CN107028954A - Ornithine aspartate is preparing the purposes in preventing and treating fatty liver medicament - Google Patents
Ornithine aspartate is preparing the purposes in preventing and treating fatty liver medicament Download PDFInfo
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- CN107028954A CN107028954A CN201510442089.1A CN201510442089A CN107028954A CN 107028954 A CN107028954 A CN 107028954A CN 201510442089 A CN201510442089 A CN 201510442089A CN 107028954 A CN107028954 A CN 107028954A
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- ornithine aspartate
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Abstract
The purposes in preventing and treating fatty liver medicament is being prepared the present invention relates to Ornithine aspartate.Characterized in that, described pharmaceutical composition is included：（a）Ornithine aspartate or its pharmaceutically acceptable salt；（b）Selected from following at least one active component or its officinal salt and pharmaceutical acceptable carrier：（1）Shellfish cholic acid difficult to understand；（2）Thiazolidinediones.Ornithine aspartate dosage is more much lower and more excellent than folk prescription medication effect after drug regimen than individually giving Ornithine aspartate after drug regimen of the present invention.The present invention reduces the dosage of Ornithine aspartate by drug regimen, and possibility is provided to develop further types of Ornithine aspartate preparation；Shellfish cholic acid or Thiazolidinediones consumption difficult to understand are seldom in drug regimen of the present invention simultaneously, after drug regimen, shellfish cholic acid or Thiazolidinediones dosage difficult to understand are also than clinically much lower, due to the reduction of its dosage, shellfish cholic acid difficult to understand or Thiazolidinediones side effect can be also reduced to a certain degree.
Description
Technical field
The purposes in preventing and treating fatty liver medicament is being prepared the present invention relates to Ornithine aspartate.
Background technology
Liver is glandula digestive maximum in human body, is responsible for substance in vivo energetic supersession, maintains the daily vital movement of the mankind.Liver
Lesion, including virus hepatitis, hepatic sclerosis, fatty liver, liver cancer etc. is a kind of great disease of common harmfulness, should be with
Based on active prevention.Hepatopathy species can be divided into viral liver disease and Non-viral liver disease according to pathogenesis：
Non-viral liver disease mainly includes following several：(1) AML, is due to that long-term heavy drinking (being addicted to drink) is caused
Hepar damnification disease；(2) medicine or poisonous substance hepatopathy, is by chemical toxicant (such as phosphorus, arsenic, carbon tetrachloride), medicine
Hepatitis or caused hepatic disease caused by thing or biotoxin；(3) NASH (NAFLD), refer to by
In the excessive hepatic disease of fat accumulation in liver cell caused by a variety of causes such as diabetes, the too high, overweight of blood fat, its
Including simple fatty liver, nonalcoholic fatty liver disease and its related liver cirrhosis, as fat and its associated metabolic syndrome is complete
The fashion trend of nodularization, NASH has turned into the important of the developed country such as America and Europe and China's areas of well-being chronic liver disease
The cause of disease, NASH can also influence other chronic liver diseases in addition to it can directly result in decompensated liver cirrhosis, hepatocellular carcinoma
Progress, and participate in the morbidity of diabetes B and atherosclerosis.
NAFLD pathogenesis not yet clearly, mainly there is following two hypothesis so far：1. peripheral insulin resistance increases lipid
Degraded, promotes free fatty (FFA) to be transported to liver, increases the beta oxidation of aliphatic acid, therefore causes oxidative stress；②
Exception in liver cell causes liver cell more susceptible to the damage from oxidative stress.
NAFLD treatment method is loses weight and drug therapy, and conventional medicine has (1) insulin sensitizer, such as thiophene
Oxazolidinedione class medicine, melbine etc.；(2) antioxidant, such as vitamin E, silymarin；(3) lipid-lowering medicine,
Such as fenofibrate, HMGCoA reductase inhibitors etc.；(3) hepatocyte protection medicine, such as Polyene Phosphatidylcholine, general sieve of sulphur
It is peaceful etc.；(4) Angiotensin Ⅱ receptor antagonist, such as Telmisartan；(5) slimming medicine, such as glucagon-like-peptide-1
(GLP-1) analog.
Insulin resistance is the essential characteristic of NAFLD patient, and Thiazolidinediones are that a kind of potent insulin increases
Quick dose, it can increase sensitiveness of the adipose tissue to insulin, and Primary Study finds that Thiazolidinediones can improve
NAFLD patients with insulin resistance and suppression inflammation reagentia, mitigate hepatic fat content, improve liver function, its mechanism
May be relevant with improvement insulin resistance, regulation cell factor etc., such medicine has turned into the one for the treatment of NAFLD great potentials
Class medicine.
Method Buddhist nun's ester X acceptors (FXR) are a kind of important nuclear factors, and research shows, FXR activation can strengthen insulin letter
Number conduction sensitiveness, reduce gluconeogenesis, reduce intrahepatic fat accumulation, alleviate fatty liver caused by liver fibrosis, in FXR
In depleted mice model, the level increase of the cholesterol and triglycerides of blood plasma and liver is detected, in the He of FXR depleted mices 9
During 12 monthly age, there are obvious hepatic injury and hepatocellular apoptosis, then occur adenoma of liver and hepatocellular carcinoma at 15 monthly age；FXR's matches somebody with somebody
Body or activator can suppress HSCs expression ECM, and increase ECM by activating FXR and FXR target gene SHP
Removing so that reduce ECM deposition, finally play treatment fibrosis effect.
Aspartic acid ornithine (Ornithine aspartate) is L-Orn and L-ASPARTIC ACID reacts a kind of stable compound to be formed, tool
There is increase to promote the effects such as liver cell metabolism, the reparation for participating in liver cell, clinically for because of acute and chronic hepatopathy (such as various liver
Inflammation, hepatic sclerosis, fatty liver, posthepatitic syndrome) trigger blood ammonia rise and hepatic encephalopathy, such as occur together or secondary to liver solution
Malicious function is damaged the potentiality or stage of attack hepatic encephalopathy of (such as hepatic sclerosis), and be particularly suitable for use in treatment hepatic coma early stage or hepatic coma
The confusional state of phase.
The content of the invention
The applicant is experimental studies have found that Ornithine aspartate and some reactive compound drug combinations hepatic disease excessive to fat accumulation
With good therapeutic action.
The purposes in preventing and treating fatty liver medicament is being prepared the invention provides a kind of pharmaceutical composition, it is characterised in that the combination
Thing is included：
(a) Ornithine aspartate or its pharmaceutically acceptable salt, or ornithine aspartate composition, or arginic paddy ammonia
Hydrochlorate (L-arginine Pidolidone), wherein described ornithine aspartate composition is by ornithine or its salt and L-aminobutanedioic acid
Or its salt composition, wherein the mol ratio of ornithine or its salt and L-aminobutanedioic acid or its salt is 10-1：1-10, or 8-1：1-8,
Or 5-1：1-5, or 3-1：1-3, or 2-1：1-2, preferably 1：1.
(b) following at least one active component or its officinal salt and pharmaceutical acceptable carrier are selected from：(1) vitamin E；(2) method
The part or farnesoid X receptor activator of Buddhist nun's alcohol X acceptors；(3) Thiazolidinediones；
The part or farnesoid X receptor activator of wherein described farnesoid X receptor are selected from following compounds or its is pharmaceutically acceptable
Salt, solvate or polymorph：Urso, sodium ursodexoxycholate, the water magnesium salts of urso three, shellfish cholic acid difficult to understand,
Tauro ursodesoxy cholic acid, TUDCANa, GW4064, Fexaramine, Turofexorate Isopropyl (XL335),
Px-104 or Px20606, preferably urso, shellfish cholic acid difficult to understand, Tauro ursodesoxy cholic acid.
Wherein described Thiazolidinediones be selected from (S)-((3,4- dihydro -2- (PHENYL-METHYL) -2H-1- chromene -6- bases) methyl -
Thiazolidine -2,4- diketone (Englitazone), 5 { [4- (3- (5- methyl -2- phenyl -4- oxazolyls) -1- oxopropyls)-phenyl]-methyl } -
Thiazolidine -2,4- diketone (Darglitazone), 5- { [4- ((1- methyl-cyclohexyls base) methoxyl group)-phenyl] methyl }-thiazolidine -2,4- bis-
Ketone (Ciglitazone), 5- { [4- (2- (1- indyls) ethyoxyl) phenyl] methyl }-thiazolidine -2,4- diketone (DRF2189),
5- { 4- [2- (5- methyl -2- phenyl -4- oxazolyls)-ethyoxyl] benzyl }-thiazolidine -2,4- diketone, 5- (2- Naphthylsulfonyls)-thiazolidine
- 2,4- diketone (AY-31637), double { 4- [(2,4- dioxo -5- thiazolidinyls) methyl] phenyl } methane, 5- { 4- [2- (5- methyl
- 2- phenyl -4- oxazolyls) -2- hydroxyl-oxethyls] benzyl }-thiazolidine -2,4- diketone (AD-5075), 5- [4- (1- phenyl -1- rings third
Alkyl carbonyl amino)-benzyl]-thiazolidine -2,4- diketone (DN-108), 5- { [4- (2- (2,3- indoline -1- bases) ethyoxyl) phenyl]
Methyl }-thiazolidine -2,4- diketone, 5- [3- (the chloro- phenyl of 4-) -2-propynyl] -5- phenyl sulfonyls)-thiazolidine -2,4- diketone, 5- [3- (4-
Chlorphenyl)] -2-propynyl] -5- (4- fluorophenyls-sulfonyl) thiazolidine -2,4- diketone, 5- { [4- (2- (methyl -2- pyridine radicals-amino)-second
Epoxide) phenyl] methyl }-thiazolidine -2,4- diketone (Rosiglitazone), 5- { [4- (2- (5- ethyl -2- pyridine radicals) ethyoxyl) phenyl] first
Base }-thiazolidine -2,4- diketone (Pioglitazone), 5- { [4- ((3,4- dihydro -6- hydroxyls -2,5,7,8- tetramethyl -2H-1- benzos
Pyrans -2- bases) methoxyl group)-phenyl]-methyl }-thiazolidine -2,4- diketone (troglitazone), 5- [6- (the fluoro- benzyloxies of 2-) naphthalene -2- Ji Jia
Base]-thiazolidine -2,4- diketone (MCC555), 5- { [benzoxazole -5- bases of 2- (2- naphthyls) -] methyl }-thiazolidine -2,4- diketone and 5- (2,
4- dioxothiazolidins -5- bases-methyl) -2- methoxyl groups-N- (4- romethyl-benzies) benzamide (KRP297), preferably pyrrole lattice row
Ketone.
In addition, the constituent of the present invention can further comprise such as VitAVitE, vitamin B1, vitamin B2、
Vitamin B3, vitamin B6, vitamin B12, folic acid, vitamin C, vitamin D3At least one of vitamin；Such as
The mineral matters such as copper, Determination, zinc；And other appropriate safe food additives.
Further, the mass ratio of Ornithine aspartate and Ao Bei cholic acid is 50~1000 in pharmaceutical composition provided by the present invention：1,
Or 800：1, or 700：1, or 600：1, or 500：1, or 400：1, or 300：1, or
150：1, or 100：1, or 50：1, preferably 600-1000:1, most preferably 600：1；
Further, Ornithine aspartate and using Pioglitazone as the thiazolidinediones of representative in pharmaceutical composition provided by the present invention
The mass ratio of medicine is 60~300：1, or 200：1, or 160：1, or 120：1, or 80：1, or 60：
1, preferably 120-200:1, most preferably 200：1；
Further, in pharmaceutical composition provided by the present invention, the aspartic acid ornithine (Ornithine aspartate) or its pharmacy
Upper acceptable salt consumption is daily 1mg/kg-50mg/kg, or is no more than 45mg/kg daily, or is no more than daily
40mg/kg, or 35mg/kg is no more than daily, or 30mg/kg is no more than daily, or 25mg/kg is no more than daily,
Or 20mg/kg is no more than daily, or 15mg/kg is no more than daily, or 10mg/kg is no more than daily, or daily not
More than 5mg/kg, or 1mg/kg is no more than daily, be preferably 20-40mg/kg daily.
The ligand content of the farnesoid X receptor is preferably no more than 10mg/kg daily to be no more than 20mg/kg daily；Wherein
Ursodeoxycholic acid content is no more than 15mg/kg to be daily, or is no more than 110mg/kg daily, or is no more than 5mg/kg daily,
It is preferred that being 6-10mg/kg daily；Shellfish cholic acid content difficult to understand is no more than 0.4mg/kg to be daily, or is no more than 0.3mg/kg daily,
Or 0.2mg/kg is no more than daily, or 0.1mg/kg is no more than daily, preferably it is 0.2mg/kg daily；Tauroursodeoxycholic Acid
Acid content is no more than 10mg/kg to be daily, or is no more than 8mg/kg daily, or is no more than 6mg/kg daily, or daily
No more than 4mg/kg, or 2mg/kg is no more than daily, be preferably 3-5mg/kg daily；
The consumption of the Thiazolidinediones is daily 0.05-0.5mg/kg, wherein：The Rosiglitazone content for daily not
More than 0.15mg/kg, or 0.13mg/kg is no more than daily, or is no more than 0.1mg/kg daily, or be no more than daily
0.08mg/kg, or 0.06mg/kg is no more than daily, or 0.05mg/kg is no more than daily, preferably it is daily
0.06-0.08mg/kg；Pioglitazone content is no more than 0.5mg/kg to be daily, or is no more than 0.4mg/kg daily, or daily
No more than 0.3mg/kg, or 0.2mg/kg is no more than daily, or is no more than 0.1mg/kg daily, be preferably daily
0.2-0.25mg/kg；
The purposes in preventing and treating fatty liver medicament is being prepared the invention provides described pharmaceutical composition and pharmaceutically acceptable carrier,
The fatty liver includes fat hepatitis, non-alcoholic fatty liver disease, nonalcoholic fatty liver disease, non-alcoholic fatty liver
Inflammation occur together liver fibrosis, nonalcoholic fatty liver disease occur together hepatic sclerosis, nonalcoholic fatty liver disease occur together hepatic sclerosis and liver it is thin
Born of the same parents' cancer, liver fibrosis, hepatic sclerosis and secondary fatty liver disease.
The composition of the present invention can be prepared as any form, for example particle, powder, tablet, coated tablet, capsule, pill,
Syrup, drops, solution, supensoid agent and emulsion, or active component sustained release preparation.
The constituent of the present invention can further comprise one or more medical or physiologically acceptable carriers, and these carriers will be appropriate
Prepare to be administered.For example, medical or physiologically acceptable carrier can be water, ringer's solution, buffered saline, grape
Sugar, maltodextrin, glycerine, alcohol, honey, mannitol, sorbierite, dextrin, lactose, caramel, gelatin, calcium sulfate,
Magnesium stearate, talcum powder, kaolin, tween, agar, calcium carbonate, calcium bicarbonate, surfactant, cyclodextrin and its spread out
Biology, phospholipid, phosphoric acid salt, starch and its derivative, silicon derivative, cellulose family and its derivative, pyrrolidones
One or more in class, polyethylene glycols, crylic acid resin, phthalate, acrylic copolymer, benzenetricarboxylic acid esters.
The constituent of the present invention can also include medical or physiologically acceptable additive, such as diluent, dispersant, surface
Activating agent, solvent, disintegrant, sweetener, adhesive, coating agent, foaming agent, lubricant, glidant or aromatic.
The constituent of the present invention can by all means be administered according to conventional method, including oral, intravenous, intra-arterial,
In intraperitoneal, thoracic cavity, transdermal, nasal cavity, suction, rectum, eye and subcutaneous import.
Beneficial effects of the present invention：
It is used to prepare lipotropic use after combining with shellfish cholic acid difficult to understand or Thiazolidinediones the invention provides Ornithine aspartate
On the way, Ornithine aspartate dosage is more much lower than individually giving Ornithine aspartate after drug regimen, and is used after drug regimen than folk prescription
Drug effect fruit is more excellent.Ornithine aspartate individually is given in clinical practice, dosage is larger so that Ornithine aspartate can only clinically be prepared
Limited formulation, such as granule, the present invention reduce the dosage of Ornithine aspartate by drug regimen, to develop more polymorphic type
Ornithine aspartate preparation provide may；Shellfish cholic acid or Thiazolidinediones consumption difficult to understand are seldom in drug regimen of the present invention simultaneously.
After drug regimen, shellfish cholic acid or Thiazolidinediones dosage difficult to understand are also than clinically much lower, due to its dosage
Reduction, shellfish cholic acid difficult to understand or Thiazolidinediones side effect can be also reduced to a certain degree.
Embodiment
Embodiment 1：Influence to the liver lipids and triglycerides of high fat diet obesity-induced mice
78 6 weeks big C57BL/6 mouse are divided into two groups, 6 are only given the normal diet (Normal group) containing 10% fat,
72 are only given the high fat diet containing 60% fat, raise 10 weeks, High fat diet mouse is separated into 12 groups：
Model group, the CMC-Na solution of daily gavage 0.5%；
Positive controls, give Ornithine aspartate 1g/kg daily；
1 group of drug regimen, gives Ornithine aspartate 0.6g/kg and shellfish cholic acid 4mg/kg difficult to understand daily；
2 groups of drug regimen, gives Ornithine aspartate 0.6g/kg and shellfish cholic acid 1mg/kg difficult to understand daily；
3 groups of drug regimen, gives Ornithine aspartate 0.6g/kg and shellfish cholic acid 0.6mg/kg difficult to understand daily；
4 groups of drug regimen, gives Ornithine aspartate 0.6g/kg and Pioglitazone 5mg/kg daily；
5 groups of drug regimen, gives Ornithine aspartate 0.6g/kg and Pioglitazone 3mg/kg daily；
6 groups of drug regimen, gives Ornithine aspartate 0.6g/kg and Pioglitazone 2mg/kg daily；
Above each group animal gave saline solution or medicine after 2 weeks, put to death animal, takes out part hepatic tissue (lobus sinister), makes group
Homogenate in 2: 1 chloroform/methanol solution (10mL) is woven in, and is filled into 15ml glass centrifuge tubes.The 2 of 5mL are added again:
1 chloroform/methanol solution, then adds 2.5ml 0.9%NaCl.After being thoroughly mixed, at 10 DEG C, carried with 2,000g centrifugations
Take thing 5 minutes, discard after water layer, organic layer is dried under a nitrogen, and assess by weighing total lipid content, ELISA examinations
The amount of the triglycerides gathered in agent box analysis hepatic tissue, testing result is shown in Table 1.
Table 1：Influence of the tested material to obesity mice liver lipid content and triglycerides
The fatty showed increased of model group mouse liver is can be seen that in result, and the drug combination of different portfolio ratios gives model mice
Afterwards, mouse liver fat is significantly reduced, and the drug regimen of this explanation present invention is more excellent than folk prescription administering effect, and reduction combination
The dosage of medicine still can reach that the consumption of shellfish cholic acid difficult to understand in identical effect, and drug regimen of the present invention at least can reach shellfish courage difficult to understand
Acid：Ornithine aspartate is 1：1000, the consumption of Rosiglitazone at least can reach Rosiglitazone：Ornithine aspartate is 1：300, except this,
Drug regimen of the present invention is low compared to folk prescription dosage.
Embodiment 2：Influence to the liver function of high fat diet obesity-induced mice
Animal packet and processing be the same as Example 1, before each group animal is put to death, take blood collected after centrifugation serum sample, ALT are used respectively
Transaminase in detection kit and AST detection kits measurement each group mice serum.
| Group | ALT(U/L) | AST(U/L) |
| Normal control | 30.5±24.2 | 45.8±8.5 |
| Model group | 254.1±32.3 | 437.1±36.6 |
| Positive control | 166.8±26.2 | 353.5±31.2 |
| Drug regimen 1 | 137.3±18.9 | 335.2±24.9 |
| Drug regimen 2 | 143.2±23.8 | 325.3±15.1 |
| Drug regimen 3 | 134.6±16.3 | 341.2±13.6 |
| Drug regimen 4 | 138.7±20.3 | 328.4±18.2 |
| Drug regimen 5 | 128.5±14.7 | 334.3±12.1 |
| Drug regimen 6 | 140.4±12.8 | 340.5±24.3 |
Table 2：Influence of the tested material to obesity mice serum transaminase
By can be seen that model group mice serum ALT, AST content is significantly raised compared with Normal group in result, and give
Mice serum ALT, AST content of different pharmaceutical portfolio ratio is decreased obviously compared with model group, is as a result illustrated in the present invention
Ornithine aspartate and related activity are medication combined to produce preferable effect, and reduction composition of medicine in the treatment to Rats adiposis hepatica
Dosage still can reach identical effect, except this, drug regimen of the present invention compared to folk prescription dosage it is low.
Embodiment 3：Prepare Ornithine aspartate composition granule
The Ornithine aspartate and Ao Bei cholic acid of quality such as take, add mannitol, Aspartame, citric acid and the alkene pyrrolidines of recipe quantity
Ketone-K30 the aqueous solution, stirs, the granulation of 16 mesh, dries, 14 mesh whole grains are produced.
Claims (10)
1. a kind of pharmaceutical composition is preparing the purposes in preventing and treating fatty liver medicament, it is characterised in that described pharmaceutical composition is included：
（a）Ornithine aspartate or its pharmaceutically acceptable salt；
（b）Selected from following at least one active component or its officinal salt and pharmaceutical acceptable carrier：（1）Shellfish cholic acid difficult to understand；（2）Thiazolidinediones.
2. purposes according to claim 1, it is characterised in that：The Thiazolidinediones are selected from Rosiglitazone, Pioglitazone, Ciglitazone, Darglitazone or Englitazone.
3. purposes according to claim 1, it is characterised in that：The Thiazolidinediones are selected from Pioglitazone.
4. purposes according to claim 1, it is characterised in that：The mass ratio of Ornithine aspartate and Ao Bei cholic acid is 50 ~ 1000 in pharmaceutical composition：1.
5. purposes according to claim 1, it is characterised in that：The mass ratio of Ornithine aspartate and Thiazolidinediones is 60 ~ 300 in pharmaceutical composition：1.
6. according to the purposes of claim 1 or 2, it is characterised in that：The Ornithine aspartate or its pharmaceutically acceptable salt content is daily no more than 40mg/kg.
7. according to the purposes of claim 1 or 2, it is characterised in that：The Ornithine aspartate or its pharmaceutically acceptable salt content is daily no more than 20mg/kg.
8. purposes according to claim 1, it is characterised in that：The shellfish cholic acid content difficult to understand is preferably no more than 0.1mg/kg daily to be no more than 0.2mg/kg daily.
9. purposes according to claim 2, it is characterised in that：The Rosiglitazone content is preferably no more than 0.07mg/kg daily to be no more than 0.15mg/kg daily；Pioglitazone content is preferably no more than 0.25mg/ kg daily to be no more than 0.5mg/kg daily.
10. according to any one of claim 1-9 purposes, it is characterised in that：The fatty liver includes fat hepatitis, non-alcoholic fatty liver disease, nonalcoholic fatty liver disease, nonalcoholic fatty liver disease occur together hepatic sclerosis, the nonalcoholic fatty liver disease of liver fibrosis, nonalcoholic fatty liver disease that occur together and occurred together hepatic sclerosis and hepatocellular carcinoma, liver fibrosis, hepatic sclerosis and secondary fatty liver disease.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107441089A (en) * | 2017-08-14 | 2017-12-08 | 合肥工业大学 | A kind of new application of row ketone medicine |
| CN109806386A (en) * | 2017-11-20 | 2019-05-28 | 江苏恒瑞医药股份有限公司 | The pharmaceutical composition and purposes of FXR agonist and GLP-1 analog |
| CN110507669A (en) * | 2019-09-24 | 2019-11-29 | 江西天元药业有限公司 | Refined bear gall powder and its treatment cholecystitis gallstones disease improve the purposes of gallbladder function |
| CN110507670A (en) * | 2019-09-24 | 2019-11-29 | 江西天元药业有限公司 | Refined bear gall powder and prophylactic treatment hepatopathy liver fibrosis improve the purposes of liver function |
| CN110548037A (en) * | 2019-09-24 | 2019-12-10 | 江西天元药业有限公司 | Refined bear gall powder and its use for strengthening physique, treating and preventing tumor and cancer |
| CN114340632A (en) * | 2019-08-30 | 2022-04-12 | 赛特瑞恩股份有限公司 | Pharmaceutical composition for treating or preventing nonalcoholic steatohepatitis (NASH) |
-
2015
- 2015-07-24 CN CN201510442089.1A patent/CN107028954A/en active Pending
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107441089A (en) * | 2017-08-14 | 2017-12-08 | 合肥工业大学 | A kind of new application of row ketone medicine |
| CN109806386A (en) * | 2017-11-20 | 2019-05-28 | 江苏恒瑞医药股份有限公司 | The pharmaceutical composition and purposes of FXR agonist and GLP-1 analog |
| CN114340632A (en) * | 2019-08-30 | 2022-04-12 | 赛特瑞恩股份有限公司 | Pharmaceutical composition for treating or preventing nonalcoholic steatohepatitis (NASH) |
| CN110507669A (en) * | 2019-09-24 | 2019-11-29 | 江西天元药业有限公司 | Refined bear gall powder and its treatment cholecystitis gallstones disease improve the purposes of gallbladder function |
| CN110507670A (en) * | 2019-09-24 | 2019-11-29 | 江西天元药业有限公司 | Refined bear gall powder and prophylactic treatment hepatopathy liver fibrosis improve the purposes of liver function |
| CN110548037A (en) * | 2019-09-24 | 2019-12-10 | 江西天元药业有限公司 | Refined bear gall powder and its use for strengthening physique, treating and preventing tumor and cancer |
| CN110507670B (en) * | 2019-09-24 | 2023-04-07 | 江西天元药业有限公司 | Refined bear gall powder and application of refined bear gall powder in preventing and treating liver diseases, liver fibrosis and improving liver function |
| CN110507669B (en) * | 2019-09-24 | 2023-05-02 | 江西天元药业有限公司 | Refined bear gall powder and its use for treating cholecystitis gall-stone and improving gall-bladder function |
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Application publication date: 20170811 |