CN109893656A - MiR-327 inhibitor and/or FGF10 promotor are preventing and/or are treating the application in fat metabolism disease drug - Google Patents

MiR-327 inhibitor and/or FGF10 promotor are preventing and/or are treating the application in fat metabolism disease drug Download PDF

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CN109893656A
CN109893656A CN201711310808.XA CN201711310808A CN109893656A CN 109893656 A CN109893656 A CN 109893656A CN 201711310808 A CN201711310808 A CN 201711310808A CN 109893656 A CN109893656 A CN 109893656A
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drug
fgf10
inhibitor
prevention
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CN109893656B (en
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杨云龙
曹义海
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Yihui Science And Technology (shenzhen) Co Ltd
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Yihui Science And Technology (shenzhen) Co Ltd
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Abstract

The present invention provides miR-327 inhibitor and/or the new applications of FGF10 promotor, specifically the purposes in the drug of preparation prevention and/or treatment diabetes.MiR-327 inhibitor, FGF10 promotor can promote the increase of FGF10 in the stroma cell ingredient of adipose tissue, promote stroma cell constituents fats cell precursors to brown fat cell differentiation, improve energy consumption, promote the metabolism of fat, and then can achieve prevention and/or treat the effect of fat metabolism disease.The present invention also provides a kind of prevention and/or the drugs for the treatment of fat metabolism disease, including miR-327 inhibitor and its pharmaceutically acceptable carrier.

Description

MiR-327 inhibitor and/or FGF10 promotor are preventing and/or are treating fat metabolism Application in disease drug
Technical field
The present invention relates to technical field of pharmaceuticals, are preventing more particularly to miR-327 inhibitor and/or FGF10 promotor And/or the application in treatment fat metabolism disease drug.
Background technique
Fat metabolism is biological body fat with the help of various relevant enzymes, is digested and assimilated, the mistake of synthesis and decomposition Journey is processed into substance required for body, guarantees the running of normal physiological function, is of great significance for vital movement.Rouge The disease that fat metabolism causes extremely is modern society's common disease.Wherein, obesity is a kind of common fat metabolism disease, with body The volume of fat cell hypertrophy and cell number increase cause the percentage of body fat percentage of liveweight to increase extremely and excessively sink in certain parts With the characteristics of adipopexia fat.According to statistics, 15% -20% is accompanied by obesity in patient dead due to disease.Obesity is painstaking effort The breaking-out reason of pipe disease, especially coronary heart disease.Obesity also easily leads to the diseases such as fatty liver, cholecystitis, and therefore, treatment is fat Disease is particularly important to the health of people.
Currently, the method for the treatment of obesity has very much, including diet control, drug therapy, surgical intervention etc..Wherein, medicine Object therapeutic effect becomes apparent than the effect of diet control, and does not also need high spend of surgical intervention and tried hard to pursue greatly It holds in both hands.In the drug of commercially available treatment obesity, most drugs are all based on the methods of emetic, appetite-suppressing and take the photograph to reduce Enter intracorporal energy to achieve the purpose that weight-reducing, but this can generate certain harm and can not be fundamentally to health Change fat.Therefore, it is necessary to a kind of fundamentally prevention and/or fat metabolism disease is treated, while not damaging health again Drug.
Summary of the invention
To solve the above problems, the present invention provides a kind of miR-327 inhibitor in preparation prevention and/or to treat fatty generation Thank to the application in the drug of disease.MiR-327 inhibitor can significantly inhibit miR-327 in the stromal vascular fraction in adipose tissue Expression, miR-327 expression reduction, promote in non-fat cell (such as various types of cells in stromal vascular fraction) conduct MiR-327 target-increase of Fibroblast growth factor-10 (FGF10), promote in stromal vascular fraction before fat cell Body improves energy consumption, promotes the metabolism of fat, subtract to brown fat cell differentiation (i.e. promotion adipocyte precursor milkproduct) Small fat cell volume, to effectively improve and treat fat metabolism disease, especially obesity.
In a first aspect, the present invention provides miR-327 inhibitor and/or FGF10 promotor in preparation prevention and/or treatment Application in the drug of fat metabolism disease.
Wherein, the miR-327 inhibitor is used to inhibit the expression of miR-327 in lipid substrate vascular components (SVF), promotees Into the increase of the FGF10 as miR-327 target, adipocyte precursor in SVF is promoted to improve to brown fat cell differentiation Energy consumption promotes the metabolism of fat.And then it can achieve prevention and/or treat the effect of fat metabolism disease.
Wherein, the FGF10 promotor can promote the increase of FGF10 in lipid substrate vascular components (SVF), promote SVF Middle adipocyte precursor improves energy consumption to brown fat cell differentiation, promotes the metabolism of fat.And then it can achieve prevention And/or the effect for the treatment of fat metabolism disease.
Optionally, in the drug of the prevention and/or treatment fat metabolism disease simultaneously containing miR-327 inhibitor and FGF10 promotor.The two exists simultaneously down, can play the metabolism that collaboration promotes fat.
Wherein, the fat metabolism disease include obesity, fatty liver, hyperlipidemia, hyperlipoprotememia, cardiovascular disease, Ketosis, albumen reduce one of disease or a variety of, but not limited to this.
In the present invention, miR-327 is a kind of Microrna (MicroRNA), and short non-coding RNA adjusts egg after transcription White matter expression.
Optionally, the miR-327 inhibitor includes chemicals, polypeptide drug, the protide medicine for inhibiting miR-327 One of object and gene class drug are a variety of.
Further, the chemicals for inhibiting miR-327 refer generally to small molecular organic compounds.The inhibition miR- 327 protein medicaments include native protein, recombinant protein, including but not limited to antibody." the gene for inhibiting miR-327 Class drug " includes but is not limited to nucleic acid fragment, such as DNA fragmentation, RNA segment.
In an embodiment of the present invention, the miR-327 inhibitor is the LNA inhibitor probe of antagonism miR-327.It is described MiR-327 inhibitor can target and inhibit miR-327, and the miR-327 inhibitor is complementary with the sequence of miR-327.Wherein, The nucleotide sequence of miR-327 includes ACUUGAGGGGCAUGAGGAU.
Optionally, the FGF10 promotor includes promoting the increased chemicals of FGF10, polypeptide drug, protein drug With one of genomic medicine or a variety of.
Further, the increased chemicals of the promotion FGF10 refer generally to small molecular organic compounds.The promotion The increased protein medicaments of FGF10 include native protein, recombinant protein, including but not limited to antibody.The promotion FGF10 increases " gene class drug " include but is not limited to nucleic acid fragment, such as DNA fragmentation, RNA segment.Specifically, the FGF10 promotor Including FGF10 albumen.
Optionally, the pharmaceutically acceptable carrier includes solvent, polymer, liposome, recombinant viral vector and true At least one of core recombinant expression carrier, but not limited to this.
Wherein, the solvent includes but is not limited to water, physiological saline and other non-aqueous solvents.The recombinant virus Carrier may include one of slow virus carrier, adenovirus vector and retroviral vector or a variety of, but not limited to this.
Wherein, the polymer includes polylysine, polyethyleneimine (branch shape and/or chain) and its modifier, polyamides Amine-amine type dendrimer (PAMAM) and its derivative, polypropyleneimine dendrimer (PPI) and its derivative, shell One in glycan, poly lactic-co-glycolic acid (PLGA), polylactic acid, gelatin, cyclodextrin, sodium alginate, albumin and hemoglobin Kind is a variety of, but not limited to this.Wherein, polyethyleneimine and its modifier, PAMAM and its derivative, PPI and its derivative, Chitosan etc. can be described as cationic polymer.
The liposome can be by cation lipoid, neutral auxiliary lipoid, cholesterol, phosphatide (such as beans lecithin, yolk ovum Phosphatide, cephalin etc.) self assembly forms, can also be worn by distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) It inserts in the phospholipid layer of phospholipid molecule formation and is formed.
In the present invention, the effect of " pharmaceutically acceptable carrier " is the heretofore described drug of transport, makes its performance Due effect.In general, transport be from an organ or certain a part reach another organ or another Part, carrier must be mutually compatible with drug ingedient, not influence the biological activity of drug, and opposite is nontoxic, such as should Carrier enters in vivo without causing toxic side effect or the drug carried with it that serious reaction occurs, and does not generate to patient negative Face is rung.
Active pharmaceutical ingredient-miR-327 inhibitor and/or FGF10 promotor to disperse or be adsorbed in above-mentioned carrier and Dispersion is formed, can also be coated/be encapsulated by above-mentioned liposome, polymer etc., formation chondritic (such as nanocapsule Or micron capsule).For example, when the miR-327 inhibitor is to inhibit the nucleic acid fragment of miR-327, the prevention and/or treatment When the drug of fat metabolism disease, the drug include but is not limited to wrap up, combination or be blended have nucleic acid fragment cationic polymer, Polypeptide, protein drug etc..
Wherein, the miR-327 inhibitor being encapsulated in chondritic can carry out slow-release controlled-release or Targeting delivery, allow The drug plays optimal efficiency, additionally it is possible to improve the stability of the drug.For example, albumin, gelatin, shell are poly- Sugar, polylactic acid, which can generally form, can disperse or the microballoon of packaging medicine active constituent.
Optionally, in the drug of the prevention and/or treatment fat metabolism disease, the content of the miR-327 inhibitor is 5-20mg/kg.Further it is chosen as 5-10mg/kg.
Optionally, in the drug of the prevention and/or treatment fat metabolism disease, the content of the FGF10 promotor is 1- 100mg/kg。
Further, the content ratio of the miR-327 inhibitor and FGF10 promotor is (0.2-20): 1.
In the present invention, in the drug of the prevention and/or treatment fat metabolism disease, miR-327 inhibitor work can choose For single active ingredient, it also can choose FGF10 promotor as single active ingredient, can also press down using containing miR-327 Preparation and FGF10 promotor are as its active constituent.This is also " miR-327 inhibitor and/or FGF10 promotor " in the present invention Representative meaning.
On this basis, further, also contain other pharmacy in the drug of the prevention and/or treatment fat metabolism disease Upper acceptable active constituent.The miR-327 inhibitor and/or FGF10 promotor can pharmaceutically connect with described other The active constituent collective effect received achievees the purpose that prevention and/or treatment diabetes.
Wherein, other described pharmaceutically acceptable active constituents include in orlistat, 5-(4-chlorophenyl)-2,5-dihydro-3H-imadazo[2,1-a and Rimonabant It is one or more, but not limited to this.
The orlistat (Orlistat) is gastrointestinal lipases inhibitor, by directly blocking human body to rouge in food The absorption of fat, the thermal energy and fat of intake are once be less than consumption, and body fat is reduced naturally, to achieve the purpose that loss of weight.Institute Stating 5-(4-chlorophenyl)-2,5-dihydro-3H-imadazo[2,1-a (Mazindol) is appetite inhibitor, acts on non-organic simple obesity.The Rimonabant It (rimonabant) is 5- (4- chlorphenyl) -1- (2,4 dichloro benzene base) -4- methyl-N- (1- piperidyl) -1H- pyrazoles -3- first Amide is 1 antagonist of Cannabined receptor, can effectively mitigate obese patient's weight.Specifically, Austria can be selected according to actual needs Li Sita, 5-(4-chlorophenyl)-2,5-dihydro-3H-imadazo[2,1-a, Rimonabant or other drugs with prevention and/or treatment obesity.
Further, it is described prevention and/or treatment fat metabolism disease drug in, the miR-327 inhibitor and/or The mass ratio of FGF10 promotor and other pharmaceutically acceptable active constituents is (1-10): 1.
Optionally, it is described prevention and/or treatment fat metabolism disease drug in further include in diluent and excipient one Kind is a variety of.
The main function of the diluent is to fill the weight or volume of tablet consequently facilitating tabletting.Optionally, described dilute Releasing agent includes one of starch, carbohydrate, cellulose family and inorganic salts or a variety of.The excipient refers to removing in drug Key agents activity is at additives in addition, including binder, filler, disintegrating agent, lubricant in such as tablet, in pill Wine, vinegar, decoction etc., the base portion in semi-solid preparation ointment, creme, preservative in liquid preparation antioxidant, rectifys Taste agent, aromatic, cosolvent, emulsifier, solubilizer, osmotic pressure regulator, colorant etc..
Optionally, the form of the drug of the prevention and/or treatment fat metabolism disease includes tablet, capsule, pulvis, particle Agent, pill, syrup, solution or suspension.The form of the drug of the prevention and/or treatment fat metabolism disease depends on Application in practice.
Optionally, the drug of the prevention and/or treatment fat metabolism disease is applied by way of oral or injection.
Preferably, the drug of the prevention and/or treatment fat metabolism disease is applied by way of injection.Into at this point, institute State prevention and/or treat fat metabolism disease medicament forms be preferably solution, such as be dissolved in water or physiological saline in.Into One step, intraperitoneal injection, subcutaneous injection, intramuscular injection or the mode of intravenous injection of being injected through is applied.
Optionally, the drug of the prevention and/or treatment fat metabolism disease can pass through local administration or Formulations for systemic administration.
Optionally, the dosage of the drug of the prevention and/or treatment fat metabolism disease is daily 5-20 mgs/kg of body Weight.Specifically, the dosage of the drug of the prevention and/or treatment fat metabolism disease depends on many factors, including but not limited to Required biological activity and subject is to drug tolerance.
A kind of new application of miR-327 inhibitor and/or FGF10 promotor that first aspect present invention provides, specifically Purposes in the drug of preparation prevention and/or treatment fat metabolism disease, miR-327 inhibitor, FGF10 promotor can promote The increase of FGF10 in lipid substrate vascular components promotes adipocyte precursor in stromal vascular fraction to divide to brown fat cell Change, improve energy consumption, promote the metabolism of fat, and then can achieve prevention and/or treat the effect of fat metabolism disease.This hair The miR-327 inhibitor of bright offer and/or the new application of FGF10 promotor.For fat metabolism disease, especially fat and fat phase The treatment of related disorders opens new approach, has more significant prevention or therapeutic effect, can effectively reduce people and suffers from fatty generation Thank to disease, especially fat and obesity-related disease risk.
Second aspect, the present invention provides it is a kind of prevention and/or treatment fat metabolism disease drug, it is described prevention and/or The drug for treating fat metabolism disease includes one of miR-327 inhibitor and FGF10 promotor or a variety of, and pharmaceutically may be used The carrier of receiving.
The effect of the miR-327 inhibitor, the effect of FGF10 promotor, the pharmaceutically acceptable carrier are such as Described in first aspect present invention, which is not described herein again.
Wherein, the fat metabolism disease include obesity, fatty liver, hyperlipidemia, hyperlipoprotememia, cardiovascular disease, Ketosis, albumen reduce one of disease or a variety of, but not limited to this.
Optionally, in the drug of the prevention and/or treatment fat metabolism disease, the content of the miR-327 inhibitor is 5-20mg/kg。
Optionally, the drug of the prevention and/or treatment fat metabolism disease further includes other pharmaceutically acceptable activity Ingredient, other described pharmaceutically acceptable activity are at including one of orlistat, 5-(4-chlorophenyl)-2,5-dihydro-3H-imadazo[2,1-a and Rimonabant or a variety of.
Optionally, the mass ratio of the miR-327 inhibitor and other pharmaceutically acceptable active constituents is (1- 10): 1.
Optionally, the mass ratio of the FGF10 promotor and other pharmaceutically acceptable active constituents is (1- 10): 1.
A kind of prevention that second aspect of the present invention provides and/or the drug for treating fat metabolism disease, including miR-327 inhibit Agent and its pharmaceutically acceptable carrier.MiR-327 inhibitor in the drug can effectively inhibit lipid substrate vascular components The expression of middle miR-327 promotes the increase of FGF10, promotes adipocyte precursor to brown fat cell differentiation, improves energy and disappear Consumption promotes the metabolism of fat, and then improves fat metabolism disease.
The advantages of embodiment of the present invention, will partially illustrate in the following description, a part according to specification be it is aobvious and Be clear to, or can implementation through the embodiment of the present invention and know.
Detailed description of the invention
Fig. 1 is the histology result of the control group 2 and control group 3 whether giving medicine irritation;
Fig. 2 is the quantization figure of the fat cell average diameter of the control group 2 and control group 3 whether giving cold stimulation;
Fig. 3 is the adipose tissue mass test result of the control group 2 and control group 3 whether giving cold stimulation;
Fig. 4 is the histology result of the experimental group and control group 1 whether giving cold stimulation;
Fig. 5 is the metabolism test result of the experimental group and control group 1 whether giving cold stimulation.
Specific embodiment
As described below is the preferred embodiment of the embodiment of the present invention, it is noted that for the common skill of the art For art personnel, without departing from the principles of the embodiments of the present invention, several improvements and modifications can also be made, these improvement Also it is considered as the protection scope of the embodiment of the present invention with retouching.
Embodiment 1 is administered mouse, inquires into drug to the influence to adipose tissue mass and form
Experimental group: LNA inhibitor probe of the selection in the antagonism miR-327 that Exiqon company customizes presses down as miR-327 (the miR-327 inhibitor can target and inhibit mir-327 to preparation, and sequence is complementary with the nucleotide sequence of miR-327.Its The nucleotide sequence of middle miR-327 includes ACUUGAGGGGCAUGAGGAU).12 female C57BL/6 mouse of 8 week old are set Under neutral condition (30 DEG C), above-mentioned miR-327 inhibitor is subcutaneously injected weekly 1 to above-mentioned mouse with 8mg/kg dosage It is secondary, it then gives 6 mouse therein and carries out cold (4 DEG C) stimulations, in addition 6 are still placed at 30 DEG C and (do not give cold thorn Swash) (it should be noted that cold stimulation can also be replaced with to medicine irritation, such as β 3- adrenoceptor agonists thorn Swash).
Injection first carries out metabolic capability test to above-mentioned mouse after carrying out 2 weeks, 2 weeks altogether, specifically tests its maximal oxygen oxygen Ability (VO2), then reuse excessive CO2Mouse is put to death, careful its subcutaneous fat of dissection measures weight on precision balance, and It is for statistical analysis, obtain mouse adipose tissue weighing results.Histology is carried out to mouse adipose tissue simultaneously, it is specific to wrap It includes: adipose tissue being fixed using 4% PFA, is thinly sliced, digested using cathepsin K (20mM), and with 100% first Alcohol permeabilization.Sample is carried out to stay overnight closing using the 0.1%Triton X-100PBS solution containing 3% milk, at 4 DEG C and one It is anti-, such as AntiCD3 McAb 1 (1:100, catalog number (Cat.No.) AF3628, R&D) and anti-Perilipin (1:200, catalog number (Cat.No.) 20R-PP004, Fitzgerald Industries), anti-UCP1 (1:200, Abcam) etc. is incubated for.After being washed with PBS, sample is sealed with 3% milk It closes, and is incubated for 2 hours with the secondary antibody of fluorescent marker (1:300, Thermo Fisher Scientific Inc.) at room temperature. After flushing, sample load is observed and is measured on Laser Scanning Confocal Microscope (LSM510Confocal, Zeiss).
Control group 1: by do not inhibit miR-327 without effect miR mortifier drug (random sequence) with the dosage of 8mg/kg Weekly in subcutaneous injection to 12 C57BL/6 Mice Bodies of 8 week old, then gives 6 mouse therein and carry out cold (4 DEG C) Stimulation, in addition 6 are still placed at 30 DEG C and (do not give cold stimulation).It injects weekly 1 time, carries out 2 weeks altogether;It is first right after 2 weeks Mouse carries out VO2Test, then reuses excessive CO2Mouse is put to death, its adipose tissue is claimed by the above-mentioned method referred to Weight, and carry out histology.
Control group 2: the adenovirus vector (Vector Biosystems) of non-functional miR will be carried with 1 × 109PFU/ In each dosage subcutaneous injection to 24 C57BL/6 mouse white adiposes of 8 week old, 6 mouse are given after a week and are carried out Cold (4 DEG C) stimulations, in addition 6 are still placed at 30 DEG C;Give 6 mouse therein carry out medicine irritation (β 3- adrenaline by Body agonist (such as CL316243)), remaining 6 mouse saline injections are as a comparison.Excess CO is used after 2 weeks2It puts to death Mouse weighs to its adipose tissue by the above-mentioned method referred to and carries out histology.
Control group 3: the adenovirus (Ad-EF1a-mmu-mir-327-eGFP of miR-327 will be overexpressed;Vector Biosystems) with 1 × 109PFU/ each dosage is injected into 12 C57BL/6 mouse white adiposes of 8 week old, and one week After give 6 mouse therein and carry out cold (4 DEG C) stimulations, in addition 6 are still placed at 30 DEG C;Give 6 mouse therein into Row drug (such as CL316243) stimulation, remaining 6 mouse saline injections are as a comparison.Excess CO is used after 2 weeks2It puts to death Mouse weighs to its adipose tissue by the above-mentioned method referred to, and carries out histology.
Control group 2 and the histology result of control group 3 are as depicted in figs. 1 and 2, and Fig. 1 is control group 2 and control group 3 Histology result when whether giving medicine irritation.When Fig. 2 is whether control group 2 and control group 3 give cold stimulation The quantization of fat cell average diameter.Wherein, Ad-miRNC represents control group 2, and Ad-miR-327 represents control group 3.In Fig. 1, H&E, which is represented, carries out the dyeing of adipose tissue morphology using haematoxylin and Yihong.UCP1 dyeing display milkproduct position, PERI are shown Fat cell form, DAPI redye nucleus.
From in Fig. 1 and Fig. 2 as can be seen that for control group 3, the adenovirus of injection expression miR-327, simultaneously in mouse (Ad-miR-327 can be abbreviated as) after expression miR-327 in its adipose tissue, if promoting milkproduct without cold, drug etc. Stimulation, fat cell size are constant compared with control group 2.If when the stimulation for thering is cold, drug etc. to promote milkproduct, expression Its cell dia of the adipose tissue of miR-327 does not reduce and (is increased slightly), and UCP1 dyeing shows that its milkproduct degree reduces, arrow Head indicates the position of obvious milkproduct.
The result of Fig. 1 and Fig. 2 illustrates, imports miR-327 in mouse adipose tissue using viral vectors, can significantly inhibit White adipocyte milkproduct hinders combustion rouge effect.
Adipose tissue mass test result when Fig. 3 is whether control group 2 and control group 3 give cold stimulation.From Fig. 3 As can be seen that importing miR-327 in mouse adipose tissue using viral vectors, adipose tissue caused by cold stimulation can be inhibited Weight reduces, and hinders combustion rouge effect.
Experimental group and histology, the metabolism test result of control group 1 are as shown in Figure 4, Figure 5, wherein Inh-miR-NC Control group 1 is represented, Inh-miR-327 represents experimental group.
Figure 4, it is seen that after injecting miR-327 inhibitor to mouse, if promoting milkproduct without cold, drug etc. Stimulation, fat cell size is substantially reduced compared with control group 1, and UCP1 dyeing shows that its milkproduct degree significantly increases It is high.If have cold, drug etc. promote milkproduct stimulation, inject miR-327 inhibitor mouse fat cell size into One step reduces, and UCP1 dyeing shows that its milkproduct degree further increases, and arrow indicates the position of obvious milkproduct.
As seen from Figure 5, after injecting miR-327 inhibitor to mouse, if promoting the thorn of milkproduct without cold, drug etc. Swash, metabolic index significantly improves compared with control group 1.If when the stimulation for thering is cold, drug etc. to promote milkproduct, injecting miR- Its metabolic index of the mouse of 327 inhibitor further increases.
Therefore, Fig. 4-Fig. 5's the result shows that, can significantly promote the white adipose brown of mouse using miR-327 inhibitor Change, promote fat metabolism, reduces fat accumulation.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention Protect range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.

Claims (10)

1.miR-327 inhibitor and/or FGF10 promotor answering in the drug of preparation prevention and/or treatment fat metabolism disease With.
2. application as described in claim 1, which is characterized in that the miR-327 inhibitor and FGF10 promotor can promote The increase of FGF10 in the stromal vascular fraction of adipose tissue promotes in stromal vascular fraction adipocyte precursor to brown fat Cell differentiation improves energy consumption, promotes the metabolism of fat;Wherein, the miR-327 inhibitor is by inhibiting the matrix blood The increase of miR-327 expressed to promote the FGF10 as miR-327 target in pipe ingredient.
3. application as described in claim 1, which is characterized in that the fat metabolism disease includes obesity, fatty liver, high blood Rouge, hyperlipoprotememia, cardiovascular disease, ketosis, albumen reduce one of disease or a variety of.
4. application as described in claim 1, which is characterized in that the miR-327 inhibitor includes the chemistry for inhibiting miR-327 One of drug, polypeptide drug, protein drug and genomic medicine are a variety of;
The FGF10 promotor includes promoting the increased chemicals of FGF10, polypeptide drug, protein drug and genomic medicine One of or it is a variety of.
5. application as described in claim 1, which is characterized in that in the drug of the prevention and/or treatment fat metabolism disease also Including pharmaceutically acceptable carrier;The pharmaceutically acceptable carrier includes solvent, polymer, liposome, recombinant virus At least one of carrier and recombinant eukaryotic expression plasmid.
6. application as described in claim 1, which is characterized in that contain in the drug of the prevention and/or treatment fat metabolism disease There are miR-327 inhibitor and FGF10 promotor.
7. application as described in claim 1, which is characterized in that in the drug of the prevention and/or treatment fat metabolism disease also Containing other pharmaceutically acceptable active constituents, other described pharmaceutically acceptable active constituents include orlistat, horse One of indoles and Rimonabant are a variety of.
8. the drug of a kind of prevention and/or treatment fat metabolism disease, which is characterized in that promote including miR-327 inhibitor and FGF10 Into one of agent or a variety of and pharmaceutically acceptable carrier.
9. the drug of prevention as claimed in claim 8 and/or treatment fat metabolism disease, which is characterized in that the prevention and/or In the drug for treating fat metabolism disease, the content of the miR-327 inhibitor is 20-50mg/kg.
10. the drug of prevention as claimed in claim 8 and/or treatment fat metabolism disease, which is characterized in that the prevention and/ Or the form of the drug for the treatment of fat metabolism disease includes tablet, capsule, pulvis, granule, pill, syrup, solution or mixed Suspension;
The drug of the prevention and/or treatment fat metabolism disease is applied by way of oral or injection.
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