CN101313898A - Composition for treating gastrointestinal tract diseases - Google Patents
Composition for treating gastrointestinal tract diseases Download PDFInfo
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- CN101313898A CN101313898A CNA2008101162154A CN200810116215A CN101313898A CN 101313898 A CN101313898 A CN 101313898A CN A2008101162154 A CNA2008101162154 A CN A2008101162154A CN 200810116215 A CN200810116215 A CN 200810116215A CN 101313898 A CN101313898 A CN 101313898A
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- China
- Prior art keywords
- pharmaceutical composition
- azulene
- glutaminate
- ulcer
- tablet
- Prior art date
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- 201000010099 disease Diseases 0.000 title claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 9
- 210000001035 gastrointestinal tract Anatomy 0.000 title claims abstract description 6
- 239000000203 mixture Substances 0.000 title claims description 31
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims abstract description 20
- 239000002775 capsule Substances 0.000 claims abstract description 7
- 239000011701 zinc Substances 0.000 claims abstract description 7
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 7
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052797 bismuth Chemical group 0.000 claims abstract description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 4
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical group [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000007910 chewable tablet Substances 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 4
- 239000011777 magnesium Chemical group 0.000 claims abstract description 4
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 4
- 239000006189 buccal tablet Substances 0.000 claims abstract description 3
- 239000006187 pill Substances 0.000 claims abstract description 3
- 239000007901 soft capsule Substances 0.000 claims abstract description 3
- -1 azulene class salt Chemical class 0.000 claims description 11
- 150000001545 azulenes Chemical class 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000003826 tablet Substances 0.000 claims description 8
- 208000007882 Gastritis Diseases 0.000 claims description 6
- 208000010643 digestive system disease Diseases 0.000 claims description 5
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 5
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 3
- 229940068682 chewable tablet Drugs 0.000 claims description 3
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 3
- 229940046011 buccal tablet Drugs 0.000 claims description 2
- 239000006196 drop Substances 0.000 claims description 2
- 210000000214 mouth Anatomy 0.000 claims description 2
- 229940023488 pill Drugs 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 9
- 229930182816 L-glutamine Natural products 0.000 abstract description 7
- HPJYKMSFRBJOSW-JHSUYXJUSA-N Damsin Chemical compound C[C@H]1CC[C@H]2C(=C)C(=O)O[C@H]2[C@]2(C)C(=O)CC[C@@H]12 HPJYKMSFRBJOSW-JHSUYXJUSA-N 0.000 abstract 3
- 239000002131 composite material Substances 0.000 abstract 2
- 239000007935 oral tablet Substances 0.000 abstract 1
- 208000025865 Ulcer Diseases 0.000 description 21
- 231100000397 ulcer Toxicity 0.000 description 21
- 230000000694 effects Effects 0.000 description 9
- 210000002784 stomach Anatomy 0.000 description 8
- 239000008187 granular material Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 230000001476 alcoholic effect Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000007779 soft material Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000001621 bismuth Chemical class 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 3
- 239000011812 mixed powder Substances 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 239000007968 orange flavor Substances 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 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
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000590002 Helicobacter pylori Species 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 210000003489 abdominal muscle Anatomy 0.000 description 2
- 235000010358 acesulfame potassium Nutrition 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- RMCAUKPOUZTMOV-UHFFFAOYSA-N cyclohepta[d][1,3]thiazol-2-one Chemical compound C1=CC=CC=C2SC(=O)N=C21 RMCAUKPOUZTMOV-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 229940037467 helicobacter pylori Drugs 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 150000003751 zinc Chemical class 0.000 description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
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- 108010053835 Catalase Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 235000009161 Espostoa lanata Nutrition 0.000 description 1
- 240000001624 Espostoa lanata Species 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 208000035126 Facies Diseases 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 108010046334 Urease Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910001451 bismuth ion Inorganic materials 0.000 description 1
- 229910000416 bismuth oxide Inorganic materials 0.000 description 1
- 230000035568 catharsis Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- TYIXMATWDRGMPF-UHFFFAOYSA-N dibismuth;oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Bi+3].[Bi+3] TYIXMATWDRGMPF-UHFFFAOYSA-N 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
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- 210000001126 granulation tissue Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
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- 229940111202 pepsin Drugs 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
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- 201000011549 stomach cancer Diseases 0.000 description 1
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- 239000010409 thin film Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 210000002417 xiphoid bone Anatomy 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a composite for treating gastrointestinal tract diseases, comprising L-glutamine and an azulene derivative, wherein, the azulene derivative is a compound shown in formula I, M is zinc, magnesium and bismuth, and n is an integral between 1 and 3.The composite can be made into oral preparation, including troches, capsules, soft capsules, chewable tablets, rapidly disintegrating oral tablets, buccal tablets and dropping pills. The unit preparation content of the L-glutamine is between 0.2 and 3g, and preferable between 0.6 and 2g. The unit preparation content of the azulene derivative is between 0.6 and 10mg, and preferable between 1 and 4.5mg.
Description
Technical field
The present invention relates to a kind of compositions that is used for the treatment of gastroenteropathy, particularly relate to a kind of compositions that includes L-glutaminate and a kind of azulene analog derivative, belong to the pharmaceutical technology field.
Background technology
Azulenoid has following effects: suppress the inflammation that multiple inflammation-causing substance causes, and effect is comparatively lasting; Directly act on the inhibition inflammatory cell by the part and discharge histamine; Increase prostaglandin E in the mucosa
2Synthetic, promote granulation to form and epithelial cell new life; Reduce pepsic activity.Give this product to the ulcer that causes by aspirin, find that aminohexose content increases in the gastric mucosa, and the pepsin amount reduces, and reduces 75% approximately during PH2.0, reduces 78% approximately during PH3.5, has the effect of tangible promotion ulcer healing; NSAID (non-steroidal anti-inflammatory drug) such as aspirin, indomethacin, diclofenac sodium are share separately or with this product give rat, visible combination group medication group aminohexose amount increase separately after 5 or 10 days, ulcer is suppressed, and does not influence the absorption of NSAID (non-steroidal anti-inflammatory drug).Can be used for various idiopathic acute and chronic gastritis clinically, stomach or duodenal ulcer, concurrent Secondary cases gastritis such as gastric cancer or stomach excision, anemia, the concurrent excitability gastritis of disease such as various infectious disease, hepatitis, cholelithiasis.
Some metal ions are to gastroenteropathy, and especially ulcer class disease has special effect.For example, zinc ion can promote mucosa regeneration, quickens ulcer healing, and the cytoprotection of similar prostaglandin is arranged.Zinc is to absorb in duodenum and proximal small bowel, and the main excretion pathway of human body zinc is an intestinal, therefore takes the change that does not cause main organs trace element in the body for a long time, does not also cause accumulating of zinc.Bismuth class medicine neither in and gastric acid; also not gastric acid inhibitory secretion; but under the Gastric pH condition; on the ulcer surface or ulcer substrate granulation tissue form a kind of firm bismuth oxide colloidal precipitation; become the protectiveness thin film; thereby isolated gastric acid; enzyme and food are to the corrosion function of ulcer mucosa; promote the reparation and the healing of chronic ulcer tissue; bismuth ion can promote mucous secretion; can promote ulcer healing to a certain extent; simultaneously because bismuth and bacteria cell wall and wall slurry film formation on every side complex; can suppress the generation of some enzymes of helicobacter pylori; as urease; catalase and lipase etc., these endonuclease capables influence little growing environment of antibacterial, therefore also have the effect of killing helicobacter pylori.Magnesium ion has the catharsis effect, can prevent the constipation symptom that some antiulcerative causes, magnesium also has spasmolytic, abirritative effect simultaneously, can alleviate ulcer patient's pain.
Summary of the invention
The present invention is a kind of compositions that is used for the treatment of gastroenteropathy, includes L-glutaminate and a kind of azulene analog derivative, and wherein said azulene analog derivative is a chemical compound shown in the formula I.
M is zinc, magnesium, bismuth, and n is 1～3 integer.
Said composition can be made into oral formulations, comprises tablet, capsule, soft capsule, chewable tablet, oral cavity disintegration tablet, buccal tablet, drop pill.The unit formulation content of described L-glutaminate is 0.2g～3g, preferred 0.6g-2g.The unit formulation content of described azulene class salt derivative is 0.6mg～10mg, preferred 1mg～4.5mg.This Pharmaceutical composition is used for the treatment of the gastrointestinal tract tract disease, especially is suitable for treating gastritis and peptic ulcer.This compound has been inherited azulenoid and the advantage of L-glutaminate aspect treatment gastrointestinal tract tract disease on the one hand; this prescription was loaded with on the other hand particulate metal ion pair gastrointestinal tract tract disease, especially gastritis and peptic ulcer also have certain protection and therapeutical effect.
By following pharmacological evaluation, further specify the curative effect of azulene class salt derivative of the present invention aspect the treatment digestion disease.
1. experiment modeling:
Fasting feedwater 24h before 135 rat modelings, etherization in the cover+beaker cotton balls nose appends anesthesia, iodine tincture, ethanol routine disinfection, the xiphoid-process lower abdomen hits exactly the 2～2.5cm that hits, and separates abdominal muscle, cuts off peritoneum, gently move to stomach outside the abdomen, at the stomach facies ventralis, body of stomach and pyloric antrum intersection thrust 0.4～0.5mm under the serous coat with microsyringe is flat, inject 10 glacial acetic acid 0.1mL, form pimple, stomach is sent back to, sew up abdominal muscle, skin.
2. experimental technique:
135 rats are divided into 5 groups at random: blank model group, the azulene class bismuth salt+L-glutaminate group (A) of deriving, the azulene class zinc salt+L-glutaminate group (B) of deriving, the azulene class magnesium salt+L-glutaminate group (C) of deriving, Marzulene group.Beginning administration in the 3rd day after the modeling, each group is all irritated stomach by 3mL/ (100g.d), blank model group is given the equal-volume normal saline, each organizes equal every day 1 time, totally 4 weeks. modeling 3d (before the administration), 17d (administration 14d), 31d (administration 28d) divides 3 batches to put to death rat, cut off the abdominal cavity along ventrimeson, take out stomach, cut off along greater gastric curvature, clean with the ice normal saline flushing. gastric mucosa is flattened on flat board, maximum major diameter and the wide footpath of vertical maximum with vernier caliper measurement ulcer. ulcer index (uI) is measured the major diameter and the wideest footpath of ulcer with slide gauge, multiplying each other calculates the ulcer area as ulcer index, ulcer area: S=1/4 * DL * DS * towering, and DL refers to the ulcer major diameter in the formula, DS refers to the ulcer minor axis, the towering 3.14. that gets
3. experimental result:
Table 1 respectively organize rat ulcer index (mm2) and ulcer inhibition rate comparison (mean ± SD, n=15)
The specific embodiment
Can further describe the present invention by the following examples, yet invention of the present invention is not limited to the following examples.
Embodiment 1L-glutamine and the azulene class bismuth salt tablets of deriving
Prescription:
Preparation method:
Derive bismuth salt, microcrystalline Cellulose of azulene class crossed 80 mesh sieves respectively, and mix homogeneously is adopting the equivalent method of progressively increasing to mix with L-glutaminate, and fully stirring makes even, standby; 50% alcoholic solution is joined in the mixed powder, the system soft material, 24 mesh sieves are granulated, drying, 20 mesh sieve granulate add micropowder silica gel, CMS-Na, adopt suitable punch die compressed tablets behind the mix homogeneously, promptly.
If carry out coating for above-mentioned tablet, then obtain coated tablet, can be Film coated tablets, enteric coatel tablets etc.
Embodiment 2:L-glutamine and the azulene class bismuth salt capsule of deriving
Prescription:
Preparation method:
Derive bismuth salt, L-glutaminate of azulene class all crossed 80 mesh sieves, progressively increase behind the method mix homogeneously, add magnesium stearate according to equivalent, mix homogeneously, packing, promptly.
Used capsule shells can be conventional capsule, also can be enteric coated capsule.
Embodiment 3:L-glutamine and the azulene class zinc salt chewable tablet of deriving
Prescription:
Preparation method:
Supplementary materials such as zinc salt, L-glutaminate, xylitol, mannitol that the azulene class is derived are crossed 80 mesh sieves respectively, adopt equivalent incremental method mix homogeneously, add the 2%PVP-k30 alcoholic solution, the system soft material, 16 mesh sieves are granulated, drying, 20 mesh sieve granulate, the correctives, sweeting agent, the fluidizer mix homogeneously that add other, tabletting, promptly.
Embodiment 4:L-glutamine and the azulene class zinc salt dispersible tablet of deriving
Prescription
Preparation method:
Supplementary materials such as zinc salt, L-glutaminate, microcrystalline Cellulose that the azulene class is derived are crossed 80 mesh sieves respectively, adopt equivalent incremental method mix homogeneously, and are standby; Add 75% alcoholic solution, the system soft material, 16 mesh sieves are granulated, drying, 20 mesh sieve granulate add other correctives orange flavor, sweeting agent stevioside, fluidizer micropowder silica gel, mix homogeneously such as disintegrating agent PPVP, L-HPC, tabletting, promptly.
Embodiment 5:L-glutamine and the azulene class magnesium salt effervescent tablet of deriving
Prescription
Preparation method:
L-glutaminate and the azulene class magnesium salt of deriving is crossed 80 mesh sieves, mix homogeneously; Get half mixed powder amount, with the citric acid mix homogeneously, with 50% alcoholic solution system soft material, 18 orders are granulated, drying, 16 order granulate; Get the surplus mixed powder again, mix with sodium carbonate, sodium bicarbonate, the same method is granulated; Two kinds of granules of gained mix, and add other adjuvant, and as mix homogeneously such as PEG6000, orange flavor, acesulfame potassium, sodium chloride, tabletting promptly.
Embodiment 6:L-glutamine and the azulene class bismuth salt particle of deriving
Prescription
Preparation method:
Derive bismuth salt, mannitol, sorbitol of L-glutaminate, azulene class was waited 80 mesh sieves, mix homogeneously; With the 75% alcoholic solution system soft material of 5%PVPk 1,16 orders are granulated, drying, and 12 order granulate add other adjuvant, and as mix homogeneously such as orange flavor, acesulfame potassiums, packing is promptly.
Claims (9)
1. a compositions that is used for the treatment of gastroenteropathy includes L-glutaminate and a kind of azulene analog derivative, and it is characterized in that: described azulene analog derivative is a chemical compound shown in the formula I.
M is zinc, magnesium, bismuth, and n is 1～3 integer.
2. the described Pharmaceutical composition of claim 1 is characterized in that, can be made into oral formulations.
3. the described Pharmaceutical composition of claim 3 is characterized in that, described oral formulations comprises tablet, capsule, soft capsule, chewable tablet, oral cavity disintegration tablet, buccal tablet, drop pill.
4. the described Pharmaceutical composition of claim 1 is characterized in that, the unit formulation content of described L-glutaminate is 0.2g～3g.
5. the described Pharmaceutical composition of claim 4 is characterized in that, the unit formulation content of described L-glutaminate is 0.6g-2g.
6. the described Pharmaceutical composition of claim 1 is characterized in that, the unit formulation content of described azulene class salt derivative is 0.6mg～10mg.
7. the described Pharmaceutical composition of claim 1 is characterized in that, the unit formulation content of described azulene class salt derivative is 1mg～4.5mg.
8. described any one Pharmaceutical composition of claim 1～7 is used for the treatment of the gastrointestinal tract tract disease.
9. described any one Pharmaceutical composition of claim 1～7 is used for the treatment of gastritis and peptic ulcer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101162154A CN101313898A (en) | 2008-07-07 | 2008-07-07 | Composition for treating gastrointestinal tract diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101162154A CN101313898A (en) | 2008-07-07 | 2008-07-07 | Composition for treating gastrointestinal tract diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101313898A true CN101313898A (en) | 2008-12-03 |
Family
ID=40105144
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008101162154A Pending CN101313898A (en) | 2008-07-07 | 2008-07-07 | Composition for treating gastrointestinal tract diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101313898A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120203102A1 (en) * | 2009-09-11 | 2012-08-09 | Mallinckrodt Llc | Azulene and azaazulene systems for imaging, monitoring and therapy |
| CN106692099A (en) * | 2016-12-22 | 2017-05-24 | 南京济群医药科技股份有限公司 | Glutamine acid amide compound film-coated tablets and preparation method thereof |
-
2008
- 2008-07-07 CN CNA2008101162154A patent/CN101313898A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120203102A1 (en) * | 2009-09-11 | 2012-08-09 | Mallinckrodt Llc | Azulene and azaazulene systems for imaging, monitoring and therapy |
| US9226980B2 (en) * | 2009-09-11 | 2016-01-05 | Medibeacon Inc. | Azulene and azaazulene systems for imaging, monitoring and therapy |
| US10059739B2 (en) | 2009-09-11 | 2018-08-28 | Medibeacon Inc. | Non-benzenoid aromatic systems for imaging, monitoring and therapy |
| CN106692099A (en) * | 2016-12-22 | 2017-05-24 | 南京济群医药科技股份有限公司 | Glutamine acid amide compound film-coated tablets and preparation method thereof |
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Open date: 20081203 |