CN103316031A - Weight reduction and body fat reduction applications of chitosan oligosaccharide - Google Patents
Weight reduction and body fat reduction applications of chitosan oligosaccharide Download PDFInfo
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Abstract
The invention relates to the technical field of medicine, particularly to applications of chitosan oligosaccharide. According to the present invention, chitosan oligosaccharide is applied in preparation of drugs with functions of weight reduction and/or body fat reduction, and chitosan oligosaccharide with a number average molecular weight of not more than 3000 is preferably selected, wherein the chitosan oligosaccharide with different number average molecular weights provides significant application effects in body weight control, body fat ratio reduction, and reduction of total cholesterol and/or low density lipoprotein cholesterol in blood serum. In addition, the chitosan oligosaccharide has effects of weight reduction, body fat reduction, fatty liver alleviating and reduction of blood fat in blood serum.
Description
Technical field
The present invention relates to medical technical field, the Weight-reducing and lipid-lowering that is specifically related to a kind of oligochitosan is used.
Background technology
Obesity is a kind of chronic nutritional disease that the energy metabolism disequilibrium of body causes, and looks about the whole world, and each country of obese people number is raising.U.S. adults has 66% to be overweight or fat, and incidence of obesity is 32%.And in China, end 2009, and the male overweight ratio has reached 11.4%, and the women has reached 10.1%, male's abdominal obesity ratio 27.8%, women's abdominal obesity 45.9%.Studies show that obesity can be caused by many factors such as gene, diet, environment, tradition, is the predisposing factor of the various diseases such as non-alcohol fatty liver (NAFLD), type Ⅱdiabetes mellitus, atherosclerosis (AS), tumor, sleep disorder, osteoarthritis.So seek the study hotspot that appetrol safely and effectively become pharmaceutical sanitary field.
Oligochitosan (chitosan oligosaccharides/chitooligosacchrides, COS), be glucosamine and 2-Acetamido-2-deoxy-D-glucose with homopolymer or heteropolymer that β-the Isosorbide-5-Nitrae glycosidic bond is formed by connecting, it is present known unique alkaline oligosaccharide, oligochitosan is by degradation of chitin, good water solubility easily absorbs, and human body is had no side effect, good biocompatibility, its physiologically active is compared chitin with functional character and is significantly improved.Research finds that oligochitosan has certain effect to neuroprotective, antitumor, antibacterial, antiinflammatory, blood sugar lowering, antioxidation, liver protection etc., but application system is indefinite, causes effect unstable, has affected further applying of oligochitosan.
Summary of the invention
The technical problem to be solved in the present invention is to fill up the application deficiency of existing oligochitosan, and the application of oligochitosan aspect preparation fat-reducing and/or fat-reducing medicament is provided.
Purpose of the present invention is achieved by the following technical programs:
The application of oligochitosan is provided, specifically is applied to prepare the medicine aspect of fat-reducing and/or blood fat reducing.
Preferably, described application is that oligochitosan is applied to prepare the medicine aspect of controlling body weight.
Preferably, be applied to prepare the medicine aspect of the content that reduces T-CHOL in the serum and/or low-density lipoprotein cholesterol.
Present oligochitosan product generally is to distinguish by the distribution of its number-average molecular weight.
Preferably, described oligochitosan is that number-average molecular weight is not more than 1000 oligochitosan or number-average molecular weight and is not more than 3000 oligochitosan or number-average molecular weight and is not more than 5000 oligochitosan.
More preferably, described oligochitosan is that number-average molecular weight is not more than 1000 oligochitosan or number-average molecular weight and is not more than 3000 oligochitosan.
Preferably, number-average molecular weight is not more than 1000 oligochitosan with the dosage of 1000 mg/Kg or 250 mg/Kg, number-average molecular weight is not more than 3000 oligochitosan with the dosage of 250 ~ 1000 mg/Kg, number-average molecular weight be not more than 5000 oligochitosan with the dose application of 1000 mg/Kg in the medicine aspect of preparation control body weight.
More preferably, number-average molecular weight is not more than 1000 oligochitosan and is applied to prepare the medicine aspect of controlling body weight with the high dose of 1000 mg/Kg.Select this oligochitosan and select such dosage, the most pronounced effects of its control volume heavy prescription face, and effect is better than the product of existing control body weight.
More preferably, number-average molecular weight is not more than 3000 oligochitosan and is applied to prepare the medicine aspect of controlling body weight with the high dose of 1000 mg/Kg.Select this oligochitosan and select such dosage, it can be under the prerequisite that does not affect appetite, the control body weight, and can reduce body fat ratio simultaneously.
Preferably, be described number-average molecular weight be not more than 1000 oligochitosan with among 250～1000 mg/Kg or high dose be applied to prepare the medicine aspect of the content that reduces T-CHOL in the serum and/or low-density lipoprotein cholesterol.
Preferably, be that the oligochitosan of number-average molecular weight little 3000 is reduced the medicine of total cholesterol level in the serum with the dose application of 500 ~ 1000 mg/Kg in preparation; Or the oligochitosan of number-average molecular weight little 3000 is reduced the medicine of the content of serum low-density LP cholesterol in preparation with the dose application of 250 ~ 1000mg/Kg.
Preferably, be to be not more than 3000 oligochitosan to be applied to prepare the medicine aspect that reduces body fat with the high dose of 1000 mg/Kg with number-average molecular weight.
The further research summary of the present invention obtains, middle dosage (500 mg/Kg), the number-average molecular weight that number-average molecular weight is not more than 1000 oligochitosan be not more than high dose (1000mg/Kg) and the low dosage (250 mg/Kg) of 3000 oligochitosan can significant blood sugar lowering level.Therefore,
Preferably, to be not more than middle dosage (500 mg/Kg), the number-average molecular weight of 1000 oligochitosan be to be not more than the high dose (1000 mg/Kg) of 3000 oligochitosan and the medicine aspect that low dosage (250 mg/Kg) is applied to prepare blood sugar lowering to number-average molecular weight.
The further research summary of the present invention obtains; it is to be not more than the metabolism that 3000 oligochitosan can accelerate liver fat that number-average molecular weight is not more than 1000 oligochitosan and number-average molecular weight; reduce fat in the deposition of liver; liver had protective effect; can both improve hepatocellular necrosis, number-average molecular weight is that to be not more than low dosage (250 mg/Kg) effect of 3000 oligochitosan more obvious.
The invention has the beneficial effects as follows:
Although the oligochitosan molecular weight ranges is little, but, the present invention sums up through the lot of experiments binding analysis, in close relations between the molecular weight of oligochitosan and the application technology effect, but machine-processed unclear, the physiological disposition of oligochitosan, mechanism of action the unknown, difficult quality control causes the drug effect poor repeatability, is restricting the application of oligochitosan always, especially aspect Weight-reducing and lipid-lowering, rarely seen technology is reported.Weight-lossing hypolipemic medicine market remains chemicalses such as using orlistat at present.
The invention provides the new application of oligochitosan, successful its is applied to preparation fat-reducing and/or fat-reducing medicament aspect, oligochitosan has fat-reducing and lipid-lowering effect, can also alleviate fatty liver simultaneously, blood fat in the minimizing serum.
The relation that the present invention is clear and definite between different number-average molecular weights and the Weight-reducing and lipid-lowering mechanism.For example, aspect appetite-suppressing, the effect of the oligochitosan of different number-average molecular weights is significantly different.For the application of oligochitosan provides strong technical know-how basis.
Description of drawings
Each medicine of Fig. 1 is on the figure that affects of liver form, and among the figure, the first row left-to-right is followed successively by Normal group, obese model group and orlistat group; The second row left-to-right is followed successively by COS1-H, COS1-M, COS1-L group; The third line left-to-right is followed successively by COS2-H, COS2-M, COS2-L group;
Fig. 2 uses the hepatic pathology slice map behind each medicine, and among the figure, the first row left-to-right is followed successively by Normal group, obese model group and orlistat group; The second row left-to-right is followed successively by COS1-H, COS1-M, COS1-L group; The third line left-to-right is followed successively by COS2-H, COS2-M, COS2-L group;
Fig. 3 uses the heart pathology slice map behind each medicine, and among the figure, the first row left-to-right is followed successively by Normal group, obese model group and orlistat group; The second row left-to-right is followed successively by COS1-H, COS1-M, COS1-L group; The third line left-to-right is followed successively by COS2-H, COS2-M, COS2-L group;
Fig. 4 uses the mesentery fat pathological section figure behind each medicine, and among the figure, the first row left-to-right is followed successively by Normal group, obese model group and orlistat group; The second row left-to-right is followed successively by COS1-H, COS1-M, COS1-L group; The third line left-to-right is followed successively by COS2-H, COS2-M, COS2-L group;
Fig. 5 uses the subcutaneous fat pathological section figure behind each medicine, and among the figure, the first row left-to-right is followed successively by Normal group, obese model group and orlistat group; The second row left-to-right is followed successively by COS1-H, COS1-M, COS1-L group; The third line left-to-right is followed successively by COS2-H, COS2-M, COS2-L group.
The specific embodiment
Further describe the present invention below in conjunction with the drawings and specific embodiments.For convenience of description, raw material and material that the present invention adopts have illustrated respectively purchase producer, but therefore do not limit the scope of the invention.
Embodiment 1
1 materials and methods
1.1 test sample
Oligochitosan (Laizhou, Shandong sea Lik-Sang Tetramune company limited, COS1 number-average molecular weight≤1000, product batch number HL120916G; COS2 number-average molecular weight≤3000, product batch number HL120911G; COS3 number-average molecular weight≤5000, product batch number HL120907G).
1.2 laboratory animal
(credit number: SCXK(Guangdong) 2008-0002), body weight 70～90g buys in Guangdong Medical Lab Animal Center 185 of the male Sprague Dawley of SPF level rats, and adaptability is fed a week.
1.3 reagent and instrument
Orlistat capsule (Chongqing Watson Pharmaceutical Co., Ltd); Kit for determining alanine aminopherase (ALT), aspartate amino transferase are measured test kit (AST), triglyceride determination test kit (TG), T-CHOL mensuration test kit (CHO), determine cholesterol with high density lipoprotein test kit (HDL-C), low-density lipoprotein cholesterol mensuration test kit (LDL-C), glucose assays test kit (Glu) (Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.); Superoxide dismutase (SOD) WST-1 method testing cassete, protein quantification (Coomassie brilliant blue method) testing cassete (bio-engineering research institute is built up in Nanjing); Automatic clinical chemistry analyzer (AMS-18); Multi-functional microplate reader (Mithras LB 940); Germany's Zeiss inverted fluorescence microscope (AX10); Ai Bende miniature high-speed refrigerated centrifuger (Centrifuge 5418).
1.4 animal model
Select 185 of the SD rats of SPF level, single sex (male), it is 22 ± 1 ℃ in temperature, relative humidity is that adaptability is fed a week under 50～60% the environment, then laundering period is divided into two groups with it after finishing at random, and 20 rats give normal feedstuff as normal group, 5 in the remaining every cage of rat gives high lipid food.After feeding for 2 weeks, the rat that gives high lipid food is sorted by weight gain, eliminates 1/3 less fat opposing rat of weight gain.Give high lipid food 6 weeks the fat responsive type rat that filters out again, set up the nutritive obesity in rats model, the blank group gives normal feedstuff simultaneously.
Experiment high lipid food prescription: normal diet 54%, Adeps Sus domestica 15%, sucrose 15%, milk powder 4%, Semen arachidis hypogaeae 3%, yolk powder 5%, Oleum Sesami 1%, Sal 2%, calcium hydrogen phosphate 0.6%, stone powder 0.4%.
Modeling result's judgement: the rat body weight that high-calorie feed is fed exceeds the rat body weight 20% that normal diet is fed, the modeling success.
1.5 animal grouping
Choose fat Sensitive Rats by the body weight random packet, be respectively obese model group, orlistat group, COS1, COS2, high, medium and low three the dosage groups of COS3, add normal group, the laboratory animal grouping is totally 12 groups.
1.6 medication
After the modeling success, each administration group gives the given the test agent of various dose.The COS of variant molecular weight represents with H by 1000mg/Kg(), 500mg/Kg(represents with M), 250mg/Kg (representing with L) advances gavage; The orlistat group gives 2 times with respect to human dose, and the oral recommended dose 0.36g/ of orlistat human body days, then rat dosage was 37.5mg/Kg, therefore 2 times of rat oral gavage orlistat dosage are 75mg/Kg.Every group is carried out gavage by the 1mL/100g body weight, and fat group and blank group give isopyknic distilled water, and administration time was 6 weeks.
1.7 index observing
1.7.1 fat index observing
Every day entry rats eating amount during the administration, whether appetite, stool, urine amount, drinking-water, fur, activity, spirit, eyes, the heart beating of observing rat be normal.Regularly weigh in 1 time weekly, measure body long, then calculate Lee ' s index.Dissect rat, get perinephric fat, testis fat on every side, and weigh, namely the fat pad weight in wet base is calculated body fat ratio; Take out heart, liver, claim its weight in wet base, calculate the organ index ratio of body weight (each internal organs weight in wet base with).
1.7.2 blood parameters is observed
After experiment finished, fasting 16h weighed.Then use 1% pentobarbital sodium (0.5ml/100g BW) anesthesia, the ventral aorta blood sampling is left standstill 10 min, 3500 rmin
-1, centrifugal 15 min, separation of serum is surveyed the level of serum TC, TG, LDL-C, HDL-C, AST, ALT, GLu with automatic clinical chemistry analyzer by kit method, and microplate reader is surveyed serum and liver SOD.
1.7.3 pathology section examination
Get right lobe of liver, heart, mesentery fat, subcutaneus adipose tissue part, clean with normal saline, put into embedded box formaldehyde and fix, then after the different concentration ethanol dehydration, carry out embedding with paraffin, then cut into slices at microtome, THICKNESS CONTROL is floated sheet about 4 μ m, (43 ℃ of baking sheets, 20 min), then use haematoxylin-Yihong (HE) to dye, use the neutral gum mounting, under 200 times of visuals field of microscope, observe.
1.8 statistical method
Above experimental data is processed through the SPSS16.0 statistical software, and experimental result adopts means ± SD to represent, uses the comparison that One-Way ANOVA carries out many group sample averages, and P＜0.05 expression has statistical significance.
2 interpretations of result
2.1 the impact on fat index
2.1.1 the variation of rats eating amount
Every day entry rat is calculated the food-intake of rat to appetite, berley amount, surplus appetite during the administration.The food-intake of rat during administration is as shown in table 1:
Each administration group of table 1 is on the impact of food-intake (means ± SD)
Annotate: compare * P＜0.05, * * P＜0.01 with the obese model group.Compare with the orlistat group
△P＜0.05,
△ △P＜0.01.
As shown in Table 1, compare with the obese model group, the appetite of Normal group is better, and significant difference is larger, its P＜0.01, and except the COS1 high dose group, the appetite of other administration groups all is not affected.But with the orlistat positive drug relatively, among COS1 and the COS2, the still to some extent decline of low dose group appetite.COS2, COS3 and obese model group be the food-intake there was no significant difference relatively.
The result of table 1 shows: among the COS1, low dosage, and COS2, COS3 is on the not impact of appetite of rat, therefore its fat-reducing mechanism is not limited to the appetite that reduces rat.
2.1.2 the variation of rat body weight weightening finish and Lee ' s index
The body weight of weighing rat before and after the administration, and measure weekly the rat nose to the length at anus place, namely body is long, then calculates the Lee's index, and the result is as shown in table 2:
Each administration group of table 2 is on the impact of rat body weight and Lee's index (means ± SD)
Annotate: compare * P＜0.05, * * P＜0.01 with the obese model group.Compare with the orlistat group
△P＜0.05,
△ △P＜0.01.
As shown in Table 2, significant difference has appearred in the body weight of each administration group and obese model group rat body weight and rats in normal control group before the administration, P＜0.01, modeling success.After administration finished, there were significant difference in the body weight of orlistat group, COS1 high dose group and obese model group in the administration group, P＜0.05; From weight gain, each administration group rat body weight is compared the obese model group all reduction, and weight gain is less, COS1 high (P＜0.01), low dosage (P＜0.05), COS2(P＜0.05) high, normal, basic dosage, significant difference all appears in COS3 high dose (P＜0.05); Significant difference does not appear in the Lee's index of each administration group rat.
The result of table 2 shows: the COS1 high and low dose, the high, medium and low dosage of COS2, the COS3 high dose can well suppress the body weight of rat, wherein the effect of COS1 high dose reduction body weight has surpassed orlistat, the COS1 high dose is better than COS2 high dose and COS3 high dose, and the larger reduction body weight of COS dosage effect is better.
2.1.3 the variation of Rats Organs and Tissues index
After administration finishes, dissect rat, dirty, the liver of coring, and calculate organ index, and observing administration to the impact of lipidosis situation in heart and the liver, the result is as shown in table 3:
As shown in Table 3, cardiac index and the obese model group of each group relatively do not have significant difference, and the difference of liver index is larger, and obese model group liver index is larger, and the symptom of fatty liver is described.COS1 high (P＜0.05), in (P＜0.01), low dose group (P＜0.05), COS2 high (P＜0.05), low dose group (P＜0.01), relatively there are significant difference in liver index and the obese model group of COS3 high dose group (P＜0.05).
The result of table 3 shows: COS1 and COS2 can be good at reducing the deposition of liver fat, and effect is better than orlistat.It is better that COS3 only has high dose to reduce the effect of deposition of liver fat.
Each administration group of table 3 is on the impact of Rats Organs and Tissues index (means ± SD)
Annotate: compare * P＜0.05, * * P＜0.01 with the obese model group.Compare with the orlistat group
△P＜0.05,
△ △P＜0.01.
2.1.4 the variation of rat fat pad and body fat ratio
After administration finishes, dissect rat, get testis week, perirenal fat, calculate fat pad weight in wet base and body fat ratio, observe each medicine to the impact of rat body fat, the result is as shown in table 4:
As shown in Table 4, the rat fat pad weight in wet base of feeding high lipid food illustrates that greater than the fat pad weight in wet base of feeding normal feedstuff rat the fat content of high lipid food is more.Compare with the obese model group, orlistat, COS2 high dose can both well reduce the body fat of obese rat.And body fat is than COS2 high dose＜orlistat.COS3 fat pad content is higher, and is relatively poor for the effect that reduces rat body fat.
The result of table 4 shows: the COS2 high dose can be good at reducing the body fat of obese rat, and the effect that the presentation of results COS2 high dose of body fat ratio reduces body fat is better than orlistat.
Each administration group of table 4 is on the impact of rat fat pad and body fat ratio (means ± SD)
Annotate: compare * P＜0.05, * * P＜0.01 with the obese model group.Compare with the orlistat group
△P＜0.05,
△ △P＜0.01.
2.2 the impact on blood parameters
2.2.1 the variation of rat fat
The blood lipids index result that serum is measured at full automatic biochemical apparatus with test kit is as shown in table 5:
Each administration group of table 5 is on the impact of rat fat (means ± SD)
Annotate: compare * P＜0.05, * * P＜0.01 with the obese model group.Compare with the orlistat group
△P＜0.05,
△ △P＜0.01.
As shown in Table 5, with the obese model group relatively, COS1(P＜0.01) each dosage group, among the COS2, the high dose group (P＜0.05) of low dosage (P＜0.01) and COS3 can significantly reduce CHO, has statistical significance, effect all is better than orlistat.Compare with the obese model group, dosage can significantly reduce TG(P＜0.01 among the COS1), compare with the orlistat group, low dosage among the COS1, the high, normal, basic dosage of COS2 and COS3 high dose can significantly reduce TG.The HDL-C of COS1 high dose, COS2 low dosage reduces than significance with the obese model group, and the HDL-C significance of high, the middle dosage of COS2 and COS3 high dose raises, and reason is uncertain.COS1, COS2, COS3 compare the obese model group and can significance reduce LDL-C(P＜0.01).
The result of table 5 shows: COS1 and COS2 are larger on the impact of CHO and LDL-C, can be good at reducing the content of CHO and LDL-C in the serum, and effect are better than orlistat; And senior middle school's dosage of COS1 is better than senior middle school's dosage of COS2.COS3 also can fine reduction serum in the content of LDL-C, effect slightly is better than orlistat.
2.2.2 the variation of rat blood sugar
The blood lipids index result that blood is measured at full automatic biochemical apparatus with test kit is as shown in table 6:
Each administration group of table 6 is on the impact of rat blood sugar (means ± SD)
Annotate: compare * P＜0.05, * * P＜0.01 with the obese model group.Compare with the orlistat group
△P＜0.05,
△ △P＜0.01.
As shown in Table 6, compare the obese model group, dosage among the COS1 (P＜0.01), COS2 high dose (P＜0.05), low dosage (P＜0.05) and COS3 high dose (P＜0.05) can reduce the blood sugar level of obese rat significantly.
2.2.3 the variation of rats'liver AST and ALT
Glutamic oxaloacetic transaminase, GOT (AST) and glutamate pyruvate transaminase (ALT) are the important indicators that detect of liver function clinically, are used for judging whether liver is impaired, and the result that serum is measured at full automatic biochemical apparatus with test kit is as shown in table 7:
Each administration group of table 7 is on the impact of rats'liver AST and ALT (means ± SD)
Annotate: compare * P＜0.05, * * P＜0.01 with the obese model group.Compare with the orlistat group
△P＜0.05,
△ △P＜0.01.
As shown in Table 7, each medicine can both reduce the content of serum AST, but only has COS2 low dosage (P＜0.01) to have significant difference, and COS2 low dosage (P＜0.01) can significantly reduce Serum ALT content.
The result of table 7 shows: each medicine can both improve hepatocellular necrosis, and COS2 low dosage effect is more obvious.
2.2.4 the variation of rat blood serum regulating liver-QI SOD
Blood is measured serum regulating liver-QI superoxide dismutase SOD with test kit at full automatic biochemical apparatus, observes each medicine and removes free radical antioxidative effect, and the result is as shown in table 8:
Each administration group of table 8 is on the impact of rat blood serum regulating liver-QI SOD (means ± SD)
Annotate: compare * P＜0.05, * * P＜0.01 with the obese model group.Compare with the orlistat group
△P＜0.05,
△ △P＜0.01.
As shown in Table 8, compare the obese model group, the serum that each medicine increases and the value of liver SOD are less, do not have significant difference, and be meaningless.
The result of table 8 shows: COS1, COS2, COS3 are less on serum and liver SOD impact, its antiobesity action by anti peroxidation of lipid, remove free radical and do not prove effective.
2.3 liver anatomic observation and pathology section examination result
2.3.1 liver anatomic observation
Dissect rat, take out liver, observe the metamorphosis of liver, the result as shown in Figure 1: the Normal group liver volume is less, and color is darker, is cerise, clear-cut margin, tangent plane is smooth.The visible a large amount of fat granule of obese model group rat liver naked eyes, thus its colour changed into yellow, liver swelling, the edge is more blunt; Orlistat group liver is similar with Normal group on form, and fat granule slightly as seen.Each dosage group liver color of COS1 and COS2 is between front two classes, and the fatty liver symptom alleviates to some extent, shows that COS1 and COS2 can accelerate the metabolism of liver fat, reduces fat in the deposition of liver, and liver is had protective effect.
2.3.2 liver section is observed
The pathology of liver organization are cut into slices the result as shown in Figure 2: rats in normal control group liver cell clear in structure, and nucleus is larger, is arranged in the middle of the cell, and Cytoplasm is even, has no hepatocyte enlargement and steatosis.Obese model group rat hepatocytes serious swelling, out-of-shape, and with water sample variation and cell infiltration, visible fat vacuole not of uniform size squeezes nucleus in cell one side or nucleus and disappears in a large number in the cell, hepatocyte is fishing net shaped arranges, and belongs to and fills the air the fatty degeneration.The accidental cell cavity of each dosage group of COS1 and COS2, but compare the obese model group, the steatosis degree is lighter.
2.3.3 heart sections observation
Heart pathological section result is as shown in Figure 3: the Normal group myocardial cell is neat and orderly, and band is clear, and nucleus is without increase.Obese model group myocardial cell volume obviously increases, and the parts of fine karyon increases, cardiac muscle fiber arrangement disorder, interstitial fibers hypertrophy, visible inflammatory cell hypertrophy.After the administration, COS1, COS2 respectively organize myocardial cell and diminish, and nuclear has no increase, and band is clear, without cell infiltration.
2.3.4 mesentery fat sections observation
Mesentery adipose cell pathological section result is as shown in Figure 4: the Normal group adipose cell is less, and queueing discipline is tight, and the adipose cell of obese model group is larger, swelling occurs, and adipose cell is less under the identical multiple visual field.Except the COS2 low dose group, other dosage group adipose cells of COS1 and COS2 reduce, and the growth of adipose cell has obtained suppressing preferably.
2.3.5 subcutaneous film fat sections observation
Subcutaneous fat cells pathological section result is as shown in Figure 5: the Normal group subcutaneous fat cells is little, and cell number is many.And the subcutaneous fat cells of obese model group is larger, the swelling phenomenon occurs, and adipose cell is obviously less under the identical multiple visual field.Each dosed administration group subcutaneous fat cells of COS1 and COS2 reduces, and the growth of adipose cell has obtained preferably suppressing, and cellular morphology and orlistat group, normal group cell are similar.
Embodiment 2 toxicity tests
1 preliminary experiment
The NIH mice of SPF level, body weight are 18～22g, male and female half and half, and sub-cage rearing is 22 ± 1 ℃ in temperature, relative humidity is that adaptability was fed 3 days under 50～60% the environment, freely ingests, and drinks water and does not limit.(medicine is just smoothly by the gavage syringe needle to test the Cmax of using embodiment 1 described COS1 and COS2, and physicochemical property does not change) mice is carried out gavage, preliminary experiment arranges 3 dosage groups, being respectively 16g/Kg(once gives), 32g/Kg(gives for twice), 48g/Kg(gives for three times), 10 mices of each dosage group, male and female half and half.Before the administration, fasting 16h does not limit drinking-water, and each administration capacity is 0.2mL/10g, and each delivery time is 5h.
COS1 preliminary experiment result:
1.16g/Kg dosage: the mice mental status is normal, and diet drinking-water is normal, poisoning symptom do not occur.
2.32g/Kg dosage: the mice mental status is normal, and diet drinking-water is normal, poisoning symptom do not occur.
3.48g/Kg dosage: the mice mental status is normal, and diet drinking-water is normal, poisoning symptom do not occur.
COS2 preliminary experiment result:
1.16g/Kg dosage: the mice mental status is normal, and diet drinking-water is normal, poisoning symptom do not occur.
2.32g/Kg dosage: the mice mental status is normal, and diet drinking-water is normal, poisoning symptom do not occur.
3.48g/Kg dosage: the mice mental status is normal, and diet drinking-water is normal, poisoning symptom do not occur.
2 formally experiments
The NIH of SPF level, body weight is 18～22g, male and female half and half, sub-cage rearing is 22 ± 1 ℃ in temperature, relative humidity is that adaptability was fed 5d days under 50～60% the environment, freely ingests, and drinks water and does not limit.Experiment is divided into administration group and solvent matched group, every group of 10 mices, male and female half and half, (medicine is just smoothly by the gavage syringe needle with Cmax, and physicochemical property does not change) mice is carried out gavage, the administration group is gavage COS1 and COS2 respectively, and capacity is 0.3mL/10g, dosage is 24g/Kg, and the solvent matched group is filled with isopyknic distilled water.Before the administration, fasting 16h does not limit drinking-water.After finishing, gavage observes the poisoning symptom of mice, the body weight change of 2d, 7d, 14d behind the monitoring mouse stomach.
The COS1 experimental result:
The mice mental status is normal, and diet drinking-water is normal, poisoning symptom do not occur.According to acute toxicity (LD
50) the dosage hierarchical table, COS1 LD
50＞21g/Kg belongs to innocuous substance, and its maximum tolerated dose is greater than 24g/Kg.The result of its three weighing body weights is as shown in table 9:
Table 9 COS1 is on the impact of Mouse Weight (means ± SD)
As seen from table: mice all has increase in 2d, 7d, 14d body weight, and solvent matched group and administration group body weight amount of increase are more or less the same.
The COS2 experimental result:
The mice mental status is normal, and diet drinking-water is normal, poisoning symptom do not occur.According to acute toxicity (LD
50) the dosage hierarchical table, COS2 LD
50＞21g/Kg belongs to innocuous substance, and its maximum tolerated dose is greater than 24g/Kg.The result of its three weighing body weights is as shown in table 10:
Table 10 COS2 is on the impact of Mouse Weight (means ± SD)
As seen from table: mice all has increase in 2d, 7d, 14d body weight, and solvent matched group and administration group body weight amount of increase are more or less the same.
The present invention sums up through lot of experiments, and COS1 high and low dose and COS2 can significantly suppress the body weight of rat, and wherein the effect of COS1 high dose reduction body weight has surpassed orlistat.Simultaneously COS1 and COS2 can significantly reduce the deposition of liver fat, significantly reduce the content of CHO and LDL-C in the serum, and reduce that CHO and LDL-C effect are better than orlistat in the serum.
Claims (9)
1. the application of oligochitosan is characterized in that, is applied to prepare the medicine aspect of fat-reducing and/or blood fat reducing.
2. the according to claim 1 application of described oligochitosan is characterized in that, is applied to prepare the medicine aspect of controlling body weight.
3. application according to claim 1 is characterized in that, is applied to prepare the medicine aspect of the content that reduces T-CHOL in the serum and/or low-density lipoprotein cholesterol.
4. the application of the described oligochitosan of any one claim according to claim 1 ~ 3, it is characterized in that, described oligochitosan is that number-average molecular weight is not more than 1000 oligochitosan or number-average molecular weight and is not more than 3000 oligochitosan or number-average molecular weight and is not more than 5000 oligochitosan.
5. the according to claim 2 application of described oligochitosan, it is characterized in that, number-average molecular weight is not more than 1000 oligochitosan with the dosage of 1000 mg/Kg or 250 mg/Kg, number-average molecular weight is not more than 3000 oligochitosan with the dosage of 250 ~ 1000 mg/Kg, number-average molecular weight be not more than 5000 oligochitosan with the dose application of 1000 mg/Kg in the medicine aspect of preparation control body weight.
6. the according to claim 5 application of described oligochitosan is characterized in that, number-average molecular weight is not more than 1000 oligochitosan with the dose application of 1000 mg/Kg in the medicine aspect of preparation control body weight.
7. application according to claim 3, it is characterized in that, be that number-average molecular weight is not more than 1000 oligochitosan is to reduce the medicine aspect of the content of T-CHOL in the serum and/or low-density lipoprotein cholesterol with the dose application of 250～1000 mg/Kg in preparation.
8. application according to claim 3 is characterized in that, is the oligochitosan of number-average molecular weight little 3000 is reduced the medicine of total cholesterol level in the serum with the dose application of 500 ~ 1000 mg/Kg in preparation; Or the oligochitosan of number-average molecular weight little 3000 is reduced the medicine of the content of serum low-density LP cholesterol in preparation with the dose application of 250 ~ 1000mg/Kg.
9. the according to claim 1 application of described oligochitosan is characterized in that, number-average molecular weight is not more than 3000 oligochitosan reduces body fat in preparation with the dose application of 1000 mg/Kg medicine aspect.
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| CN104922143A (en) * | 2015-05-14 | 2015-09-23 | 福州乾正药业有限公司 | EGCG (epigallocatechin gallate) and chitosan oligosaccharide composition as well as preparation method and application thereof |
| CN105105137A (en) * | 2015-10-09 | 2015-12-02 | 福建师范大学 | Blueberry anthocyanin and chitosan oligosaccharide composition and preparation method thereof |
| CN109549950A (en) * | 2017-09-27 | 2019-04-02 | 天津大学 | Application of the chitosan oligosaccharide Biguanide derivative in preparation treatment disorders of lipid metabolism drug |
| WO2019227744A1 (en) * | 2018-06-01 | 2019-12-05 | 广东药科大学 | Chitosan oligosaccharide granules and preparation method therefor |
| CN111617030A (en) * | 2020-05-22 | 2020-09-04 | 广东药科大学 | Chitosan oligosaccharide oral liquid and application thereof in preparation of weight-reducing medicine |
| CN112608958A (en) * | 2020-12-17 | 2021-04-06 | 黄河三角洲京博化工研究院有限公司 | Chitosan oligosaccharide preparation method and weight-losing tablets |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104922143A (en) * | 2015-05-14 | 2015-09-23 | 福州乾正药业有限公司 | EGCG (epigallocatechin gallate) and chitosan oligosaccharide composition as well as preparation method and application thereof |
| CN105105137A (en) * | 2015-10-09 | 2015-12-02 | 福建师范大学 | Blueberry anthocyanin and chitosan oligosaccharide composition and preparation method thereof |
| CN109549950A (en) * | 2017-09-27 | 2019-04-02 | 天津大学 | Application of the chitosan oligosaccharide Biguanide derivative in preparation treatment disorders of lipid metabolism drug |
| WO2019227744A1 (en) * | 2018-06-01 | 2019-12-05 | 广东药科大学 | Chitosan oligosaccharide granules and preparation method therefor |
| CN111617030A (en) * | 2020-05-22 | 2020-09-04 | 广东药科大学 | Chitosan oligosaccharide oral liquid and application thereof in preparation of weight-reducing medicine |
| CN111617030B (en) * | 2020-05-22 | 2021-09-07 | 广东药科大学 | Chitosan oligosaccharide oral liquid and application thereof in preparation of weight-reducing medicine |
| CN112608958A (en) * | 2020-12-17 | 2021-04-06 | 黄河三角洲京博化工研究院有限公司 | Chitosan oligosaccharide preparation method and weight-losing tablets |
| CN112608958B (en) * | 2020-12-17 | 2022-12-02 | 黄河三角洲京博化工研究院有限公司 | Chitosan oligosaccharide preparation method and weight-losing tablets |
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