoint of pharmacological effect, with respect to solid preparation generally speaking, be preferably 1～70 quality % in the tranexamic acid monomer; More preferably 5～60 quality % are preferably 7～50 quality % especially.
Solid preparation of the present invention causes solid preparation expansible Metallic stearates, particularly magnesium stearate, calcium stearate and aluminium stearate when it is characterized in that not containing the high temperature preservation.As required, solid preparation of the present invention can cooperate the alternative composition of this Metallic stearates.As this composition; For example have as the composition beyond the Metallic stearates such as the known magnesium stearate of lubricant, calcium stearate, aluminium stearate, these compositions are called " lubricant beyond the Metallic stearates " or " lubricant beyond magnesium stearate, calcium stearate or the aluminium stearate (following also slightly be called sometimes " lubricant beyond the StMg ") " in the present invention.Promptly; Solid preparation of the present invention is the solid preparation that contains ibuprofen and tranexamic acid; It is characterized in that this solid preparation does not contain Metallic stearates, preferably do not contain magnesium stearate, calcium stearate and aluminium stearate, as required; Contain the lubricant beyond the Metallic stearates, preferably contain the composition that constitutes by the lubricant beyond magnesium stearate, calcium stearate or the aluminium stearate.
" Metallic stearates beyond lubricant " among the present invention or " lubricant beyond the StMg " be as the operable material of lubricant, so long as beyond the stearate, beyond the preferred Metallic stearates, to be more preferably magnesium stearate, calcium stearate or aluminium stearate lubricant in addition just passable.As the Metallic stearates class, calcium stearate, magnesium stearate, aluminium stearate etc. are for example arranged.Solid preparation of the present invention is characterized in that not containing these Metallic stearates, does not preferably contain magnesium stearate, calcium stearate and aluminium stearate.This " lubricant beyond the Metallic stearates " or " lubricant beyond the StMg " for example have from Talcum; Stearic acid; Silicon dioxide; Single higher alkyl esters monometallic salt of binary acid (for example fumaric acid list higher alkyl esters slaine such as sodium stearyl fumarate); Sucrose fatty acid ester (for example sucrose high-grade aliphatic ester such as sucrose palmitate); Light silicon dioxide; (Brazil wax, haze tallow (Japan wax (haze wax), lacquer tree fat (urushiwax)), castor etc. are from the wax of plant for wax; Cera Flava, white beeswax, spermaceti, refined wool fat etc. are from the wax of animal; Paraffin, microwax etc. are from the wax of oil; Montan wax, refining montan wax etc. are from native paraffin such as the wax of mineral or synthetic wax etc.); Hydrogenated vegetable oils; Polyethylene glycols; Sodium lauryl sulfate; Select in the group that fatty acid glyceride glycerol high-grade aliphatic esters such as (for example) palmitins and castor oil hydrogenated constitute more than a kind or 2 kinds.The preferred lubricant of the present invention; For example have from the group that Talcum, stearic acid, fumaric acid list senior alkyl alkali metal salt, sucrose fatty acid ester, wax and fatty acid glyceride constitute, select more than a kind or 2 kinds, especially preferably from the group that Talcum, stearic acid, sodium stearyl fumarate, sucrose fatty acid ester, Brazil wax and fatty acid glyceride constitute, select more than a kind or 2 kinds.
In addition, as the fatty acid or the higher fatty acids that form ester, carbon numbers such as lauric acid, myristic acid, Palmic acid, stearic acid, oleic acid 、 behenic acid are for example arranged is 10～40, be preferably 10～30 alkanoic acid and alkenoic acid.When these fatty acids and sucrose or glycerol form ester, also can use the identical or different fatty acid of one or more hydroxyls to form ester.As senior alkyl, carbon numbers such as lauryl, myristyl, stearyl are for example arranged is 10～40, be preferably 15～35 senior alkyl.
" lubricant beyond the Metallic stearates " that contains in the solid preparation of the present invention or " lubricant beyond the StMg " all can use commercially available product.For example, as steatitic commercially available prod TALC MS, TALC MICRO ACE (Japanese タ Le Network society make) etc. are arranged." lubricant beyond the Metallic stearates " that contains in the solid preparation of the present invention or the ratio of " lubricant beyond the StMg "; With respect to solid preparation generally speaking; Be preferably 0.1～10 quality %; More preferably 0.2～9 quality % is preferably 0.3～8 quality %, 1～3 quality % especially.When in addition, the use of " lubricant beyond the Metallic stearates " or " lubricant beyond the StMg " is suitable for preparing tablet.
Solid preparation of the present invention also can comprise one or more the medicine beyond ibuprofen and the tranexamic acid, for example optional from analgesic analgesics, hydryllin, anti-tussive agents, narcotine class, bronchodilator, go expectorant agent, hypnosis tranquilizer, vitamins, anti-inflammatory agent, gastric mucosa protectant, crude drug class, tcm prescription, caffeine class etc.
Can enumerate for example aspirin, aluminum acetylsalicylate, acetaminophen, ethenzamide, disalicylic acid, salicylamide, lacto ethyl phenyl ether, sodium salicylate etc. as the antipyretic-antalgic agent.
Can enumerate for example hydrochloric acid nitrogen
Si Ting as hydryllin; Antol (Sumitomo); Clemastine fumarate; Ketotifen fumarate; Diphenylpyraline hydrochloride; Diphhydramine hydrochloride; The hydrochloric acid difeterol; Triprolidine hydrochloride; Tripelennamine hydrochloride; Thonzylamine hydrochloride; The hydrochloric acid fenethazine; Methdilazine hydrochloride; Diphenhydramine salicylate; Diphenyl disulfonic acid carbinoxamine (carbinoxaminediphenyldisulfonic acid); Alimemazine tartrate; The tannic acid diphenhydramine; Tea chloric acid diphenylpyraline; The mebhydrolin napadisilate; Di-2-ethylhexylphosphine oxide salicylic acid promethazine (promethazinemethylenedisalicylate); Carbinoxamine maleate; The dl-chlorphenamine maleate; The d-chlorphenamine maleate; Mequitazine; Phosphoric acid difeterol etc.
Can enumerate for example Hexacol, hydrochloric acid cloperastine, pentoxyverine citrate, citric acid tipepidine, sodium dibunate, dextromethorphan hydrobromide, dextromethorphan phenolphthalin salt (dextromethorphan phenolphthalin salt), extra large benzoic acid tipepidine, fragrant ground toothed oak acid cloperastine, codeine phosphate, dihydrocodeine phosphate etc. as anti-tussive agents.
Can enumerate for example Gnoscopine hydrochloride., narcotine etc. as the narcotine class.
Can enumerate for example dl-mephedrine, dl-methylephedrine saccharin salt (methylephedrine saccharin salt) etc. as bronchodilator.
Can enumerate for example sulfogaiacol, guaifenesin, hydrochloric acid bromine hexylamine, ambroxol hydrochloride, carbocisteine etc. as going the expectorant agent.
Can enumerate bromo valeryl urea, allyl isopropylacetyl urea etc. as the hypnosis tranquilizer.
Can enumerate vitamin B as vitamins
1, vitamin B
2, vitamin C, Hesperidin and its derivant, and their salt etc.
Can enumerate lysozyme chloride, Serrapeptase, glycyrrhizic acid and analog thereof etc. as anti-inflammatory agent.
As gastric mucosa protectant can enumerate glycine, magnesium silicate, synthetic aluminium silicate, synthetic hydrotalcite, magnesium oxide, dihydroxy aluminum glycinate (dihydroxyaluminum aminoacetate), gel aluminum hydroxide, aluminium hydroxide magnesium carbonate combination drying gel, aluminium hydroxide/sodium bicarbonate coprecipitate, aluminium hydroxide/calcium carbonate/magnesium carbonate coprecipitate, magnesium hydroxide/aluminium potassium sulfate coprecipitate, magnesium carbonate, Magnesiumaluminumsilicate etc.
Can enumerate Oxoamidine (Bulbus Allii processed goods), Herba Ephedrae, Fructus Nandinae Domesticae fruit as the crude drug class! Nan real), bark of cherry, Radix Polygalae, Radix Glycyrrhizae, Radix Platycodonis, Semen Plantaginis, Herba Plantaginis, Bulbus Lycoridis Radiatae, Flos Hierochloes adoratae, Bulbus Fritillariae Uninbracteatae, Fructus Foeniculi, Cortex Phellodendri, Rhizoma Coptidis, Rhizoma Curcumae, Flos Matricariae chamomillae, Cortex cinnamomi japonici (Ramulus Cinnamomi), Radix Gentianae, Calculus Bovis, beastly gallbladder (comprising Fel Ursi), Radix Adenophorae (Radix Glehniae), Rhizoma Zingiberis Recens, Rhizoma Atractylodis, Flos Caryophylli, Pericarpium Citri Reticulatae, the Rhizoma Atractylodis Macrocephalae, Pheretima, Rhizoma Panacis Japonici, Radix Ginseng etc.
Can enumerate GEGEN TANG, guizhi decoction, Xiangsu San, CHAIHU GUIZHI TANG, Herba Sidae Rhombifoliae soup, XIAOQINGLONG TANG, Maimendong Tang, BANXIA HOUPU TANG, Ephedrae Decoction etc. as tcm prescription.
Can enumerate as the caffeine class, for example Caffeine Anhydrous, caffeine, caffeine sodium benzoate etc.
Solid preparation of the present invention can also comprise as the excipient beyond the Metallic stearates of additive, binding agent, disintegrating agent etc.
Can enumerate lactose, starch based, crystalline cellulose, sucrose, mannitol etc. as excipient.Can enumerate hydroxypropyl emthylcellulose, hydroxypropyl cellulose, gelatin, alphalysed starch, polyvinylpyrrolidone, polyvinyl alcohol, amylopectin etc. as binding agent.Can enumerate carboxymethyl cellulose, carboxymethylcellulose calcium, low-substituted hydroxypropyl cellulose, crospovidone, cross-linking sodium carboxymethyl cellulose etc. as disintegrating agent.
Can enumerate for example capsule, pill, granule, tablet, powder etc. as the dosage form of solid preparation of the present invention, special preferred tablet.Solid preparation also can carry out coating with sugar-coat or film coating etc.
According to usual way, can make solid preparation of the present invention.For example; When dosage form is tablet; Make it comprise ibuprofen, tranexamic acid, the normally used various additives of preparation tablet and required various medicines, mix or pelletize according to usual way, as required; With carrying out tabletting after mixture that obtains or the mix lubricant beyond pelletize thing and the Metallic stearates, can prepare solid preparation of the present invention.In addition; Use ibuprofen, tranexamic acid, the normally used various additives of preparation tablet and required various medicines; According to usual way ibuprofen and tranexamic acid are separated pelletize; As required, with carrying out tabletting after the mix lubricant beyond these pelletize things and the Metallic stearates, can prepare solid preparation of the present invention.
Use embodiment further to specify the present invention below, but the invention is not restricted to these embodiment.
Embodiment 1
Trade name Japanese Pharmacopoeia ibuprofen), tranexamic acid 840g (make: by the first Off ア Le マ テ Star Network trade name Japanese Pharmacopoeia tranexamic acid), hydroxypropyl cellulose 96g, crystalline cellulose 1104g, cross-linking sodium carboxymethyl cellulose 200g drop into the high-speed stirred comminutor (industry of dark river is made: after the FS-10 type) mixing, add kneading behind the pure water 1000g ibuprofen 900g ianthone Mi swamp creek reason is made:.This granulation thing is dropped into fluid bed dryer, and (Off ロ イ Application ト industry is made: the FLO-5 type) after the drying, (Seiko of field, ridge is made: the ND-10 type) carry out whole grain with pelletizing machine.With this granulate thing 3140g and Talcum (Japanese タ Le Network manufacturing: 40g input mixer (コ ト Block キ manufacturing: the PM50 type) after mixing trade name TALC MS); With the tablet machine ianthone field iron worker manufacturing of diameter 8.5mm drift is installed: the tabletting HT-AP18SS type) obtains sheet and heavily is 12000 in the tablet of 265mg.
Embodiment 2
(Japanese oils and fats manufacturing: trade name Japanese Pharmacopoeia stearic acid) 60g replaces the Talcum of embodiment 1, and crystalline cellulose is 1084g, and other are identical with embodiment 1, obtain tablet to cooperate stearic acid.
Comparative example 1
Cooperate magnesium stearate 40g to replace the Talcum of embodiment 1, other are identical with embodiment 1, obtain tablet.
Comparative example 2
Cooperate calcium stearate 40g to replace the Talcum of embodiment 1, other are identical with embodiment 1, obtain tablet.
Comparative example 3
Cooperate aluminium stearate 40g to replace the Talcum of embodiment 1, other are identical with embodiment 1, obtain tablet.
Comparative example 4
Cooperate Talcum 20g and magnesium stearate 20g to replace the Talcum of embodiment 1, other are identical with embodiment 1, obtain tablet.
Test Example 1
Expansible evaluation
To put into vial (5K specification) with each 6 in the tablet of embodiment 2 and comparative example 1～4 preparation through embodiment 1, cover sealing-plug after, in 60 ℃ of thermostatic containers, preserved 3 days.Measure the tablet thickness of preparation just and the tablet thickness after the preservation according to digimatic micrometer (digital micrometer), calculate expansion rate (%) with following formula (1) definition.
Expansion rate (%)=(D-D
0)/D
0* 100 (1)
In the formula, D is the tablet thickness after preserving, D
0It is the tablet thickness that just prepares.
Per 6 prescription of the tablet that embodiment 1 and embodiment 2 and comparative example 1～4 obtain (unit: the mg/6 sheet) and result of the test be illustrated in the following table 1.
Table 1 (unit: the mg/6 sheet)
| Embodiment 1 | Embodiment 2 | Comparative example 1 | Comparative example 2 | Comparative example 3 | Comparative example 4 | |
| Ibuprofen | 450 | ?450 | ?450 | 450 | 450 | ?450 |
| Tranexamic acid | 420 | ?420 | ?420 | 420 | 420 | ?420 |
| Hydroxypropyl cellulose | 48 | ?48 | ?48 | 48 | 48 | ?48 |
| Crystalline cellulose | 552 | ?542 | ?552 | 552 | 552 | ?552 |
| Cross-linking sodium carboxymethyl cellulose | 100 | ?100 | ?100 | 100 | 100 | ?100 |
| Talcum | 20 | ?--- | ?--- | --- | --- | ?10 |
| Stearic acid | --- | ?30 | ?--- | --- | --- | ?--- |
| Magnesium stearate | --- | ?--- | ?20 | --- | --- | ?10 |
| Calcium stearate | --- | ?--- | ?--- | 20 | --- | ?--- |
| Aluminium stearate | --- | ?--- | ?--- | --- | 20 | ?--- |
| Add up to | 1590 | ?1590 | ?1590 | 1590 | 1590 | ?1590 |
| 60 ℃ of expansion rates (%) of preserving after 3 days | 5 | ?6 | ?32 | 26 | 30 | ?28 |
Containing ibuprofen and tranexamic acid, do not containing in the solid preparation of the present invention (embodiment 1 and embodiment 2) of Metallic stearates, 60 ℃ of expansion rates of preserving after 3 days are very little, are respectively 5% and 6%.On the other hand, having confirmed to cooperate the tablet expansion rate of magnesium stearate (comparative example 1), calcium stearate (comparative example 2), aluminium stearate (comparative example 3) big, is 32%, 26%, 30%.Further observe, tablet (comparative example 4) expansion rate that a steatitic part is changed into magnesium stearate is also big, is 28%, even confirm to contain Talcum, because Metallic stearates such as cooperation magnesium stearate also can not get effect of the present invention.In addition; Because comparative example 1～4 expansion rate is big, so become fragile, breaking with damaged of tablet taken place easily; And solid preparation of the present invention (embodiment 1 with embodiment 2) though after preserving 60 ℃ of such exacting terms under, do not take place yet tablet break and damaged, be indicated as stable tablet.
Reference example 1
Use ibuprofen 420 mass parts, tranexamic acid 450 mass parts, use with embodiment 1 identical method to prepare tablet.
This tablet in 60 ℃ of 1 weeks of preservation, is not observed expansion.Think that this is owing to do not contain the cause of Metallic stearates.
Reference example 2
Use ibuprofen 420 mass parts, magnesium stearate 10 mass parts, use with embodiment 1 identical method to prepare tablet.
This tablet in 60 ℃ of 1 weeks of preservation, is not observed expansion.Think that this is owing to do not cooperate the cause of tranexamic acid.
Reference example 3
Use tranexamic acid 450 mass parts, magnesium stearate 10 mass parts, use with embodiment 1 identical method to prepare tablet.
This tablet in 60 ℃ of 1 weeks of preservation, is not observed expansion.Think that this is owing to do not cooperate the cause of ibuprofen.
Embodiment 3
Ibuprofen 1350g rice swamp creek reason is made: trade name Japanese Pharmacopoeia ibuprofen), tranexamic acid 1260g (the one or three altogether プ ロ Off ア one マ make: trade name Japanese Pharmacopoeia tranexamic acid), hydroxypropyl cellulose 145.8g, cross-linking sodium carboxymethyl cellulose 486g, D-mannitol 1521g drop into the high-speed stirred comminutor (industry of dark river is made: after the FS-10 type) mixing, add kneading behind the pure water 466g.This granulation thing is dropped into fluid bed dryer, and (Off ロ イ Application ト industry is made: the FLO-5 type) after the drying, (Seiko of field, ridge is made: the ND-10 type) carry out whole grain with pelletizing machine.With this granulate thing 4762.8g and sodium stearyl fumarate 97.2g (JRS PHARMA society manufacturing: trade name プ Le one Block) drop into mixer (コ ト Block キ manufacturing: the PM50 type) after the mixing; With the tablet machine ianthone field iron worker manufacturing of diameter 8.5mm drift is installed: the tabletting HT-AP18SS type) obtains sheet and heavily is 18000 in the tablet of 270mg.
Embodiment 4
(reason is ground the manufacturing of PVC タ ミ Application: trade name Port エ system TR-FB) 97.2g replaces the sodium stearyl fumarate of embodiment 3, and other are identical with embodiment 3, obtain tablet to append the cooperation fatty acid glyceride.
Embodiment 5
(Mitsubishi Chemical's Off one ズ makes: trade name Ryoto SugarEster B-370F) 97.2g replaces the sodium stearyl fumarate of embodiment 3, and other are identical with embodiment 3, obtain tablet to append the cooperation sucrose fatty acid ester.
Embodiment 6
(Off ロ イ Application ト industry is made: trade name PolishingWax-103) 97.2g replaces the sodium stearyl fumarate of embodiment 3, and other are identical with embodiment 3, obtain tablet to append the cooperation Brazil wax.
Comparative example 5
(peaceful chemistry is made: trade name vegetalitas magnesium stearate) 97.2g replaces the sodium stearyl fumarate of embodiment 3, and other are identical with embodiment 3, obtain tablet to append the cooperation magnesium stearate.
Comparative example 6
(peaceful chemistry is made: trade name vegetalitas calcium stearate) 97.2g replaces the sodium stearyl fumarate of embodiment 3, and other are identical with embodiment 3, obtain tablet to append the cooperation calcium stearate.
Test Example 2
Expansible evaluation
To put into vial (2K specification) through each 1 in the tablet of embodiment 3～6 and comparative example 5 and comparative example 6 preparations; After covering sealing-plug, in 50 ℃ of thermostatic containers, preserved for 2 weeks, in 60 ℃ of thermostatic containers, preserve 1 day (just the tablet of embodiment 6 preparations was only preserved 1 day in 60 ℃).Go out expansion rate (%) with Test Example 1 identical calculations.
The prescription that the tablet that embodiment 3～6 and comparative example 5 and comparative example 6 obtain is every (unit: the mg/ sheet) and result of the test be illustrated in the following table 2.
Table 2 (unit: the mg/ sheet)
| Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Comparative example 5 | Comparative example 6 | |
| Ibuprofen | 75.0 | 75.0 | 75.0 | 75.0 | 75.0 | 75.0 |
| Tranexamic acid | 70.0 | 70.0 | 70.0 | 70.0 | 70.0 | 70.0 |
| Hydroxypropyl cellulose | 8.1 | 8.1 | 8.1 | 8.1 | 8.1 | 8.1 |
| Cross-linking sodium carboxymethyl cellulose | 27.0 | 27.0 | 27.0 | 27.0 | 27.0 | 27.0 |
| The D-mannitol | 84.5 | 84.5 | 84.5 | 84.5 | 84.5 | 84.5 |
| Sodium stearyl fumarate | 5.4 | - | - | - | - | - |
| Fatty acid glyceride | - | 5.4 | - | - | - | - |
| Sucrose fatty acid ester | - | - | 5.4 | - | - | - |
| Brazil wax | - | - | - | 5.4 | - | - |
| Magnesium stearate | - | - | - | - | 5.4 | - |
| Calcium stearate | - | - | - | - | - | 5.4 |
| Add up to | 270 | 270 | 270 | 270 | 270 | 270 |
| 60 ℃ of expansion rates (%) of preserving after 1 day | 2.6 | 6.1 | 5.1 | 4.4 | 22.8 | 20.9 |
| 50 ℃ of expansion rates (%) of preserving after 2 weeks | 2.1 | 3.8 | 3.1 | - | 29.6 | 19.8 |
Cooperate in the preparation (comparative example 5) of Metallic stearates magnesium stearate, preserve 1 day, the 50 ℃ expansion rates after 2 weeks of preservation for 60 ℃ and be respectively 22.8%, 29.6%, confirmed high expansion rate.In addition, cooperate in the preparation (comparative example 6) of Metallic stearates calcium stearate, preserve 1 day, the 50 ℃ expansion rates after 2 weeks of preservation for 60 ℃ and be respectively 20.9%, 19.8%, confirmed high expansion rate.On the other hand, contain ibuprofen and tranexamic acid, not contain the expansion rates that 60 ℃ of the solid preparations of the present invention (embodiment 3～6) of Metallic stearates preserve after 1 day very little, is respectively 2.6%, 6.1%, 5.1%, 4.4%.In addition, the expansion rate that 50 ℃ of solid preparations of the present invention (embodiment 3～5) were preserved after 2 weeks is very little, is respectively 2.1%, 3.8%, 3.1%, has confirmed that significant expansion suppresses effect.
In addition; Because comparative example 5 is big with comparative example 6 expansion rates, so become fragile, breaking with damaged of tablet taken place easily; And solid preparation of the present invention (embodiment 3～6) is indicated as stable tablet even the breaking with damaged of tablet do not taken place yet after preserving under the hot conditions of above-mentioned harshness.
Industrial applicibility
Even the present invention provides a kind of high temperature to preserve the solid preparation that contains ibuprofen and tranexamic acid that also do not expand, stable.The known preparation that contains ibuprofen and tranexamic acid not only can obtain the drug effect that these compositions have, and also can obtain the additional effect that drug effect strengthens, side effect reduces.Therefore, the present invention can provide the pharmaceutical preparation of usefulness through stable dosage form, and can long preservation and safety circulation under common weather conditions, and is also very useful on the industry.
Claims (3)
1. tablet that contains ibuprofen and tranexamic acid; It is characterized in that: this tablet does not contain Metallic stearates, the lubricant of this tablet for from the group that Talcum, stearic acid, sodium stearyl fumarate, sucrose fatty acid ester, Brazil wax and fatty acid glyceride constitute, select more than a kind or 2 kinds.
2. tablet that contains ibuprofen and tranexamic acid is characterized in that: the lubricant of this tablet for select the group that constitutes from Talcum, stearic acid, sodium stearyl fumarate, Brazil wax and fatty acid glyceride more than a kind or 2 kinds.
3. one kind is suppressed the expansible method of tablet; It is characterized in that: said tablet is the tablet that contains ibuprofen and tranexamic acid; Make and do not contain Metallic stearates in this tablet, the lubricant of this tablet for from the group that Talcum, stearic acid, sodium stearyl fumarate, sucrose fatty acid ester, Brazil wax and fatty acid glyceride constitute, select more than a kind or 2 kinds.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP273656/2006 | 2006-10-05 | ||
| JP2006273656 | 2006-10-05 | ||
| PCT/JP2007/001080 WO2008044331A1 (en) | 2006-10-05 | 2007-10-04 | Solid preparation comprising ibuprofen and tranexamic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101516348A CN101516348A (en) | 2009-08-26 |
| CN101516348B true CN101516348B (en) | 2012-02-08 |
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|---|---|---|---|
| CN2007800315584A Expired - Fee Related CN101516348B (en) | 2006-10-05 | 2007-10-04 | Solid preparation comprising ibuprofen and tranexamic acid |
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| Country | Link |
|---|---|
| JP (1) | JPWO2008044331A1 (en) |
| KR (1) | KR20090065513A (en) |
| CN (1) | CN101516348B (en) |
| TW (1) | TW200820994A (en) |
| WO (1) | WO2008044331A1 (en) |
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| JP2008266270A (en) * | 2007-04-25 | 2008-11-06 | Kowa Co | Solid preparation containing ibuprofen, tranexamic acid and sugar alcohol |
| WO2016121925A1 (en) * | 2015-01-30 | 2016-08-04 | 協和発酵バイオ株式会社 | Tablet containing high proportion of functional substance, and manufacturing method for said tablet |
| JP6907470B2 (en) * | 2015-06-12 | 2021-07-21 | 大正製薬株式会社 | Solid formulation |
| JP7111051B2 (en) * | 2019-04-19 | 2022-08-02 | 日油株式会社 | Wax expanding agent and wax composition containing same |
| CN110721169A (en) * | 2019-11-29 | 2020-01-24 | 湖南洞庭药业股份有限公司 | Preparation method of tranexamic acid tablets |
| CN112972399B (en) * | 2021-03-03 | 2022-09-16 | 天津大学 | Ibuprofen-loaded o-vanillin composite particle and preparation method thereof |
| CN115856160B (en) * | 2023-02-28 | 2023-06-06 | 长沙晶易医药科技股份有限公司 | Method for measuring content of related substances in compound tranexamic acid tablet |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006001920A (en) * | 2004-05-18 | 2006-01-05 | Grelan Pharmaceut Co Ltd | Medicinal preparation |
| JP2006124380A (en) * | 2004-09-29 | 2006-05-18 | Dai Ichi Seiyaku Co Ltd | Medicine composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ291223A (en) * | 1994-08-23 | 1998-12-23 | Smithkline Beecham Plc | Medicament containing ibuprofen and codeine, and a carrier containing a hydrogenated vegetable oil as a lubricant |
| JP3667381B2 (en) * | 1995-03-27 | 2005-07-06 | 株式会社資生堂 | Antipyretic analgesic |
| JP5465824B2 (en) * | 2006-03-24 | 2014-04-09 | 第一三共ヘルスケア株式会社 | Pharmaceutical preparation and method for producing the same |
-
2007
- 2007-10-04 CN CN2007800315584A patent/CN101516348B/en not_active Expired - Fee Related
- 2007-10-04 WO PCT/JP2007/001080 patent/WO2008044331A1/en active Application Filing
- 2007-10-04 KR KR1020097005774A patent/KR20090065513A/en not_active Application Discontinuation
- 2007-10-04 JP JP2008538564A patent/JPWO2008044331A1/en active Pending
- 2007-10-04 TW TW096137213A patent/TW200820994A/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006001920A (en) * | 2004-05-18 | 2006-01-05 | Grelan Pharmaceut Co Ltd | Medicinal preparation |
| JP2006124380A (en) * | 2004-09-29 | 2006-05-18 | Dai Ichi Seiyaku Co Ltd | Medicine composition |
Also Published As
| Publication number | Publication date |
|---|---|
| TW200820994A (en) | 2008-05-16 |
| WO2008044331A1 (en) | 2008-04-17 |
| KR20090065513A (en) | 2009-06-22 |
| CN101516348A (en) | 2009-08-26 |
| JPWO2008044331A1 (en) | 2010-02-04 |
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