CN104523662B - A kind of pharmaceutical composition for treating nonalcoholic fatty liver and its application - Google Patents
A kind of pharmaceutical composition for treating nonalcoholic fatty liver and its application Download PDFInfo
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- CN104523662B CN104523662B CN201410779018.6A CN201410779018A CN104523662B CN 104523662 B CN104523662 B CN 104523662B CN 201410779018 A CN201410779018 A CN 201410779018A CN 104523662 B CN104523662 B CN 104523662B
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- fatty liver
- nonalcoholic fatty
- fluorenes
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- aldehyde
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- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 title claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 title description 7
- 239000003814 drug Substances 0.000 claims description 16
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- 229940079593 drug Drugs 0.000 claims description 11
- -1 acetenyl Chemical group 0.000 claims description 10
- 231100000240 steatosis hepatitis Toxicity 0.000 claims description 9
- 208000004930 Fatty Liver Diseases 0.000 claims description 8
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 8
- 208000010706 fatty liver disease Diseases 0.000 claims description 8
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- 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
- 230000001476 alcoholic effect Effects 0.000 description 1
- 208000026594 alcoholic fatty liver disease Diseases 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of pharmaceutical composition for treating nonalcoholic fatty liver and its applications, the composition is prepared by active constituent and pharmaceutically acceptable auxiliary material, the active constituent includes 7 hydroxyl 1 ((4 hydroxy benzenes) acetenyl) 9,9 two (4 methoxybenzene) 9H fluorenes, 2 aldehyde.The effect of present invention prevention nonalcoholic fatty liver, is notable, 7 hydroxyl, 1 ((4 hydroxy benzenes) acetenyl) 9 being related to simultaneously, 9 two (4 methoxybenzene) 9H fluorenes, 2 aldehyde is natural products present in medicinal plant Selaginella pulvinata again, therefore natural environmental-protective, toxic side effect are low.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular to a kind of pharmaceutical composition for treating nonalcoholic fatty liver
Object and its application.
Background technology
In addition to alcohol, overnutrition, obesity, diabetes, hyperlipidemia, malnutrition etc. also easily cause the origin cause of formation of fatty liver
Fatty liver.When carbohydrate, the lipid content in food are excessively high, make liver fat synthesis excessive, be more than the limit of liver processing,
Increase burden of liver, disturb the metabolism to fat, broken the input and output balance of liver, fat is caused to be pushed in liver
And nonalcoholic fatty liver is formed, it is mainly liver cell Macrovesicular steatosis that basic pathology physiologic character, which changes,.Non- wine
Essence fatty liver is one of common chronic liver disease in China, and the illness rate of China and the Asian-Pacific area becomes in rising year by year in recent years
Gesture seriously endangers people's health.As diabetes and incidence of obesity increase, the incidence of nonalcoholic fatty liver is also year by year
Increase, if being prevented not in time, hepatic sclerosis or liver fibrosis can be developed into, directly influence the quality of life of patient, institute
To answer early stage diagnosis and treatment to nonalcoholic fatty liver, this is conducive to improve patient's outcome.
At present, clinically mainly include for the therapeutic scheme of the disease：Primary Care, such as lose weight, rationally keep on a diet and
It is appropriate to strengthen amount of exercise etc.；Liver injury medicament is avoided to take in；Hepatic treatment etc..Clinically common nonalcoholic fatty liver
Sick medicine has the drugs such as Radix Glycyrrhizae class, silymarin-group, bicyclic alcohols, Polyene Phosphatidylcholine and reduced glutathione.
These drugs have the effects that different degrees of anti-oxidant, anti-inflammatory and protection liver plasma membrane and organelle, and clinical practice can improve
Liver biochemical index.These drugs have expensive, and some effects are not notable.Therefore, research and development are safely and effectively treated non-
The medicine of alcoholic fatty liver disease has become the hot fields of current liver disease drug Therapy study.
CN103588616A discloses a kind of Selaginella pulvinata extract and its preparation method and application, is carried for Selaginella pulvinata
Object is taken to conduct in-depth research, with a variety of column chromatography separation technologies and half preparative high-performance liquid chromatographic separation method, extraction
A kind of compound (DZJB1-6) with the new skeleton structure of 9,9- diphenyl -1- (phenylacetylene base) -9H- fluorenes is separated to, and is disclosed
These compounds can significantly inhibit the activity of 4 type phosphodiesterases (PDE4), available for preparation PDE4 inhibitor, treat asthma,
Chronic obstructive pneumonia, inflammation etc..At present, still without this kind of compound of document report in terms of nonalcoholic fatty liver is prevented
Bioactivity.
Invention content
It is an object of the invention to be studied by the bioactivity to native compound monomer, a kind of plant source is provided
The drug of the treatment nonalcoholic fatty liver of property.The drug is with 7- hydroxyls -1- ((4- hydroxy benzenes) acetenyl) (the 4- first of -9,9- bis-
Oxygroup benzene) -9H- fluorenes -2- aldehyde be active constituent, available for overnutrition, obesity, diabetes, hyperlipidemia, malnutrition etc. because
Element causes the prevention and treatment of fatty liver.
In order to achieve the object of the present invention, inventor is fed using mouse as research object by high glucose and high fat high protein feed
It forms work(and establishes mouse non-alcoholic fatty liver disease model.By drug treatment, 7- hydroxyls -1- ((4- hydroxy benzenes) second is investigated
Alkynyl) therapeutic effect of (4- the methoxybenzenes) -9H- fluorenes -2- aldehyde of -9,9- bis- (DZJB-6) to non-alcoholic fatty liver disease, research
It was found that DZJB-6 has drug therapy effect to mouse non-alcoholic fatty liver disease.Therapeutic scheme is that high glucose and high fat high protein is fed
Mouse generates non-alcoholic fatty liver disease model, and mouse DZJB-6 is given by gavage, and administration group is respectively provided with 150mg/kg,
Two dosage groups of 50mg/kg, normal control and model control group give same volume excipient simultaneously.It is put to death after being administered 4 weeks
Animal mouse takes mice serum and liver to be analyzed.The experimental results showed that compared with Normal group, model control group
Serum TC, TG, GGT, ALT are significantly increased, and serum T P content is decreased obviously, and are respectively provided with statistical significance (P ＜ 0.05 or P ＜
0.01)；And serum TC, TG, GGT, ALT significantly reduce (P ＜ 0.05 or P ＜ after the medication of DZJB-6 high and low doses treatment group
0.01).It can be seen that DZJB-6 can effectively improve disorders of lipid metabolism caused by induction high in fat, accelerate fat transfer, prevent height
The non-alcoholic liver fat accumulation and fatty liver of fat induction have apparent anti-non-alcoholic fatty liver disease and liver function protecting
Effect.
Based on above-mentioned result of the test, technical solution provided by the invention is summarized as follows：
A kind of pharmaceutical composition for preventing nonalcoholic fatty liver, is prepared by active constituent and pharmaceutically acceptable auxiliary material
Form, the active constituent include 7- hydroxyls -1- ((4- hydroxy benzenes) acetenyl) -9,9- bis- (4- methoxybenzenes) -9H- fluorenes -
2- aldehyde.Preferably, the pharmaceutical composition of nonalcoholic fatty liver is prevented as described above, wherein the active constituent is by 7- hydroxyls
Base -1- ((4- hydroxy benzenes) acetenyl) (4- the methoxybenzenes) -9H- fluorenes -2- aldehyde of -9,9- bis- is formed as sole component.The chemical combination
The structural formula of object is shown below：
The pharmaceutical composition of prevention nonalcoholic fatty liver of the present invention, wherein 7- hydroxyls -1- ((4- hydroxy benzenes) acetylene
Base) (4- the methoxybenzenes) -9H- fluorenes -2- aldehyde of -9,9- bis- carried out relevant animal test as active constituent in a manner of gavage, it ties
Fruit drug is notable through gastrointestinal absorption, therefore the pharmaceutical composition can be oral preparation.The wherein described oral preparation packet
Include tablet, capsule, granule, dripping pill, oral liquid.It should be noted that according to the common process of formulation art, this field
Technical staff is easy to 7- hydroxyls -1- ((4- hydroxy benzenes) acetenyl) (4- the methoxybenzenes) -9H- fluorenes -2- aldehyde of -9,9- bis- and medicine
The upper acceptable auxiliary material of agent is prepared into common oral preparation, such as oral liquid, granule, tablet, capsule.Wherein, medicament
Acceptable auxiliary material includes filler, disintegrant, adhesive, corrigent, lubricant etc. on.The filler be selected from
Under it is one or more：Pregelatinized starch, lactose, mannitol and microcrystalline cellulose；The disintegrant is selected from following one kind
It is or a variety of：Sodium carboxymethyl starch, crospovidone, croscarmellose sodium and low-substituted hydroxypropyl cellulose；Described
Adhesive is selected from following one or more：Starch slurry, hydroxypropyl cellulose solution, povidone solution；The lubricant choosing
From following one or two：Magnesium stearate, talcum powder.
In addition, the present invention also provides a kind of compound new application, i.e.,：7- hydroxyls -1- ((4- hydroxy benzenes) acetenyl) -9,9-
Application of two (4- the methoxybenzenes) -9H- fluorenes -2- aldehyde in the drug for preparing prevention nonalcoholic fatty liver.Further, it is described
Nonalcoholic fatty liver be overnutrition, obesity, diabetes, hyperlipidemia and malnutritive any one or more of factor
Caused by fatty liver.
Compared with prior art, 7- hydroxyls -1- ((4- hydroxy benzenes) acetenyl) (the 4- methoxies of -9,9- bis- of the present invention
Base benzene) -9H- fluorenes -2- aldehyde prevention nonalcoholic fatty liver the effect of it is notable, while the compound is medicinal plant Selaginella pulvinata again
Present in natural products, therefore natural environmental-protective, toxic side effect are low.
Specific embodiment
Influence experiments of the embodiment 1DZJB-6 to mouse nonalcoholic fatty liver model
Kunming mouse 48, male, regular grade, weight 20-30g.All mouse are randomly divided into Normal group, model
Control group, DZJB-6 high and low doses treatment group, every group 12.In addition to Normal group is given normal diet and is fed, excess-three group
Give high glucose and high fat high protein feed (5% lard, 5% peanut oil, 2.8% cholesterol, 0.28% propylthiouracil (PTU), 20% sugarcane
Sugar, surplus are normal diet powder) feed progress modeling.After modeling from the 3rd week, DZJB-6 high and low doses group difference is daily
7- hydroxyls -1- ((4- hydroxy benzenes) acetenyl) -9,9- bis- (4- methoxybenzenes) -9H- fluorenes -2- aldehyde 150,50mg/kg gavages are given,
Normal group and model control group give normal saline gavage, and administration is for 4 weeks.During administration, except Normal group is given
Normal diet is given to feed outer, excess-three group is still fed to high glucose and high fat high protein feed.After last dose, eyeball of mouse
Take blood, EP pipes are collected, and are stored at room temperature rear 4000r/min centrifugations 5min, take serum do T-CHOL (TC), triglycerides (TG),
Glutamyl transferase (GGT), alanine aminotransferase (ALT), total protein (TP) detection.
The ordinary circumstance of each group animal is observed after administration, as a result, it has been found that：Normal group mouse active state is good,
There is seborrhea, liparotrichia, apocleisis etc., the activity of DZJB-6 high and low doses treatment group, diet shape in model control group mouse
State is preferable.In addition, each group mice serum TC, TG, GGT, ALT, TP changes of contents situation is shown in Table 1, table 2.Pass through the examination of table 1, table 2
It tests result to can be seen that compared with Normal group, serum TC, TG, GGT, ALT of model control group are significantly increased, serum T P
Content is decreased obviously, and is respectively provided with statistical significance (P ＜ 0.05 or P ＜ 0.01)；And after the medication of DZJB-6 high and low doses treatment group
Serum TC, TG, GGT, ALT significantly reduce (P ＜ 0.05 or P ＜ 0.01), this imply that 7- hydroxyls -1- ((4- hydroxy benzenes) acetylene
Base) -9,9- bis- (4- methoxybenzenes) -9H- fluorenes -2- aldehyde has nonalcoholic fatty liver preferable preventive and therapeutic effect.
1 each group mice serum TC, TG, GGT comparision contents of table
Model control group compared with Normal group,*P ＜ 0.05,**P ＜ 0.01；
Treatment group compared with model control group,#P ＜ 0.05,##P ＜ 0.01.
2 each group mice serum ALT, TP comparision contents of table
Model control group compared with Normal group,*P ＜ 0.05,**P ＜ 0.01；
Treatment group compared with model control group,#P ＜ 0.05,##P ＜ 0.01.
Claims (1)
1.7- hydroxyls -1- ((4- hydroxy benzenes) acetenyl) (4- the methoxybenzenes) -9H- fluorenes -2- aldehyde of -9,9- two is preparing the non-wine of prevention
Application in the drug of essence fatty liver, the nonalcoholic fatty liver for overnutrition, obesity, hyperlipidemia and nutrition not
Fatty liver caused by good any one or more of factor.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410779018.6A CN104523662B (en) | 2014-12-17 | 2014-12-17 | A kind of pharmaceutical composition for treating nonalcoholic fatty liver and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410779018.6A CN104523662B (en) | 2014-12-17 | 2014-12-17 | A kind of pharmaceutical composition for treating nonalcoholic fatty liver and its application |
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| CN104523662B true CN104523662B (en) | 2018-07-06 |
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