CN107802625A - A kind of pharmaceutical composition and its application - Google Patents
A kind of pharmaceutical composition and its application Download PDFInfo
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- CN107802625A CN107802625A CN201610811651.8A CN201610811651A CN107802625A CN 107802625 A CN107802625 A CN 107802625A CN 201610811651 A CN201610811651 A CN 201610811651A CN 107802625 A CN107802625 A CN 107802625A
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- Prior art keywords
- pharmaceutical composition
- pioglitazone
- cis
- group
- lps
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 64
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims abstract description 234
- 229960005095 pioglitazone Drugs 0.000 claims abstract description 117
- PJANXHGTPQOBST-QXMHVHEDSA-N Cistacarpin Natural products C=1C=CC=CC=1/C=C\C1=CC=CC=C1 PJANXHGTPQOBST-QXMHVHEDSA-N 0.000 claims abstract description 86
- 239000000284 extract Substances 0.000 claims abstract description 78
- 229930182470 glycoside Natural products 0.000 claims abstract description 61
- -1 cis-stilbene glycosides Chemical class 0.000 claims abstract description 58
- 235000018167 Reynoutria japonica Nutrition 0.000 claims abstract description 43
- 240000001341 Reynoutria japonica Species 0.000 claims abstract description 43
- 231100000753 hepatic injury Toxicity 0.000 claims abstract description 34
- 239000000463 material Substances 0.000 claims abstract description 19
- 239000000203 mixture Substances 0.000 claims abstract description 19
- 230000002265 prevention Effects 0.000 claims abstract description 13
- 230000003285 pharmacodynamic effect Effects 0.000 claims abstract description 5
- 239000003826 tablet Substances 0.000 claims description 15
- 239000002775 capsule Substances 0.000 claims description 8
- 150000002338 glycosides Chemical class 0.000 claims description 8
- 239000000853 adhesive Substances 0.000 claims description 5
- 230000001070 adhesive effect Effects 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 4
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 238000004040 coloring Methods 0.000 claims description 3
- 239000006184 cosolvent Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000007884 disintegrant Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 40
- 238000002360 preparation method Methods 0.000 abstract description 14
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 239000002158 endotoxin Substances 0.000 description 122
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- 238000012360 testing method Methods 0.000 description 20
- 229940079593 drug Drugs 0.000 description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 11
- 108090001005 Interleukin-6 Proteins 0.000 description 11
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- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 5
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 5
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
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- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
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- 210000001519 tissue Anatomy 0.000 description 4
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 3
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- 108010016731 PPAR gamma Proteins 0.000 description 3
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- 238000006243 chemical reaction Methods 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
- 238000004043 dyeing Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
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- 235000019698 starch Nutrition 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 241001289529 Fallopia multiflora Species 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 2
- 241000256856 Vespidae Species 0.000 description 2
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- 230000037005 anaesthesia Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
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- 239000000287 crude extract Substances 0.000 description 2
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- 239000003292 glue Substances 0.000 description 2
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- 238000007654 immersion Methods 0.000 description 2
- 230000008799 immune stress Effects 0.000 description 2
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- 150000002576 ketones Chemical class 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
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- 238000002156 mixing Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011122 softwood Substances 0.000 description 2
- PJANXHGTPQOBST-UHFFFAOYSA-N trans-Stilbene Natural products C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 235000020985 whole grains Nutrition 0.000 description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- 102000005869 Activating Transcription Factors Human genes 0.000 description 1
- 108010005254 Activating Transcription Factors Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 1
- 244000292697 Polygonum aviculare Species 0.000 description 1
- 235000006386 Polygonum aviculare Nutrition 0.000 description 1
- 244000153955 Reynoutria sachalinensis Species 0.000 description 1
- 235000003202 Reynoutria sachalinensis Nutrition 0.000 description 1
- 235000008081 Rheum officinale Nutrition 0.000 description 1
- 240000004980 Rheum officinale Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 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
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
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- 238000012544 monitoring process Methods 0.000 description 1
- 102000006255 nuclear receptors Human genes 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
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- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 238000011105 stabilization Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
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Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/704—Polygonum, e.g. knotweed
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
This application provides a kind of pharmaceutical composition, described pharmaceutical composition includes Pioglitazone and radix-polygoni multiflori extract and pharmaceutically acceptable auxiliary material；Wherein, the weight ratio of the Pioglitazone and the radix-polygoni multiflori extract is 1:1400‑5600.Present invention also provides a kind of pharmaceutical composition, described pharmaceutical composition includes Pioglitazone and cis-stilbene glycosides and pharmaceutically acceptable auxiliary material；Wherein, the weight ratio of the Pioglitazone and cis-stilbene glycosides is 1:30‑120.Present invention also provides application of the described pharmaceutical composition in the pharmaceutical composition for preparing the prevention fleece-flower root and its preparation and compound cause hepatic injury.Present invention also provides application of the described pharmaceutical composition in preparing Chinese medicine and its preparation of the prevention using cis-stilbene glycosides as main pharmacodynamics composition and causing the pharmaceutical composition of hepatic injury.
Description
Technical field
The application relates to, but are not limited to a kind of pharmaceutical composition and its application.Specifically, the application is related to a kind of be used in advance
The Chinese medicine and its preparation of the anti-fleece-flower root or cis-stilbene glycosides cause pharmaceutical composition and its application of hepatic injury.
Background technology
The fleece-flower root is polygonum multiflorum thunb Polygonum multiflorum Thunb. root tuber, is mended for famous tradition
Beneficial class Chinese medicine, it is clinical conventional Chinese medicine and health food.China's most area is especially southern among the people often to take the fleece-flower root
The custom of health care, China also has more than 700 to plant Chinese patent drugs in addition and health food contains the fleece-flower root, and some fleece-flower root products are such as
Market is also in great demand very much abroad by Shou Wu Pian, Shen-Min etc., and crowd's radix that the fleece-flower root is taken in home and abroad is huge.So
And recent year, the outer report substantial increase about fleece-flower root adverse reaction, hepatic lesion event takes place frequently, in addition have liver transfer operation,
The report of hepatic failure.The relevant fleece-flower root cases of liver damage of the document report such as China and South Korea, Japan, Singapore, Britain is up to 180
Remaining example.The adverse reaction of the relevant fleece-flower root and its preparation that national adverse reaction center receives is reported nearly ten thousand (based on hepatic lesion)
Part, the hepatic lesion of the preparation containing the tuber of multiflower knotweed such as Radix Polygoni Multiflori, RADIX POLYGONI MULTIFLORI PREPARATA and Xinkang Capsules, fleece-flower root long-life piece, YANGXUE SHENGFA JIAONANG is bad
Reaction ranking in national adverse reaction monitoring system database ranks forefront and rapid development.
However, up to the present, it there is no dedicated for the effective of hepatic injury caused by the Chinese medicine and its preparation of the prevention fleece-flower root
Medicine.
The content of the invention
This application provides a kind of pharmaceutical composition, described pharmaceutical composition include Pioglitazone and radix-polygoni multiflori extract,
And pharmaceutically acceptable auxiliary material；Wherein, the weight ratio of the Pioglitazone and the radix-polygoni multiflori extract is 1:1400-
5600.In preferred embodiments, the weight ratio of the Pioglitazone and the radix-polygoni multiflori extract can be 1:1400-
4300.In preferred embodiments, the weight ratio of the Pioglitazone and the radix-polygoni multiflori extract can be 1:2000.
Present invention also provides a kind of pharmaceutical composition, described pharmaceutical composition includes Pioglitazone and cis-stilbene
Glycosides and pharmaceutically acceptable auxiliary material；Wherein, the weight ratio of the Pioglitazone and cis-stilbene glycosides is 1:30-
120.In preferred embodiments, the weight ratio of the Pioglitazone and cis-stilbene glycosides can be 1:50.Preferred
Embodiment in, cis-stilbene glycosides can refer to using cis-stilbene glycosides as main pharmacodynamics composition or second containing hexichol
The Chinese medical extract of alkene glycosides.
In the preferred embodiment of described pharmaceutical composition, the pharmaceutically acceptable auxiliary material may include stabilization
One or more in agent, antioxidant, colouring agent, diluent, excipient, adhesive, disintegrant, cosolvent, lubricant.
In the preferred embodiment of described pharmaceutical composition, described pharmaceutical composition can be formed as tablet, granule, pill, glue
Capsule or oral liquid.
Present invention also provides described pharmaceutical composition in preparing the prevention fleece-flower root and causing the pharmaceutical composition of hepatic injury
Using.
Present invention also provides described pharmaceutical composition to prepare the medicine group of prevention cis-stilbene glycosides cause hepatic injury
Application in compound.
This application provides a kind of pharmaceutical composition and its application.The pharmaceutical composition can be effective for preventing the fleece-flower root
Chinese medicine and its preparation cause hepatic injury, Chinese medicine to the fleece-flower root and its preparation cause the preventing and treating of hepatic injury to have important meaning.
Inventor studies one of material base for finding that cis-stilbene glycosides is fleece-flower root cause hepatic injury, zoopery knot
Fruit shows that cis-stilbene glycosides can produce hepatic injury under the conditions of immunological stress.Stibene-glucoside for the fleece-flower root it is main into
Point, the existence form of Stibene-glucoside has two kinds, respectively trans stilbene glycosides and cis-stilbene glycosides.Cis hexichol second
Alkene glycosides is to be transformed by trans stilbene glycosides by light irradiation, and conversion ratio is up to more than 90% in the sunlight, while what is first
The black content through solar radiation cis-stilbene glycosides also can be raised significantly.That is current people are utilizing fleece-flower root etc.
Chinese medicine containing Stibene-glucoside or while treat disease as principle active component using Stibene-glucoside, will be inevitable
Cis-stilbene glycosides is introduced, so as to cause hepatic injury.
Peroxisome proliferator-activated receptor (peroxisome proliferator-activated receptors,
PPARs), it is a kind of transcription factor by ligand activation, belongs to II type nuclear receptor superfamily members.PPARs includes 3 hypotypes, i.e.,
PPARα、PPARγ、PPARδ.Recent study finds that PPARs effect is very extensive, in addition to lipid-metabolism, glycometabolism is related to,
Also played a significant role in cell proliferation and differentiation, apoptosis, wound healing and inflammation regulation process.Pioglitazone category thiazolidine two
Ketone compounds, it is high selectivity PPAR gamma agonists.Numerous in vivo and in vitro find that PPAR gamma agonist Pioglitazones have
Obvious antiinflammatory action, regulate and control NF- κ B, signal transduction and activating transcription factor, transforming growth factor-β1 by activating PPAR γ approach
Deng signal path, suppress the expression and release of the cell factors such as IL-1, IL-6, TNF-α, reduce inflammation reaction and tissue damage journey
Degree.
Present inventor has found on the basis of practical experience after numerous studies are analyzed, Pioglitazone with may
Cause the cis-stilbene glycosides of hepatic injury to be used cooperatively, can effectively prevent possible hepatic injury.
Therefore, this application provides a kind of pharmaceutical composition, described pharmaceutical composition includes Pioglitazone and the fleece-flower root carries
Take thing and pharmaceutically acceptable auxiliary material；Wherein, the weight ratio of the Pioglitazone and the radix-polygoni multiflori extract is 1:
1400-5600。
In presently filed embodiment, the weight ratio of the Pioglitazone and the radix-polygoni multiflori extract can be 1:
1400-4300.Alternatively, the weight of the Pioglitazone and radix-polygoni multiflori extract ratio can be 1:1400、1:2000、1:
2800、1:4000、1:4300、1:5600.Preferably, the weight of the Pioglitazone and radix-polygoni multiflori extract ratio can be
1:1400、1:2000、1:2800、1:4000、1:4300；Most preferably, the Pioglitazone and the radix-polygoni multiflori extract
Weight ratio can be 1:1400、1:2000、1:4300.
Wherein, the radix-polygoni multiflori extract is in the market or the extract extracted according to methods known in the art.For example,
After material of getting it filled immersion 30min, add 10 times of amount water heating extractings 3 times, each 1.5h, merge extract solution and be concentrated under reduced pressure, be dried in vacuo
Obtain crude extract (medicinal extract rate is 24%).
Present invention also provides a kind of pharmaceutical composition, described pharmaceutical composition includes Pioglitazone and cis-stilbene
Glycosides and pharmaceutically acceptable auxiliary material；Wherein, the weight ratio of the Pioglitazone and cis-stilbene glycosides is 1:30-
400。
In presently filed embodiment, the weight ratio of the Pioglitazone and cis-stilbene glycosides can be 1:30-
120；Alternatively, the weight of Pioglitazone and cis-stilbene glycosides ratio can be 1:30、1:50、1:60、1:100、1:120、
1:200、1:400.Preferably, the weight ratio of the Pioglitazone and cis-stilbene glycosides can be 1:30、1:50、1:60、
1:100、1:120.Most preferably, the weight ratio of the Pioglitazone and cis-stilbene glycosides can be 1:30、1:50、1:
100。
In this application, cis-stilbene glycosides can be in the extract from Chinese medicines such as the fleece-flower root, giant knotweed, rheum officinales
Cis-stilbene glycosides.Alternatively, cis-stilbene glycosides can come from radix-polygoni multiflori extract.
In this application, the pharmaceutically acceptable auxiliary material can include it is well known by persons skilled in the art any one
Auxiliary material, specifically, those skilled in the art can be selected according to actual conditions.Alternatively, it is described pharmaceutically acceptable
Auxiliary material can include stabilizer, antioxidant, colouring agent, diluent, excipient, adhesive, disintegrant, cosolvent, lubricant
One or more in.
In presently filed embodiment, pharmaceutically acceptable auxiliary material can include starch, dextrin, sucrose, lactose, micro-
The one or more of crystalline cellulose, inorganic salts, citric acid, gelatine size, sodium carboxymethylcellulose etc..
In presently filed embodiment, described pharmaceutical composition can also include other active ingredients, the active ingredient
Species and dosage can be selected according to the situation of the disease of actual therapeutic.That is, the pharmaceutical composition of the application can be with
Be it is existing containing the medicine of radix-polygoni multiflori extract or cis-stilbene glycosides on the basis of add a certain proportion of pyrrole lattice row
The pharmaceutical composition that ketone is obtained.The pharmaceutical composition can not only be realized containing radix-polygoni multiflori extract or cis-stilbene glycosides
The effect of drug therapy, moreover it is possible to avoid hepatic injury caused by radix-polygoni multiflori extract or cis-stilbene glycosides.
In presently filed embodiment, described pharmaceutical composition can be prepared into suitable patient and take according to being actually needed
Any pharmacy on acceptable appropriate formulation.Alternatively, described pharmaceutical composition can be formed as tablet, granule,
Pill, capsule or oral liquid.
In presently filed embodiment, the conventional method of this area can be used by the foregoing pharmaceutical composition of the application
Be prepared into acceptable appropriate formulation in pharmacy, for example, including but not limited to conventional tablet, sustained-release tablet, Dospan,
Sublingual lozenge, oral quick disintegrating tablet, dispersible tablet, enteric coatel tablets, granule, pill, conventional capsule, soft capsule, capsulae enterosolubilis, sustained release glue
Capsule, controlled release capsule, oral liquid.Wherein, optional common formulations are tablet or capsule.
The pharmaceutical composition of the application can be administered in a unit, and method of administration can be Parenteral administration, alternatively
It is administered orally.
The dosage of the pharmaceutical composition of the application and the fleece-flower root and the Chinese medicine and its preparation of the glycosides containing cis-stilbene
Script dosage it is consistent, therefore the therapeutic dose excursion of the composition of medicine is little.In general, the group of the application
The dosage of Pharmaceutical Compositions in composite medicine is that well known to a person skilled in the art can be according to last in pharmaceutical composition
Contained actual drug quantity, is subject to appropriate adjustment, to reach the requirement of its therapeutically effective amount, realizes the application in preparation
Prevention purpose.
Present invention also provides pharmaceutical composition as described above in the prevention fleece-flower root causes the pharmaceutical composition of hepatic injury
Application.
The medicine of hepatic injury is caused in prevention cis-stilbene glycosides present invention also provides pharmaceutical composition as described above
Application in composition.
The pharmaceutical composition of the application causes hepatic injury or using cis-stilbene glycosides as main pharmacodynamics in the prevention fleece-flower root
The Chinese medicine and its preparation of composition cause have the effect of fine in hepatic injury.
Brief description of the drawings
Accompanying drawing is used for providing further understanding technical scheme, and a part for constitution instruction, with this
The embodiment of application is used for the technical scheme for explaining the application together, does not form the limitation to technical scheme.
Fig. 1 is the liver HE colored graphs of normal rat group in testing example 1 (for Fig. 2-Fig. 6 control)；
Fig. 2 is the liver HE colored graphs of LPS model groups in testing example 1 (for Fig. 7 control)；
Fig. 3 is Pioglitazone group in testing example 1 (500 μ g/kg) liver HE colored graphs；
Fig. 4 is the liver HE colored graphs of independent radix-polygoni multiflori extract powder group (2.16g crude drugs/kg) in testing example 1
(for Fig. 8-Fig. 9 control)；
Fig. 5 is the liver HE colored graphs of composition of medicine group in testing example 1；
Fig. 6 is the liver HE colored graphs that LPS combines Pioglitazone group (500 μ g/kg) in testing example 1；
Fig. 7 is the liver HE dyeing that LPS combines radix-polygoni multiflori extract powder group (2.16g crude drugs/kg) in testing example 1
Figure；
Fig. 8 is the liver HE colored graphs that LPS combines composition of medicine group in testing example 1；
Fig. 9 be in testing example 1 LPS combine radix-polygoni multiflori extract powder joint Pioglitazone group (2.16g crude drugs/kg,
500 μ g/kg) liver HE colored graphs；
Figure 10 is the liver HE colored graphs of normal rat group in testing example 2 (for Figure 11-Figure 15 control)；
Figure 11 is the liver HE colored graphs of LPS model groups in testing example 2 (for Figure 16 control)；
Figure 12 is Pioglitazone group in testing example 2 (500 μ g/kg) liver HE colored graphs；
Figure 13 is the liver HE colored graphs of independent cis-stilbene glycosides group (50mg/kg) in testing example 2 (for figure
17- Figure 18 control)；
Figure 14 is the liver HE colored graphs of composition of medicine group in testing example 2；
Figure 15 is the liver HE colored graphs that LPS combines Pioglitazone group (500 μ g/kg) in testing example 2；
Figure 16 is the liver HE colored graphs that LPS combines cis-stilbene glycosides group (50mg/kg) in testing example 2；
Figure 17 is the liver HE colored graphs that LPS combines composition of medicine group in testing example 2；
Figure 18 is that LPS combines cis-stilbene glycosides joint Pioglitazone group (50mg/kg, 500 μ g/ in testing example 2
Kg liver HE colored graphs).
Embodiment
Embodiments of the present invention are described below by embodiment, for it will be appreciated by the person skilled in the art that
These specific embodiments only indicate that to the purpose for reaching the application and the implementation technical scheme selected, are not to technical side
The limitation of case.It is obvious with reference to improvement of the prior art to technical scheme according to teachings of the present application, belongs to this
Apply for the scope of protection.
Embodiment 1
Prepare the tablet of the pharmaceutical composition comprising Pioglitazone and radix-polygoni multiflori extract
(1) percentage by weight of the Pioglitazone in pharmaceutical composition and radix-polygoni multiflori extract can be：
Pioglitazone：Radix-polygoni multiflori extract=1:1400
Pioglitazone：Radix-polygoni multiflori extract=1:2000
Pioglitazone：Radix-polygoni multiflori extract=1:2800
Pioglitazone：Radix-polygoni multiflori extract=1:4000
Pioglitazone：Radix-polygoni multiflori extract=1:4300
Pioglitazone：Radix-polygoni multiflori extract=1:5600
Wherein, the radix-polygoni multiflori extract is in the market or the extract extracted according to methods known in the art.For example,
After material of getting it filled immersion 30min, add 10 times of amount water heating extractings 3 times, each 1.5h, merge extract solution and be concentrated under reduced pressure, be dried in vacuo
Obtain crude extract (medicinal extract rate is 24%).
(2) Pioglitazone is chosen：Radix-polygoni multiflori extract=1:1400、1:2000、1:2800、1:4000、1:4300、1:
5600 proportioning, form tablet formulation in table 1 below and prepare corresponding tablet：
Table 1
The preparation method of tablet：
1. take the Pioglitazone (being purchased from HaiNan Kangzhi Pharmaceutical Co., Ltd) and radix-polygoni multiflori extract of formula ratio in table 1
Powder (from extracted extract rate be 24%) respectively cross 100 mesh sieves after by isometric incremental method mix it is standby；
2. according to the tablet formulation of table 1, the other auxiliary in addition to 5% PVP K-30 and magnesium stearate of formula ratio is weighed
Material mixes standby；
3. the mixture of above-mentioned two step is mixed, addition suitable amount of adhesive 5% PVP K-30 mixing softwood processed, 24
Mesh sieve is pelletized, 40-45 DEG C of drying；
4. pass through 20 mesh sieve whole grains；
5. dry particl adds appropriate magnesium stearate and mixed；
6. tabletting after assay, tablet is made.
Wherein, microcrystalline cellulose, pregelatinized starch, carboxyrnethyl starch sodium, 5% PVP K-30 and magnesium stearate are commercially available
Product, and it is purchased from Anhui Shanhe Medical Accessary Material Co., Ltd..
Embodiment 2
Preparing the tablet comprising Pioglitazone and the pharmaceutical composition of cis-stilbene glycosides, (cis-stilbene glycosides comes from
Radix-polygoni multiflori extract, account for 5 ‰)
(1) percentage by weight of the Pioglitazone in pharmaceutical composition and cis-stilbene glycosides can be：
Pioglitazone：Cis-stilbene glycosides=1:30
Pioglitazone：Cis-stilbene glycosides=1:50
Pioglitazone：Cis-stilbene glycosides=1:60
Pioglitazone：Cis-stilbene glycosides=1:100
Pioglitazone：Cis-stilbene glycosides=1:120
(2) Pioglitazone is chosen：Cis-stilbene glycosides=1:30、1:50、1:60、1:100、1:120 proportioning, composition
Tablet formulation and corresponding tablet is prepared in table 2 below：
Table 2.
The preparation method of tablet：
1. take the Pioglitazone (being purchased from HaiNan Kangzhi Pharmaceutical Co., Ltd) of formula ratio and radix-polygoni multiflori extract (commercially available
Or according to methods known in the art extract extract) respectively cross 100 mesh sieves after by isometric incremental method mix it is standby；
2. according to the tablet formulation of table 2, the other auxiliary in addition to 5% PVP K-30 and magnesium stearate of formula ratio is weighed
Material mixes standby；
3. the mixture of above-mentioned two step is mixed, addition suitable amount of adhesive 5% PVP K-30 mixing softwood processed, 24
Mesh sieve is pelletized, 40-45 DEG C of drying；
4. pass through 20 mesh sieve whole grains；
5. dry particl adds appropriate magnesium stearate and mixed；
6. tabletting after assay, tablet is made.
Wherein, microcrystalline cellulose, pregelatinized starch, carboxyrnethyl starch sodium, 5% PVP K-30 and magnesium stearate are commercially available
Product, and it is purchased from Anhui Shanhe Medical Accessary Material Co., Ltd..
Testing example 1
The pharmacological activity experiment of pharmaceutical composition comprising Pioglitazone and radix-polygoni multiflori extract
1. the prevention effect of hepatic injury is caused to the fleece-flower root：
Experimental animal：SD rats, 66, male, cleaning grade, the weight of animals 160-200g.
Experiment packet：
Normal rat group (6)；
(this seminar early-stage Study finds that the fleece-flower root and cis-stilbene glycosides are led to LPS groups (2.8mg/kg) (9)
The hepatic injury of cause is diathesis hepatic injury, therefore this experiment uses endotoxin diathesis model, that is, animal is originally in after giving LPS
In immunological stress state, and hepatic injury will not be now produced, simply immune factor significantly raises, and then gives the fleece-flower root and cis
After Stibene-glucoside, animal produces diathesis hepatic injury.)；
Independent radix-polygoni multiflori extract powder group (2.16g crude drugs/kg) (6)；
Independent Pioglitazone group (500 μ g/kg) (6)；
1 in table 1:Prescription drug group made of 2000 (the μ g/kg+ fleece-flowers root 2.16g crude drugs of Pioglitazone 250/kg) (6
Only)；
LPS joint Pioglitazone groups (500 μ g/kg) (6)；
LPS joint radix-polygoni multiflori extract powder groups (2.16g crude drugs/kg) (9)；
Pioglitazone joint LPS joint radix-polygoni multiflori extract powder groups (500 μ g/kg, 2.16g crude drug/kg) (9)；
1 in LPS association lists 1:Prescription drug group made of 2000 (the μ g/kg+ fleece-flower root 2.16g crude drugs of Pioglitazone 250/
Kg) (9).
Independent Pioglitazone group, LPS joints Pioglitazone, Pioglitazone joint LPS joint radix-polygoni multiflori extract powder groups
Continuous three days gavage Pioglitazones, independent radix-polygoni multiflori extract powder group, LPS joint radix-polygoni multiflori extract powder group fill on the 3rd day
Stomach radix-polygoni multiflori extract, 1 in table 1:1 in prescription drug group, LPS association lists 1 made of 2000:Prescription drug group made of 2000
1 in gavage table 1:Prescription drug made of 2000,3h after administration, LPS groups, LPS joint Pioglitazones group, the LPS joint fleece-flowers root
1 in extract powder group, Pioglitazone joint LPS joint radix-polygoni multiflori extract powder group, LPS association lists 1:Match somebody with somebody made of 2000
7h after square medicine group tail vein injection LPS, tail vein injection LPS, using 1% yellow Jackets (50mg/kg) by rat anesthesia,
Inferior caval vein takes blood and gathers hepatic tissue sample.
Wherein, radix-polygoni multiflori extract powder is purchased from Beijing green field pharmaceutcal corporation, Ltd, and Pioglitazone is purchased from Hainan Kang Zhi medicines
Industry limited company.Lipopolysaccharides (lipopolysaccharide, LPS) is purchased from Sigma companies.
Experimental result is referring to Fig. 1-9.
From Fig. 1-9 as can be seen that liver HE dyeing pathological examinations show that compared with Normal group (Fig. 1), individually what is first
1 in black extract powder group (Fig. 4), Pioglitazone group (Fig. 3), table 1:Prescription drug group (Fig. 5), LPS joints made of 2000
1 in Pioglitazone (Fig. 6) and LPS association lists 1:The hepatic tissue of prescription drug group (Fig. 8) is without notable pathology made of 2000
Change；There is slight inflammatory cell infiltration LPS groups (Fig. 2) portal area；LPS joint radix-polygoni multiflori extract powder groups (Fig. 7) are visible
Central vein expansion, inner membrance come off, and there are a large amount of inflammatory cell infiltrations swelling of liver cell, necrosis, portal area；Pioglitazone is combined
LPS joint radix-polygoni multiflori extract powder groups (Fig. 9) are visible to be obviously improved swelling of liver cell, necrosis phenomena, reduces inflammatory cell leaching
Profit.
Moreover, LPS combines fleece-flower root group ALT, AST apparently higher than other groups, but Pioglitazone joint LPS combines the fleece-flower root
Extract powder group is substantially reduced to close to normal level with damage group than ALT, AST.Independent Pioglitazone group, fleece-flower root extraction
1 in thing powder group, table 1:1 in prescription drug group, LPS joint Pioglitazone groups and LPS association lists 1 made of 2000:2000 systems
Into prescription drug group in the serum glutamic pyruvic transminase (ALT), glutamic-oxalacetic transaminease (AST) and normal group and the LPS groups that measure than
No significant difference, and LPS joint Pioglitazone groups combine LPS joint radix-polygoni multiflori extract powder group curative effect phases with Pioglitazone
When the results are shown in Table 3, (data are represented with mean ± standard deviation (x ± s), statistical analysis are done with the softwares of SPSS 13.0, with p<
0.05 represents that both difference has significant).As can be seen from Table 3,1 in LPS association lists 1:Magistral medicines made of 2000
Thing group combines LPS joint fleece-flower root group therapeutic equivalences with Pioglitazone, and ALT, AST illustrate 1 in table 1 close to normal level:2000
Manufactured prescription drug Pioglitazone and the fleece-flower root can effectively prevent the hepatic injury caused by the fleece-flower root.
Table 3
A. 1 in normal group B.LPS groups C. radix-polygoni multiflori extracts powder group D. Pioglitazone group E. tables 1:Match somebody with somebody made of 2000
Square medicine group F.LPS joint radix-polygoni multiflori extract powder groups G.LPS joint Pioglitazone group H. Pioglitazones group joint LPS joints
1 in radix-polygoni multiflori extract powder group I.LPS association lists 1:Prescription drug group made of 2000
a：P<0.05, compared with LPS groups；b：P<0.05, compared with independent radix-polygoni multiflori extract powder group；c：P<0.05,
Compared with combining radix-polygoni multiflori extract powder group with LPS
Meanwhile TNF-α, IL-6 and the IFN-γ and normal group measured in LPS groups is than significantly rise, the LPS joint fleece-flowers root
Extract powder group TNF-α, IL-6 and IFN-γ are apparently higher than other groups.Pioglitazone joint LPS joint radix-polygoni multiflori extracts
Powder group TNF-α, IL-6 and IFN-γ and damage group ratio significantly reduce, 1 in LPS association lists 1:Prescription drug group made of 2000
TNF-α, IL-6 and IFN-γ expression are suitable with Pioglitazone joint LPS joint radix-polygoni multiflori extract powder groups, the results are shown in Table 4
(data are with mean ± standard deviationRepresent, statistical analysis is done with the softwares of SPSS 13.0, with p<0.05 represents both
Difference has significant).As can be seen from Table 4, Pioglitazone joint LPS joints radix-polygoni multiflori extract powder group TNF-α,
IL-6 and IFN-γ significantly reduce with damage group ratio, illustrate that Pioglitazone can suppress the secretion of inflammatory factor, alleviate hepatic injury,
Simultaneously 1 in LPS association lists 1:Prescription drug group made of 2000 combines LPS joint radix-polygoni multiflori extract powder groups with Pioglitazone
Inflammatory factor change level is suitable, illustrates 1 in table 1:Prescription drug Pioglitazone made of 2000 and the fleece-flower root can effectively prevent
Hepatic injury caused by the fleece-flower root.
Table 4
A. 1 in normal group B.LPS groups C. radix-polygoni multiflori extracts powder group D. Pioglitazone group E. tables 1:Match somebody with somebody made of 2000
Square medicine group F.LPS joint radix-polygoni multiflori extract powder groups G.LPS joint Pioglitazone group H. Pioglitazones group joint LPS joints
1 in radix-polygoni multiflori extract powder group I.LPS association lists 1:Prescription drug group made of 2000
a：P<0.05, compared with normal group；b：P<0.05, compared with LPS groups；c：P<0.05, combine the fleece-flower root with LPS and carry
Thing powder group is taken to compare
Testing example 2
The pharmacological activity experiment of pharmaceutical composition comprising Pioglitazone and cis-stilbene glycosides
Cis-stilbene glycosides causes the prevention effect of hepatic injury：
Experimental animal：SD rats, 66, male, cleaning grade, the weight of animals 160-200g.
Experiment packet：Normal rat group (6)；
LPS groups (2.8mg/kg) (9)；
Cis-stilbene glycosides group (50mg/kg) (6)；
Pioglitazone group (500 μ g/kg) (6)；
1 in table 2:Prescription drug group made of 50 (the μ g/kg+ cis-stilbenes glycosides 50mg/kg of Pioglitazone 250) (6
Only)；
LPS joint Pioglitazone groups (500 μ g/kg) (6)；
LPS joint cis-stilbene glycosides groups (50mg/kg) (9)；
Pioglitazone joint LPS joint cis-stilbene glycosides groups (2.8mg/kg, 50mg/kg) (9)；
1 in LPS association lists 2:(the μ g/kg+ cis-stilbene glycosides 50mg/ of Pioglitazone 250 of prescription drug group made of 50
Kg) (9).
Independent Pioglitazone group, LPS joints Pioglitazone, Pioglitazone joint LPS joint cis-stilbene glycosides groups connect
Continue three days gavage Pioglitazones, independent cis-stilbene glycosides group, LPS joint cis-stilbene glycosides the 3rd day gavage of group are cis
Stibene-glucoside solution, 1 in table 2:1 in prescription drug group, LPS association lists 2 made of 50:Prescription drug group gavage made of 50
1 in table 2:Prescription drug made of 50,3h after administration, LPS groups, LPS joint Pioglitazones group, LPS joint cis-stilbenes
1 in glycosides group, Pioglitazone joint LPS joint cis-stilbene glycosides group, LPS association lists 2:Prescription drug group tail is quiet made of 50
7h after arteries and veins injection LPS, tail vein injection LPS, blood is taken using 1% yellow Jackets (50mg/kg) by rat anesthesia, inferior caval vein
And gather hepatic tissue sample.
Wherein, Stibene-glucoside is purchased from Chengdu Puffy moral Bioisystech Co., Ltd, and Pioglitazone is purchased from Hainan Kang Zhi medicines
Industry limited company.Lipopolysaccharides (lipopolysaccharide, LPS) is purchased from Sigma companies.
Experimental result：
Liver HE dyeing pathological examinations show, compared with Normal group (Figure 10), independent cis-stilbene glycosides group (figure
13), 1 in Pioglitazone group (Figure 12), table 2:Prescription drug group (Figure 14), LPS joint Pioglitazone groups (Figure 15) made of 50
And 1 in LPS association lists 2:The hepatic tissue of prescription drug group (Figure 17) is without notable pathological change made of 50；LPS groups (Figure 11)
There is slight inflammatory cell infiltration portal area；The visible central vein expansion of LPS joint cis-stilbene glycosides groups (Figure 16), inner membrance
Come off, swelling of liver cell, necrosis, portal area there are a large amount of inflammatory cell infiltrations；Pioglitazone joint LPS joint cis-stilbenes
Glycosides group (Figure 18) is visible to be obviously improved swelling of liver cell, necrosis phenomena, reduces inflammatory cell infiltration.
Moreover, LPS combines fleece-flower root group ALT, AST apparently higher than other groups, but Pioglitazone joint LPS combines cis two
Styrene glycosides group is substantially reduced to close to normal level with damage group than ALT, AST.Independent Pioglitazone group, cis-stilbene
1 in glycosides group, table 2:1 in prescription drug group, LPS joint Pioglitazone groups and LPS association lists 2 made of 50:It is formulated made of 50
Serum glutamic pyruvic transminase (ALT), glutamic-oxalacetic transaminease (AST) and the normal group and LPS groups measured in medicine group is more obvious than nothing poor
It is different, and 1 in LPS association lists 2:Prescription drug group made of 50 is combined LPS joint cis-stilbene glycosides groups with Pioglitazone and treated
Effect is suitable, and the results are shown in Table 5, (data are with mean ± standard deviationRepresent, statistical analysis is done with SPSS13.0 softwares, with p
<0.05 represents that both difference has significant).As can be seen from Table 5,1 in LPS association lists 2:Prescription drug made of 50
Group combines LPS joint cis-stilbene glycosides group therapeutic equivalences with Pioglitazone, and ALT, AST illustrate in table 2 close to normal level
1:Prescription drug Pioglitazone made of 50 and cis-stilbene glycosides can effectively prevent caused by cis-stilbene glycosides group
Hepatic injury.
Table 5.
A. 1 in normal group B.LPS groups C. Pioglitazones group D. cis-stilbene glycosides group E. tables 2:Magistral medicines made of 50
Thing group F.LPS joint cis-stilbene glycosides group G.LPS joint Pioglitazone group H. Pioglitazones group joint LPS joints cis two
1 in styrene glycosides group I.LPS association lists 2:Prescription drug group made of 50
a：P<0.05, compared with LPS groups；b：P<0.05, compared with independent cis-stilbene glycosides group；c：P<0.05, with
LPS joint cis-stilbene glycosides groups compare
Meanwhile TNF-α, IL-6 and the IFN-γ and normal group measured in LPS groups is than significantly rise, LPS joints cis two
Styrene glycosides group TNF-α, IL-6 and IFN-γ are apparently higher than other groups.Pioglitazone joint LPS joint cis-stilbene glycosides
Group TNF-α, IL-6 and IFN-γ and damage group ratio significantly reduce, 1 in LPS association lists 2:Prescription drug group TNF-α made of 50,
IL-6 and IFN-γ expression are suitable with Pioglitazone joint LPS joint cis-stilbene glycosides groups, and the results are shown in Table 6, (data are with equal
Number ± standard deviation (x ± s) represents, statistical analysis is done with the softwares of SPSS 13.0, with p<0.05 represents that both difference has significantly
Property meaning).As can be seen from Table 6, Pioglitazone joint LPS joints cis-stilbene glycosides group TNF-α, IL-6 and IFN-γ with
Damage group ratio significantly reduces, and illustrates that Pioglitazone can suppress the secretion of inflammatory factor, alleviates hepatic injury, while LPS association lists 2
In 1:Prescription drug group made of 50 combines LPS joint cis-stilbene glycosides group inflammatory factor change level phases with Pioglitazone
When illustrating 1 in table 2:Prescription drug Pioglitazone made of 50 and cis-stilbene glycosides can effectively prevent caused by the fleece-flower root
Hepatic injury.
Table 6
A. 1 in normal group B.LPS groups C. Pioglitazones group D. cis-stilbene glycosides group E. tables 2:Magistral medicines made of 50
Thing group F.LPS joint cis-stilbene glycosides group G.LPS joint Pioglitazone group H. Pioglitazones group joint LPS joints cis two
1 in styrene glycosides group I.LPS association lists 2:Prescription drug group made of 50
a：P<0.05, compared with normal group；b：P<0.05, compared with LPS groups；c：P<0.05, cis hexichol is combined with LPS
Ethene glycosides group compares
Above example shows, 1 in table 1:1 in prescription drug made of 2000 and table 2:Pyrrole in prescription drug made of 50
Lattice row ketone can effectively suppress the secretion of inflammatory factor, and Pioglitazone is with the fleece-flower root or using cis-stilbene glycosides as main pharmacodynamics
The combination of the Chinese medical extract of composition can effectively prevent caused by the Chinese medicine and its preparation of the fleece-flower root and the glycosides containing cis-stilbene
Hepatic injury, reduce the risk that hepatic injury occurs, ensure the normal physiological activity of liver.
The application includes but is not limited to above example, it is every carried out under the principle of the application spirit any equally replace
Generation or local improvement, all will be regarded as within the protection domain of the application.
Claims (10)
1. a kind of pharmaceutical composition, described pharmaceutical composition includes Pioglitazone and radix-polygoni multiflori extract and can pharmaceutically connect
The auxiliary material received；Wherein, the weight ratio of the Pioglitazone and the radix-polygoni multiflori extract is 1:1400-5600.
2. pharmaceutical composition according to claim 1, wherein, the weight of the Pioglitazone and the radix-polygoni multiflori extract
Than for 1:1400-4300.
3. pharmaceutical composition according to claim 1, wherein, the weight of the Pioglitazone and the radix-polygoni multiflori extract
Than for 1:2000.
4. a kind of pharmaceutical composition, described pharmaceutical composition includes Pioglitazone and cis-stilbene glycosides and pharmaceutically may be used
The auxiliary material of receiving；Wherein, the weight ratio of the Pioglitazone and cis-stilbene glycosides is 1:30-120.
5. pharmaceutical composition according to claim 4, wherein, the weight ratio of the Pioglitazone and cis-stilbene glycosides
For 1:50.
6. pharmaceutical composition according to claim 4, wherein, cis-stilbene glycosides refer to using cis-stilbene glycosides as
Main pharmacodynamics composition or the Chinese medical extract containing Stibene-glucoside.
7. according to the pharmaceutical composition any one of claim 1-6, wherein, the pharmaceutically acceptable auxiliary material includes
One kind or more in stabilizer, antioxidant, colouring agent, diluent, excipient, adhesive, disintegrant, cosolvent, lubricant
Kind.
8. according to the pharmaceutical composition any one of claim 1-6, wherein, described pharmaceutical composition be formed as tablet,
Granule, pill, capsule or oral liquid.
9. the pharmaceutical composition any one of claim 1-6 is preparing the pharmaceutical composition of prevention fleece-flower root cause hepatic injury
In application.
10. the pharmaceutical composition any one of claim 1-6 is preparing the glycosides cause hepatic injury of prevention cis-stilbene
Application in pharmaceutical composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610811651.8A CN107802625A (en) | 2016-09-08 | 2016-09-08 | A kind of pharmaceutical composition and its application |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610811651.8A CN107802625A (en) | 2016-09-08 | 2016-09-08 | A kind of pharmaceutical composition and its application |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102462743A (en) * | 2010-11-16 | 2012-05-23 | 北京博远欣绿科技有限公司 | Chinese medicine composition with auxiliary protection action on chemical hepatic injury as well as preparation method and application thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102462743A (en) * | 2010-11-16 | 2012-05-23 | 北京博远欣绿科技有限公司 | Chinese medicine composition with auxiliary protection action on chemical hepatic injury as well as preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 贺兰芝 等: "吡格列酮对何首乌致大鼠特异质肝损伤的防治作用及机制初探", 《2016年第六届全国药物毒理学年会——论文集》 * |
| 贺兰芝 等: "吡格列酮对何首乌致大鼠特异质肝损伤的防治作用及机制初探", 《中国毒理学会中药与天然药物毒理专业委员会第一次（2016年）学术交流大会》 * |
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