CN114288300A - Application of halofuginone in medicine for treating and preventing fatty liver and obesity - Google Patents
Application of halofuginone in medicine for treating and preventing fatty liver and obesity Download PDFInfo
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Abstract
The invention provides an application of halofuginone in preparing a medicament for treating and preventing fatty liver, obesity and related diseases. The invention also provides application of the compound based on halofuginone modification in preparing a medicament for treating and preventing fatty liver, obesity and related diseases and a pharmaceutical composition.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to application of halofuginone in preparing a medicine for treating and preventing fatty liver, obesity and related diseases.
Background
Non-alcoholic fatty liver disease (NAFLD), which is a metabolic disease of the liver that is pathologically changed by accumulation of triglyceride-based lipids in hepatocytes, has become one of the most common liver diseases worldwide, and the incidence rate thereof is still on the rise, and the number of cases of NAFLD is expected to expand from 8310 ten thousand cases (about 25% of the total population) in 2015 to 1.09 million cases in 2030 in the united states. Despite the steady progress currently made in elucidating the pathogenesis of NAFLD, targeting therapeutics, and advancing drug development, significant challenges remain unmet and no drugs are currently approved for the treatment of this disease.
Disclosure of Invention
In view of the above, in order to at least partially solve the above problems, the present invention provides the use of halofuginone and halofuginone modification-based compounds for the preparation of a medicament for the treatment and prevention of fatty liver, obesity and related diseases.
In order to achieve the above objects, one aspect of the present invention provides a use of halofuginone in the preparation of a medicament for the treatment and prevention of fatty liver, obesity and related diseases.
In another aspect of the present invention, there is provided a use of a compound based on halofuginone modification for the preparation of a medicament for the treatment and prevention of fatty liver, obesity and related diseases.
Wherein the halofuginone modification comprises at least one of: salifying modification, ester modification, amide modification, aminomethylation modification, etherification modification, ring-opening modification and cyclization modification.
According to an embodiment of the invention, the related diseases comprise at least one of: insulin resistance, metabolic syndrome, diabetes, hyperglycemia, hyperlipidemia, simple hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, liver cirrhosis, and liver cancer.
According to an embodiment of the invention, the drug comprises a pharmaceutical formulation formed by dissolution of a drug co-solvent.
In yet another aspect of the invention, a pharmaceutical composition is provided.
The pharmaceutical composition comprises halofuginone or a halofuginone-modified compound and related disease drugs, which are jointly used as active ingredients, and also comprises one or more pharmaceutically acceptable carriers and/or pharmaceutical excipients.
According to an embodiment of the invention, the carrier comprises a nanoemulsion or a microemulsion.
According to an embodiment of the invention, the pharmaceutical excipient comprises at least one of: polyethylene glycol, sodium carboxymethylcellulose and beta-cyclodextrin.
According to an embodiment of the invention, the related disease medication comprises at least one of: obeticholic acid, PPAR gamma ligand, ACC1/2 inhibitor.
According to an embodiment of the present invention, the PPAR γ ligand includes pioglitazone, thiazolidinediones.
According to embodiments of the invention, ACC1/2 inhibitors include PF-05221304, ND-630.
According to the embodiment of the invention, in the application of the halofuginone, the halofuginone can inhibit liver fat deposition, improve fatty liver symptoms and liver function indexes, enhance sugar tolerance, improve insulin resistance and generate positive effects on metabolic health.
Drawings
FIG. 1 is a schematic diagram showing the experimental procedure of the present invention for C57 mouse;
FIG. 2(a) is a graph showing a comparison of body types of C57 mice administered with the example of the present invention;
FIG. 2(b) shows the body weight change curve during the experiment of the example of the present invention on C57 mice;
fig. 2(C) shows a statistical graph of mean food intake on a 3-balance of C57 mice fed high fat diet according to an embodiment of the present invention;
FIG. 3(a) is a statistical graph showing the mass/body weight ratio of white fat (epididymal fat and inguinal fat) of C57 mice treated with the example drug of the present invention;
FIG. 3(b) shows a statistical plot of the mass/body weight ratio of brown fat in C57 mice treated with the example of the present invention;
FIG. 3(C) shows a statistical plot of the liver weight of C57 mice treated with the example drugs of the present invention;
figure 4(a) shows the effect of treatment with an example of the invention on glucose tolerance in C57 mice;
fig. 4(b) shows a statistical plot of the area under the blood glucose concentration curve in the glucose tolerance test of C57 mice for the administration treatment of the examples of the present invention;
FIG. 4(C) shows the effect of treatment with an embodiment of the invention on insulin tolerance in C57 mice;
FIG. 4(d) is a statistical plot of the area under the blood glucose concentration curve in the insulin tolerance test of C57 mice treated with the administration of the example of the present invention;
FIG. 5 shows the results of oil-red-O staining of livers and liver cryosections of C57 mice after treatment with administration of an example of the present invention;
FIG. 6(a) shows the effect of treatment with the present invention on serum glutamic-oxaloacetic transaminase levels in C57 mice;
FIG. 6(b) is a graph showing the effect of treatment with the example of the present invention on serum glutamate pyruvate transaminase levels in C57 mice;
FIG. 7(a) shows the effect of treatment with the example of the invention on serum triglyceride levels in C57 mice;
FIG. 7(b) shows the effect of treatment with the example of the present invention on serum cholesterol levels in C57 mice.
Detailed Description
In order that the objects, technical solutions and advantages of the present invention will become more apparent, the present invention will be further described in detail with reference to the accompanying drawings in conjunction with the following specific embodiments.
The efficacy of several drugs in clinical trials is remarkable among drugs of fatty liver, obesity and related diseases, such as FXR agonists (obeticholic acid), but these findings need to be translated into long-lasting safety and efficacy. PPAR γ ligands (e.g., pioglitazone, members of the thiazolidinedione family of drugs) have been studied in several trials to ameliorate steatosis, inflammation and hepatocellular ballooning and liver fibrosis; however, they are limited by side effects such as weight gain, fluid retention, reduced bone mass and increased risk of fracture. The ACC1/2 inhibitor PF-05221304, at increasing doses, increased the proportion of asymptomatic hypertriglyceridemia patients. The invention provides a new therapeutic drug for treating fatty liver, obesity and related diseases, can obviously improve fatty degeneration of liver, reduce the concentration of serum triglyceride and reduce the levels of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase which are related indexes of hepatotoxicity, and has good application value.
The invention provides an application of halofuginone in preparing a medicament for treating and preventing fatty liver, obesity and related diseases.
Wherein the chemical structural formula of the halofuginone is shown as the following formula (1):
the invention also provides application of the dichroa febrifuga ketone modified compound in preparing medicines for treating and preventing fatty liver, obesity and related diseases.
According to an embodiment of the invention, the related diseases comprise at least one of: insulin resistance, metabolic syndrome, diabetes, hyperglycemia, hyperlipidemia, simple hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, liver cirrhosis, and liver cancer.
The drug may include a pharmaceutical formulation formed by dissolution of a drug co-solvent. Wherein, the drug cosolvent can be a pharmaceutically acceptable solvent which does not damage the active ingredients of halofuginone, and is not particularly limited.
Halofuginone modification-based compounds can be used to modify functional groups in halofuginone using methods known in the art, and are included in the present invention as long as they remain pharmaceutically acceptable without destroying the active ingredient of halofuginone. Wherein halofuginone modifications may include, but are not limited to, at least one of: salifying modification, ester modification, amide modification, aminomethylation modification, etherification modification, ring-opening modification and cyclization modification.
Application of the halofuginone or the halofuginone modified compound in preparation of medicines for treating and preventing fatty liver, obesity and related diseases and also provides a pharmaceutical composition. The pharmaceutical composition comprises halofuginone or a halofuginone-modified compound and related disease drugs, which are jointly used as active ingredients, and also comprises one or more pharmaceutically acceptable carriers and/or pharmaceutical excipients. The pharmaceutical composition can be applied to the preparation of medicines for treating and preventing fatty liver, obesity and related diseases.
According to an embodiment of the invention, the carrier comprises a nanoemulsion or a microemulsion.
According to an embodiment of the invention, the pharmaceutical excipient comprises at least one of: polyethylene glycol, sodium carboxymethylcellulose and beta-cyclodextrin.
According to an embodiment of the invention, the related disease medication comprises at least one of: obeticholic acid, PPAR gamma ligand, ACC1/2 inhibitor. The PPAR gamma ligand can comprise pioglitazone and thiazolidinediones. ACC1/2 inhibitors may include PF-05221304, ND-630.
It should be noted that, in the present invention, the effective dosage of the used drug cosolvent, carrier or pharmaceutical adjuvant can be specifically determined according to the pharmaceutically acceptable dosage.
The dosage of halofuginone or halofuginone-modified-based compound or pharmaceutical composition to be administered may be determined according to the route of administration, pharmacokinetic parameters of halofuginone, grade of the associated disease, and health condition of the subject, etc.
The following description will schematically illustrate the role of halofuginone in fatty liver, obesity and related diseases with reference to fig. 1 to 7. It should be noted that the illustration is only a specific embodiment of the present invention, and does not limit the protection scope of the present invention.
Preparation of experimental mice: SPF grade C57 mice (8 weeks old, male) were purchased from Jiangsu Jiejiekang Biotech, Inc., and housed in the animal center, university of science and technology, China, with sterile padding replaced once a week to obtain free access to food and water.
FIG. 1 schematically shows a schematic experimental scheme of an embodiment of the present invention on C57 mice.
As shown in fig. 1, the administration and treatment of animals are specified as follows: c57 mice were randomly divided into a high fat diet (60% fat) group and a normal diet group (3: 1) after one week of acclimation in the animal room, and after 12 weeks of feeding, the high fat diet group was divided into 3 groups (vehicle control group, low dose group (halofuginone content 100 μ g/kg), high dose group (halofuginone content 250 μ g/kg)). Halofuginone hydrobromide was purchased from Shanghai ceramic Biotech Ltd. The medicine is prepared into 30mg/mL mother solution in dimethyl sulfoxide and stored in a refrigerator at the temperature of 20 ℃ below zero. The drug is prepared into 0.03mg/mL and 0.075mg/mL concentrations in 0.5% sodium carboxymethylcellulose before administration, and mice are injected intraperitoneally at a dose of 100 μ g/kg or 250 μ g/kg once every two days for a dosing period of 12 weeks.
During dosing, mice were weighed once a week. Mice were harvested at the end of 24 weeks for subsequent molecular and pathological experiments.
In the present embodiment, all data are processed and statistically analyzed by using Graphpad Prism 8.0 software, and the mean value of the samples is analyzed by using One-way ANOVA or two-way ANOVA. p <0.05 indicates a statistical difference. *: p <0.05, x: p <0.01, x: p <0.001, x: p < 0.0001.
Example 1: effect of halofuginone on mouse body weight and diet
FIG. 2(a) shows a comparison of the body types of C57 mice administered with the example of the present invention; FIG. 2(b) shows the body weight change curve during the experiment of the example of the present invention on C57 mice; fig. 2(C) shows a statistical graph of mean food intake on a 3-scale of C57 mice fed high fat diet according to an example of the present invention.
In this example, the body weight of the mice was measured once a week during the 24-week experiment as shown in fig. 2 (b). As shown in fig. 2(a), photographing at the end point recorded the body type differences of mice, wherein, in fig. 2(a), from left to right, the normal diet group (fed with normal diet, administered with vehicle), the high fat diet (fed with vehicle control group), the high fat diet (fed with low dose group, in which the halofuginone content is 100 μ g/kg), and the high fat diet (fed with high dose group, in which the halofuginone content is 250 μ g/kg), respectively. At the last week, the mice were placed in a metabolism cage (Promethion) for 4 days and the diet of the mice was recorded, and the data source was the average daily food weight excluding the first day, and the average daily food intake weight of the mice was recorded, as shown in fig. 2 (c).
As shown in the above-mentioned FIGS. 2(a) to 2(c), the weight of the mice was significantly reduced in both the low dose group (containing halofuginone in an amount of 100. mu.g/kg) and the high dose group (containing halofuginone in an amount of 250. mu.g/kg) and the food intake amount of the mice was increased as compared with the vehicle control group.
Example 2: effect of halofuginone on fat weight and liver weight in mice
FIG. 3(a) is a statistical graph showing the mass/body weight ratio of white fat (epididymal fat and inguinal fat) of C57 mice treated with the example drug of the present invention; FIG. 3(b) shows a statistical plot of the mass/body weight ratio of brown fat in C57 mice treated with the example of the present invention; fig. 3(C) shows a statistical plot of the liver weight of C57 mice treated with the administration of the present invention.
In this example, after 24 weeks of the respective treatments of each group of mice, white fat (epididymal fat and inguinal fat) and brown fat at the scapula were completely removed, weighed, and the fat mass/body weight ratio of the mice was calculated, and the statistical results are shown in fig. 3(a) and 3 (b).
The experimental results are as follows: compared with the solvent control group, the low-dose group (halofuginone content is 100 mug/kg) and the high-dose group (halofuginone content is 250 mug/kg) can both obviously reduce the white fat content, and have no influence on the brown fat content.
In this example, after the treatment of each group of mice for 24 weeks, the livers of the mice were simultaneously removed and weighed, as shown in fig. 3 (c).
The experimental results are as follows: liver weights were significantly reduced in the low dose group (halofuginone content 100. mu.g/kg) mice compared to the vehicle control group.
Example 3: effect of halofuginone on glucose tolerance and insulin resistance in mice
In this example, glucose tolerance and insulin tolerance experiments were performed at week 22 and week 23, respectively.
The sugar tolerance test procedure may be: the mice are placed in a clean and feed-free cage one night before the experiment, fasting is carried out for 16h, 0.5g/mL glucose solution is prepared before the experiment, the weight of the mice is weighed, 0min fasting blood glucose is measured before glucose injection, then glucose is injected, wherein the injection dose can be 2g/kg, and the blood glucose concentration after glucose injection (15min, 30min, 60min, 90min and 120min) is measured.
The insulin tolerance test procedure may be: the weight of the mice was measured before the experiment, 0.2U/mL insulin solution was prepared on the day of the experiment, and the mice were placed in clean cages and fasted for 4h on the day of the experiment. Fasting blood glucose is measured 0min before insulin injection, followed by insulin injection, at a dose of 0.5U/kg, and the blood glucose concentration is measured after glucose injection (15min, 30min, 45min, 60min, 90min, 120 min).
Figure 4(a) shows the effect of treatment with an example of the invention on glucose tolerance in C57 mice; fig. 4(b) shows a statistical plot of the area under the blood glucose concentration curve in the glucose tolerance test of C57 mice for the administration treatment of the examples of the present invention; FIG. 4(C) shows the effect of treatment with an embodiment of the invention on insulin tolerance in C57 mice; fig. 4(d) shows a statistical plot of the area under the blood glucose concentration curve in the insulin tolerance test of C57 mice treated with the administration of the example of the present invention.
The experimental results are as follows: as shown in FIGS. 4(a) to 4(d), both the low dose group (halofuginone content 100. mu.g/kg) and the high dose group (halofuginone content 250. mu.g/kg) were able to increase glucose tolerance and improve insulin resistance in mice as compared with the vehicle control group.
Example 4: effect of halofuginone on hepatic steatosis
FIG. 5 shows the results of oil-red O staining of livers and liver cryosections of C57 mice after treatment with the administration of the example of the invention.
In this example, each group of mice was treated for 24 weeks, and then the whole liver was removed, as shown in fig. 5, after the liver was photographed and weighed, the lobules of the same portion were cut out and fixed in paraformaldehyde overnight, washed with PBS the next day and dehydrated in 30% sucrose, the liver was embedded in a freezing embedding medium on the third day, and the embedded liver was sliced continuously in a freezing microtome. The slices are stored at-80 deg.C, and taken out when used, and re-warmed at room temperature for 20 min. Then dyeing is carried out.
Wherein, the dyeing step may include, but is not limited to, the following steps:
the first step is as follows: the sections were washed 2-3 times with PBS for 5min each time, allowed to stand up and blotted dry with filter paper, and then circled with a organizing pen.
The second step is that: 60% isopropyl alcohol wash 10s, pour off the supernatant, set up the sections and blot them dry with filter paper.
The third step: the tissue sections were immersed in 0.3% oil red O staining solution for 1 min.
The fourth step: the solution was washed with 60% isopropanol for 10s and the supernatant was decanted off.
The fifth step: wash once with PBS (care was taken to work slowly during washing), pour off the supernatant and blot dry with paper.
And a sixth step: glycerol gelatin (preheated at 60-70 ℃) was mounted, a drop was placed on the slide, and the slide was covered with a cover slip. After completion, the microscope takes a picture.
The experimental results are as follows: as shown in FIG. 5, the low dose group (halofuginone content 100. mu.g/kg) and the high dose group (halofuginone content 250. mu.g/kg) both reduced liver fat deposition in mice compared to the vehicle control group; among them, the low dose group (100. mu.g/kg) was more effective in alleviating fatty liver in comparison.
Example 5: influence of halofuginone on serum glutamic-oxaloacetic transaminase (AST) content and serum glutamic-pyruvic transaminase (ALT) content of mice
FIG. 6(a) shows the effect of treatment with the present invention on serum glutamic-oxaloacetic transaminase levels in C57 mice; FIG. 6(b) shows the effect of treatment with the example of the present invention on serum glutamate pyruvate transaminase levels in C57 mice.
In this example, the measurement of serum aspartate Aminotransferase (AST) and serum alanine Aminotransferase (ALT) in mice was entrusted to Wuhanseville Biotech Ltd.
The experimental results are as follows: as shown in FIGS. 6(a) and 6(b), the serum glutamic-oxaloacetic transaminase (KG) and glutamic-pyruvic transaminase (GPT) levels of C57 mice were lower in both the low dose group (halofuginone content: 100. mu.g/kg) and the high dose group (halofuginone content: 250. mu.g/kg) than in the vehicle control group. The result shows that the halofuginone can remarkably reduce the elevation of AST and ALT in the liver caused by high-fat feed feeding and reverse the liver function damage.
Example 6: effect of halofuginone on serum Triglyceride (TG) and serum Cholesterol (CHO) levels in mice
FIG. 7(a) shows the effect of treatment with the example of the invention on serum triglyceride levels in C57 mice; FIG. 7(b) shows the effect of treatment with the example of the present invention on serum cholesterol levels in C57 mice.
In this example, the measurement of serum Triglyceride (TG) content and serum Cholesterol (CHO) content in mice was entrusted to Wuhansevier Biotech Ltd.
The experimental results are as follows: as shown in FIGS. 7(a) and 7(b), the serum Triglyceride (TG) content and the serum Cholesterol (CHO) content of C57 mice were lower in both the low dose group (halofuginone content: 100. mu.g/kg) and the high dose group (halofuginone content: 250. mu.g/kg) than in the vehicle control group. The halofuginone is shown to be capable of remarkably reducing the content of serum TG and CHO.
Weight loss due to dietary and lifestyle interventions reduces the transport of metabolic substrates to the liver and can improve all features of non-alcoholic fatty liver, including liver fibrosis. The application of the halofuginone provided by the invention can effectively reduce the weight increase of mice caused by high-fat diet, inhibit liver fat deposition, improve fatty liver symptoms and liver function indexes, enhance sugar tolerance, improve insulin resistance and generate positive effects on metabolic health under the condition of not limiting diet.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention and are not intended to limit the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. An application of halofuginone in preparing the medicines for preventing and treating fatty liver, obesity and relative diseases is disclosed.
2. Use of a compound based on halofuginone modification for the manufacture of a medicament for the treatment and prevention of fatty liver, obesity and related diseases, wherein said halofuginone modification comprises at least one of: salifying modification, ester modification, amide modification, aminomethylation modification, etherification modification, ring-opening modification and cyclization modification.
3. The use of claim 1 or 2, wherein the associated disease comprises at least one of: insulin resistance, metabolic syndrome, diabetes, hyperglycemia, hyperlipidemia, simple hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, liver cirrhosis, and liver cancer.
4. The use of claim 1 or 2, wherein the medicament comprises a pharmaceutical formulation formed by dissolution with a drug co-solvent.
5. A pharmaceutical composition is characterized by comprising halofuginone or a halofuginone modification-based compound and related disease drugs which are jointly used as active ingredients, and also comprising one or more pharmaceutically acceptable carriers and/or pharmaceutical auxiliary materials.
6. The pharmaceutical composition of claim 5, wherein the carrier comprises a nanoemulsion or microemulsion.
7. The pharmaceutical composition of claim 5, wherein the pharmaceutical excipient comprises at least one of: polyethylene glycol, sodium carboxymethylcellulose and beta-cyclodextrin.
8. The pharmaceutical composition of claim 5, wherein the related disease drug comprises at least one of: obeticholic acid, PPAR gamma ligand, ACC1/2 inhibitor.
9. The pharmaceutical composition of claim 5, wherein the PPAR γ ligand comprises pioglitazone, thiazolidinediones.
10. The pharmaceutical composition of claim 5, wherein said ACC1/2 inhibitor comprises PF-05221304, ND-630.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110212165A1 (en) * | 2005-02-23 | 2011-09-01 | Mordechai Erez | Pharmaceutical compositions of the isolated d-enantiomer of the quinazolinone derivative halofuginone |
| US20150004133A1 (en) * | 2013-06-07 | 2015-01-01 | The Regents Of The University Of California | Compositions And Methods For Treating Steatohepatitis, Liver Fibrosis, and Hepatocellular Carcinoma (HCC) |
| US20150057297A1 (en) * | 2012-01-13 | 2015-02-26 | President And Fellows Of Harvard College | Halofuginol derivatives and their use in cosmetic and pharmaceutical compositions |
| CN106539754A (en) * | 2016-11-25 | 2017-03-29 | 河北科星药业有限公司 | Hydrobromic acid antifebrile dichroanone solution and preparation method thereof |
-
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110212165A1 (en) * | 2005-02-23 | 2011-09-01 | Mordechai Erez | Pharmaceutical compositions of the isolated d-enantiomer of the quinazolinone derivative halofuginone |
| US20150057297A1 (en) * | 2012-01-13 | 2015-02-26 | President And Fellows Of Harvard College | Halofuginol derivatives and their use in cosmetic and pharmaceutical compositions |
| US20150004133A1 (en) * | 2013-06-07 | 2015-01-01 | The Regents Of The University Of California | Compositions And Methods For Treating Steatohepatitis, Liver Fibrosis, and Hepatocellular Carcinoma (HCC) |
| CN106539754A (en) * | 2016-11-25 | 2017-03-29 | 河北科星药业有限公司 | Hydrobromic acid antifebrile dichroanone solution and preparation method thereof |
Non-Patent Citations (5)
| Title |
|---|
| CARL J. DESELM: "Halofuginone Prevents Estrogen-Deficient Osteoporosis in Mice", 《J CELL BIOCHEM. 》 * |
| GUOQING CHEN: "Halofuginone and artemisinin synergistically arrest cancer cells at the G1/G0 phase by upregulating p21Cip1 and p27Kip1", 《ONCOTARGET》 * |
| J. LIANG: "The Effect of Antifibrotic Drug Halofugine on Th17 Cells in Concanavalin A-Induced Liver Fibrosis", 《SCANDINAVIAN JOURNAL OF IMMUNOLOGY》 * |
| SIMONA ROLLA: "The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice", 《CLINICAL SCIENCE》 * |
| YULIA GNAINSKY: "Involvement of the tyrosine phosphatase early gene of liver regeneration (PRL–1) in cell cycle and in liver regeneration and fibrosis effect of halofuginone", 《CELL TISSUE RES》 * |
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