CN111617030A - Chitosan oligosaccharide oral liquid and application thereof in preparation of weight-reducing medicine - Google Patents
Chitosan oligosaccharide oral liquid and application thereof in preparation of weight-reducing medicine Download PDFInfo
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Abstract
The invention relates to the technical field of oral liquid, and provides chitosan oligosaccharide oral liquid and application thereof in preparing weight-losing medicines, wherein the oral liquid comprises the following raw materials in parts by weight: 30-45 parts of chitosan oligosaccharide, 1-2 parts of preservative, 0.5-1.5 parts of buffering agent, 1-3 parts of flavoring agent and 5-8 parts of stabilizer. The chitosan oligosaccharide oral liquid prepared by the invention has the advantages of quick absorption, quick effect, safety, effectiveness, stable preparation, stable quality and curative effect, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of oral liquid, in particular to chitosan oligosaccharide oral liquid and application thereof in preparing weight-reducing medicines.
Background
Obesity refers to a condition of excess accumulation of body fat, especially triglycerides, due to a degree of significant overweight and an excessively thick fat layer. Excessive accumulation of fat in the body due to excessive food intake or altered metabolism of the body causes excessive weight gain and causes pathological, physiological changes or latency in the human body. The prevalence of obesity has increased worldwide over the past 50 years, reaching a pandemic. Obesity is a significant health challenge as it greatly increases the risk of type 2 diabetes, fatty liver, hypertension, myocardial infarction, stroke, dementia, osteoarthritis, obstructive sleep apnea and some cancers, thus leading to a reduction in quality of life and life expectancy and thus being a public health problem of global general concern.
Because obesity can cause serious health problems, prevention and treatment of obesity becomes an important subject of research in the medical community, and although the medical community generally considers that improving life style and reasonably eating and strengthening exercise are main measures for losing weight, the medical community also considers that the medical community can be the first choice for patients with excessive obesity who fail to achieve satisfactory control through reasonable diet and exercise treatment.
Since the end of the 19 th century, a large number of weight-reducing medicines are continuously marketed until now, but the problems of unstable curative effect, unknown effective components, difficulty in international marketing and the like generally exist. Although various chemical weight-reducing drugs used clinically have a certain curative effect, most of them have certain side effects.
Chitosan Oligosaccharide (COS) is the only cationic basic amino oligosaccharide with positive charge in nature, is animal cellulose, and has a molecular structural formula as follows:
chitosan oligosaccharide is small molecular oligosaccharide with amino group degraded by chitosan derived from shrimp and crab shell, and is sugar chain with polymerization degree of 2-20. Because the molecular mechanism contains a great number of active chemical groups such as amino, acetamido, hydroxyl and the like, the COS has good plasticity and a plurality of physiological activities, and has various beneficial biological activities, such as antibacterial, anti-inflammatory, antioxidant, lipid-lowering, antidiabetic, functions of accelerating the absorption of calcium and iron in vivo, reducing blood sugar, promoting the repair of joint tissues and the like, and chitosan oligosaccharide becomes a new functional oligosaccharide in the world.
The chitosan oligosaccharide is prepared by degrading chitin, has good water solubility, low viscosity, small molecular weight, easy absorption, utilization and degradability, but is easy to generate the phenomena of layering, turbidity, precipitation and the like in the production of a chitosan oligosaccharide preparation, so that the stability of the chitosan oligosaccharide preparation is poor, and therefore, a novel chitosan oligosaccharide preparation is developed, the technical problem of instability of the preparation is solved, the weight-losing effect is fully exerted, and the chitosan oligosaccharide preparation has great significance.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the chitosan oligosaccharide oral liquid which is quick to absorb, quick to take effect, safe and effective, stable in preparation, stable in quality and curative effect, suitable for industrial production and strict in preparation process.
In order to achieve the purpose, the invention provides the following technical scheme:
the chitosan oligosaccharide oral liquid comprises the following raw materials in parts by weight: 30-45 parts of chitosan oligosaccharide, 1-2 parts of preservative, 0.5-1.5 parts of buffering agent, 1-3 parts of flavoring agent and 5-8 parts of stabilizer.
Preferably, the stabilizer is at least one of L-fucose and sodium carboxymethyl cellulose.
More preferably, the stabilizer consists of L-fucose and sodium carboxymethyl cellulose, and the mass ratio of the L-fucose to the sodium carboxymethyl cellulose is 4: 1.
Preferably, the preservative is one or both of sodium benzoate and potassium sorbate.
Preferably, the buffer solution is one or two of citric acid-sodium citrate and glacial acetic acid.
Preferably, the pH value of the buffer solution adjusting oral liquid is 4.5-8.5.
Preferably, the flavoring agent is one or two of aspartame and xylitol.
The second purpose of the invention is to provide a preparation method of chitosan oligosaccharide oral liquid, which comprises the following steps: taking a proper amount of purified water, adding chitosan oligosaccharide, a preservative and a stabilizer according to the amount of a prescription, shaking in a constant-temperature air bath until complete dissolution and inclusion, adding a flavoring agent, and finally adding a buffering agent to adjust the pH value to 4.5-8.5.
Preferably, the pH is adjusted to 6.5.
The third purpose of the invention is to provide an application of chitosan oligosaccharide oral liquid in preparing weight-reducing medicines.
Sodium carboxymethylcellulose is a carboxymethylated derivative of cellulose, has hygroscopicity and emulsion stability, is easily dispersed in water to form a transparent colloidal solution, and is an excellent emulsifier. In the production process of the chitosan oligosaccharide preparation, due to the fact that the oral liquid is prone to layering, turbidity, precipitation and other phenomena in the long-time placing process, the inventor tries to add sodium carboxymethylcellulose into the chitosan oligosaccharide oral liquid, and finds that the stability of the chitosan oligosaccharide oral liquid is greatly enhanced in a short time, and the oral liquid is not prone to layering, turbidity, precipitation and other phenomena.
Through a large amount of research and exploration, the invention discovers that the L-fucose and the sodium carboxymethylcellulose are compounded, so that the chitosan oligosaccharide oral liquid does not have the wall hanging phenomenon, and the stability of the chitosan oligosaccharide oral liquid can be enhanced.
In the invention, the chitosan oligosaccharide with the number average molecular weight not more than 3000 is named as COSM, the chitosan oligosaccharide with the number average molecular weight not more than 1000 is named as COST, for the purpose of distinguishing, the oral liquid prepared by the COSM is COSM oral liquid, and the oral liquid prepared by the COST is COST oral liquid.
Compared with the prior art, the invention has the following beneficial effects:
1. the chitosan oligosaccharide oral liquid provided by the invention has the advantages of quick absorption, quick effect, safety, effectiveness, stable preparation, stable quality and curative effect, and is suitable for industrial production.
2. The chitosan oligosaccharide oral liquid provided by the invention is applied to weight-losing medicines, can obviously reduce the weight gain of high-fat feed diet induced obese C57BL/6 mice, and obviously reduce the high fat content and the fat/body ratio caused by high-fat diet;
3. the chitosan oligosaccharide oral liquid provided by the invention greatly improves the medication compliance of patients and increases the using population of the medicine.
Detailed Description
The present invention will be described in further detail with reference to examples.
Example 1 Chitosan oligosaccharide oral liquid of the invention
The formula is as follows:
| chitosan oligosaccharide | 30g |
| Sodium benzoate | 1g |
| Potassium sorbate | 0 |
| L-fucose | 4g |
| Sodium carboxymethylcellulose | 1g |
| Citric acid-sodium citrate | 0.5g |
| Glacial acetic acid | 0 |
| Aspartame | 1g |
| Xylitol, its preparation method and use | 0 |
The preparation method comprises the following steps: the method comprises the following steps: taking a proper amount of purified water, adding chitosan oligosaccharide, preservative, buffering agent and stabilizing agent according to the amount of the prescription, shaking in a constant-temperature air bath until complete dissolution and inclusion, adding flavoring agent, and finally adjusting the pH to 4.5.
Example 2 Chitosan oligosaccharide oral liquid of the invention
The formula is as follows:
| chitosan oligosaccharide | 35g |
| Sodium benzoate | 0.5g |
| Potassium sorbate | 0.5g |
| L-fucose | 4.8g |
| Sodium carboxymethylcellulose | 1.2g |
| Citric acid-sodium citrate | 1g |
| Glacial acetic acid | 0 |
| Aspartame | 0.5g |
| Xylitol, its preparation method and use | 0.5g |
The preparation method comprises the following steps: the method comprises the following steps: adding chitosan oligosaccharide, antiseptic, buffer and stabilizer into appropriate amount of purified water, shaking in constant temperature air bath until completely dissolving and clathrating, adding correctant, and adjusting pH to 5.5.
Example 3 Chitosan oligosaccharide oral liquid of the invention
The formula is as follows:
| chitosan oligosaccharide | 40g |
| Sodium benzoate | 1g |
| Potassium sorbate | 1g |
| L-fucose | 5.6g |
| Sodium carboxymethylcellulose | 1.4g |
| Citric acid-sodium citrate | 1g |
| Glacial acetic acid | 0 |
| Aspartame | 1g |
| Xylitol, its preparation method and use | 1g |
The preparation method comprises the following steps: the method comprises the following steps: adding appropriate amount of purified water, adding chitosan oligosaccharide, antiseptic, buffer and stabilizer according to the amount of the prescription, shaking in constant temperature air bath until completely dissolving and clathrating, adding correctant, and finally adjusting pH to 6.5.
Example 4 Chitosan oligosaccharide oral liquid of the invention
The formula is as follows:
the preparation method comprises the following steps: the method comprises the following steps: taking a proper amount of purified water, adding chitosan oligosaccharide, preservative, buffering agent and stabilizing agent according to the amount of the prescription, shaking in a constant-temperature air bath until complete dissolution and inclusion, adding flavoring agent, and finally adjusting the pH to 8.5.
Example 5 Chitosan oligosaccharide oral liquid of the invention
The formula is as follows:
| chitosan oligosaccharide | 38g |
| Sodium benzoate | 0.5g |
| Potassium sorbate | 1g |
| L-fucose | 4.8g |
| Sodium carboxymethylcellulose | 1.2g |
| Citric acid-sodium citrate | 1.5g |
| Glacial acetic acid | 0 |
| Aspartame | 1g |
| Xylitol, its preparation method and use | 0.5g |
The preparation method comprises the following steps: the method comprises the following steps: adding appropriate amount of purified water, adding chitosan oligosaccharide, antiseptic, buffer and stabilizer according to the amount of the prescription, shaking in constant temperature air bath until completely dissolving and clathrating, adding correctant, and finally adjusting pH to 6.5.
Comparative example 1 Chitosan oligosaccharide oral liquid of the invention
Comparative example 1 was compared to example 5 with the only difference that the formulation did not contain sodium carboxymethylcellulose and L-fucose and the other parameters were the same as in example 5.
Comparative example 2 Chitosan oligosaccharide oral liquid of the invention
Comparative example 2 was compared with example 5 except that no L-fucose was contained in the formulation and the other parameters were the same as in example 5.
Comparative example 3 Chitosan oligosaccharide oral liquid of the invention
Comparative example 3 compares to example 5 with the only difference that no sodium carboxymethyl cellulose was included in the formulation and the other parameters were the same as in example 5.
Test example I, stability test
The chitosan oligosaccharide oral liquid prepared in the examples 1 to 5 and the comparative examples 1 to 3 is placed at normal temperature (40 +/-2 ℃) for 3 months under the normal humidity (75 +/-5%), and whether the wall hanging phenomenon and the precipitation phenomenon occur in the oral liquid is observed on the 0 th day, the 30 th day, the 60 th day and the 180 th day. The results are shown in Table 1:
TABLE 1
| Group of | Day 0 | Day 30 | Day 60 | Day 180 |
| Example 1 | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging |
| Example 2 | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging |
| Example 3 | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging |
| Example 4 | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging |
| Example 5 | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging |
| Comparative example 1 | With precipitation | / | / | - |
| Comparative example 2 | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging | No sediment and wall hanging |
| Comparative example 3 | With precipitation | / | / | / |
According to table 1, the chitosan oligosaccharide oral liquid prepared in examples 1-5 still has no wall-hanging phenomenon after 180 days, and meanwhile, the chitosan oligosaccharide oral liquid also has no phenomena of layering, turbidity, precipitation and the like, and the chitosan oligosaccharide oral liquid prepared in comparative example 1 has phenomena of layering, turbidity, precipitation and the like on day 0, and the precipitation is serious; the chitosan oligosaccharide oral liquid prepared in the comparative example 2 (without adding L-fucose) has the phenomena of wall hanging and the like after one month, but is not easy to have the phenomena of layering, turbidity, precipitation and the like; the chitosan oligosaccharide oral liquid prepared in the comparative example 3 (without adding sodium carboxymethyl cellulose) has the phenomena of layering, turbidity, precipitation and the like on day 0, and the layering, turbidity and precipitation phenomena are serious, so that the technical problem that the chitosan oligosaccharide oral liquid is hung on the wall due to the addition of sodium carboxymethyl cellulose can be solved by the compounding of L-fucose and sodium carboxymethyl cellulose, the chitosan oligosaccharide oral liquid added with sodium carboxymethyl cellulose has no phenomena of layering, turbidity, precipitation and the like, and the stability of the chitosan oligosaccharide oral liquid is enhanced.
Test example II, measurement of content of COST oral liquid and COSM oral liquid
According to the method for measuring polysaccharide in Chinese pharmacopoeia (2015), the content of main drugs in COST oral liquid and COSM oral liquid is measured by a phenol-sulfuric acid method.
1.1 absorption Curve and glucosamine plotting: solution preparation: 80% phenol stock solution: weighing 8.00g of Phenol by using an electronic balance, heating and melting, and then putting the Phenol into a 10mL volumetric flask by using double distilled water to obtain 80% Phenol solution, and storing the Phenol solution at 4 ℃ in the dark for later use.
5% phenol solution: precisely sucking 625ul of 80% phenol stock solution by a pipette, and dissolving in a 10ml volumetric flask by using double distilled water to obtain 5% phenol stock solution which is prepared for use.
10mg/ml GLC (glucosamine hydrochloride) standard solution: 0.1049g of glucosamine hydrochloride is precisely weighed by a ten-thousandth electronic balance, and is dissolved into a 10ml volumetric flask by double distilled water, and the volume is constant, thus obtaining 10mg/ml GLC standard solution.
COST oral liquid and COSM oral liquid operating liquid: the oral liquid can be directly used.
Precisely sucking 0.4mL of 10mg/mL GLC standard solution, and placing the solution in a 10mL volumetric flask to obtain solution A; taking 10mL test tubes, respectively and sequentially adding 1.0mL of 5% phenol solution and 5.0mL of concentrated sulfuric acid, adding 2mL of A solution into a standard tube, adding 2mL of double distilled water into a blank tube, taking the blank tube as a reference, scanning an absorption curve of the solution of the standard tube, measuring the maximum absorption wavelength, taking a blank reagent as the reference, dehydrating COS under the action of the concentrated sulfuric acid to form furfural, and then carrying out a condensation reaction with the phenol to generate a compound with the maximum absorption peak at 490nm, so that the measurement wavelength is selected to be 490nm in subsequent experiments.
Precisely sucking 10mg/mL GLC standard solution of 0mL, 0.1mL, 0.2mL, 0.3mL, 0.4mL, 0.5mL, 0.6mL, 0.7mL and 0.8mL, and respectively dissolving in 10mL volumetric flasks with double distilled water to obtain a series of gradient standard solutions; then precisely sucking 2.0mL of the solution into a 10mL test tube, respectively and sequentially adding 1.0mL of 5% phenol solution and 5.0mL of concentrated sulfuric acid, shaking up, carrying out boiling water bath for 30-45min, standing and cooling; after the reaction is completed, the absorbance of the mixture is measured at 490nm wavelength, and a standard curve is drawn.
1.2 precision test
Precisely sucking a proper amount of the same sample solution, continuously measuring the content for 6 times, and calculating the RSD value, wherein the RSD value is not more than 2.0%.
According to tables 2-1 and 2-2, the mean content of the COST oral liquid sample solution is 93.25%, the RSD is 1.59%, the mean content of the COSM oral liquid sample solution is 96.41%, and the RSD is 1.20%, which shows that the precision of the method is good.
TABLE 2-1 COST oral liquid precision test results
TABLE 2-2 COSM oral liquid precision test results
2.3 stability test
Precisely sucking the same sample solution, measuring the content in 0, 2, 4, 6, 8, 10 and 12h respectively, and calculating the RSD value, wherein the RSD value is not more than 2.0%.
According to tables 2-3 and 2-4, the average content of the COST oral liquid sample solution is 93.40%, the RSD is 1.11%, the average content of the COSM oral liquid sample solution is 96.36%, and the RSD is 1.70%, which indicates that the method is relatively stable.
TABLE 2-3 COST oral liquid stability test results
TABLE 2-4 COSM oral liquid stability test results
2.4 repeatability test
Precisely absorbing 6 parts of the same batch of sample solution, and measuring the content in parallel, wherein the RSD of the sample solution is not more than 2.0%.
According to tables 2-5 and tables 2-6, the average content of the COST oral liquid sample solution is 93.46%, the RSD is 1.76%, the average content of the COSM oral liquid sample solution is 96.28%, and the RSD is 1.65%, which shows that the method has good repeatability.
TABLE 2-5 COST oral liquid repeatability test results
TABLE 2-6 COSM oral liquid reconstitution test results
2.5 normalized recovery test
Precisely absorbing 6 parts of COS sample solution with known content, adding quantitative standard substance, measuring total content, calculating standard recovery rate, and its RSD should not be greater than 2.0%.
According to tables 2-7 and tables 2-8, the average recovery rate of the COST oral liquid sample solution is 100.01%, the RSD is 1.15%, the average recovery rate of the COSM oral liquid sample solution is 100.65%, and the RSD is 1.66%, which indicates that the method has high accuracy.
TABLE 2-7 COST oral liquid standard recovery test results
TABLE 2-8 COSM oral liquid standard recovery test results
2.6 quality inspection of COST oral liquid and COSM oral liquid
2.6.1 lightness examination
A20W fluorescent lamp is used as a light source, and a scattered shed type device is adopted. The background is a non-reflective black object and the bottom is a non-reflective white object. Placing the sterilized oral liquid under an inspection device, and comparing with black background and white background at a distance of 20cm from a light source. Visual inspection with naked eyes shows no visible insoluble substance or turbidity.
According to visual inspection, no insoluble substances or turbidity is found in the COST oral liquid and the COSM oral liquid.
2.6.2 microbial Limit tests
Unless otherwise specified, the microbial limit of the non-sterile product was checked: the microorganism counting method (rule 1105), the controlled bacteria examination method (rule 1106) and the non-sterile drug microorganism limit standard (rule 1107) are required to meet the regulations.
The total number of aerobic bacteria of the COST oral liquid and the COSM oral liquid is less than 1(cfu/ml), which meets the index; the total number of the mould and the microzyme is less than 1(cfu/ml), which meets the index; escherichia coli is not detected and meets the index; the salmonella is not detected and meets the index; the bile salt resistant gram-negative bacteria less than 10(cfu/ml) meets the index.
TABLE 2-9 COST oral liquid microbial limits
TABLE 2-10 COSM oral liquid microbial limits
2.6.3 content detection
And precisely absorbing 6 parts of sample solution by adopting a phenol-sulfuric acid method, and measuring the content in parallel, wherein the RSD of the sample solution is not more than 2.0%.
From tables 2-11 and tables 2-12, the COST oral liquid has an average content of 93.37% and an RSD of 1.72%. The average content of COSM oral liquid is 96.55%, and RSD is 1.45%.
TABLE 2-11 COST oral liquid content test results
TABLE 2-12 COSM oral liquid content test results
Third test example, study of fat-reducing and lipid-lowering experiment of Chitosan oligosaccharide oral liquid
1. Materials and methods
1.1 Experimental animals: SPF grade male C57BL/6 mice (Unit license number: SYXK (Yue) 2017-00125), ordered from Schleicklanda laboratory animals, Inc. in Hunan, 3-4 weeks old, sell Unit license number: SCXK (Xiang) 2016-0002. Orlistat capsules (purchased from Chongqing Baoyen pharmaceuticals, Inc.); d12492 high fat Diet (purchased from Research Diet, usa); the feed formula comprises the following components: casein, L-cystine, corn starch, maltodextrin, sucrose, cellulose, soybean oil, lard, compound minerals, calcium hydrophosphate, calcium carbonate, potassium citrate, compound vitamins, choline bitartrate and blue dye.
1.2 test apparatus
YB-6LF biological tissue paraffin embedding machine, YGQ-3126F biological tissue microtome (Sudoku medical electronic technology Co., Ltd., Xiaogan City); spectra Max i3x model multifunctional microplate reader (milar instruments (shanghai) ltd); total cholesterol (T-CHO) kit, Triglyceride (TG) kit, high density lipoprotein cholesterol (HDL-C) kit, low density lipoprotein cholesterol (LDL-C) kit, alanine Aminotransferase (ALT) kit, aspartate Aminotransferase (AST) kit, Free Fatty Acid (FFA) kit, Glucose (GLU) kit (tokyo institute of biotechnology); BCA protein concentration assay kit (pecan institute of biotechnology); Bio-Radbiorad electrophoresis apparatus (Boke scientific instruments, Inc., Shandong).
1.3 animal modeling
C57BL/6 mice were adaptively fed with a normal diet for 2 weeks in an SPF-class environment of experimental animals at a temperature of 24 + -2 deg.C, a relative humidity of 50% -60%, and an illumination rhythm of 12 hours, and then were randomly divided into two groups, wherein the C57BL/6 mice were fed with the normal diet, and the remaining C57BL/6 mice were fed with D12492 High fat diet (HFD, High fattier). After 2 weeks of feeding, D12492 high-fat diet-fed mice were ranked in order of high to low weight gain, and mice with less weight gain and obesity resistance were eliminated. The remaining C57BL/6 mice were maintained on high-fat diet for 6 weeks, while the normal diet group was given ordinary diet. When the weight of the mice fed with the high-fat feed exceeds 20% of the weight of the mice in the normal diet group, the success of the model building of the diet induced obesity model can be judged.
1.4 animal groups
The 10 mice on normal diet were blank (Control), and 70 obese mice successfully molded were randomly selected and randomly divided into seven groups (10 mice per group): the high fat Model group (Model), Orlistat positive control group (Orlistat), examples 1-5, for a total of 8 groups.
1.5 methods of administration
After the molding is successful, different doses of test samples are given to each administration group, and the blank group and the model group are subjected to intragastric lavage by the same amount of physiological saline. C57BL/6 mice were gavaged with the main doses of Orlistat (1700mg/Kg) and examples 1-5 (35mg/Kg), respectively, and C57BL/6 mice were gavaged with the dose of 0.lml per 10g of body weight. Each group was weighed at regular intervals weekly at C57 BL/6; the C57BL/6 was observed daily regularly for the presence or absence of abnormalities in mental state, physical signs and physiological state. The results are shown in Table 2.
TABLE 2 Effect of Chitosan oligosaccharide oral liquid on diet-induced obesity in mice
Note: p <0.05, P <0.01 compared to Control group; compared to the Model group, # P <0.05, # P < 0.01.
TABLE 3 Effect of Chitosan oligosaccharide oral liquid on fat in C57BL/6 obese mice
Note: p <0.05, P <0.01 compared to Control group; compared to the Model group, # P <0.05, # P < 0.01.
As can be seen from Table 2, after the molding was completed, the average body weight of the Control group was measured to be 24.29g, and the body weights of the C57BL/6 mice given high-fat diet were all over 31.18g, which was more than 20%, indicating that the molding was successful. At 8 weeks of administration, Orlistat and examples 1-5 were significantly lower than Model, indicating that diet-induced body weight was significantly reduced in each group. Compared with the Model group, the weight growth trend of the Orlistat group and the examples 1-5 is reduced.
As can be seen from Table 3, the fat pad and the fat/body ratio of the Control group are both significantly lower than the Model group; the Orlistat group had significantly lower fat pad and fat/body ratios than the Model group; the fat pads and the fat/body ratio were significantly reduced in the groups of examples 1 to 5 compared to the Model group, indicating that the high fat content and the fat/body ratio caused by the high fat diet were significantly reduced in all of the groups of examples 1 to 5.
The visceral adipose tissues were subjected to HE slice ice staining and observed. The fat cells in the Control group have normal structure, compact arrangement, uniform size, large number and small cell volume, while the white adipose tissue cells in the Model group have non-uniform size and large volume. After administration, the fat cells of the groups of examples 1 to 5 are obviously reduced compared with the fat cells of the Model group, the fat cells are uniform in size and small in size, and the pathological changes are better improved, which shows that the groups of examples 1 to 5 can inhibit fat cell hypertrophy induced by high fat diet, improve the growth and expansion of fat cells, reduce fat accumulation, and improve symptoms such as obesity.
The liver tissue was subjected to HE staining and sectioned, and observed. Liver lipid accumulation of mice in the Control group is little, liver lipid drops of mice in the Model group are more, and lipid accumulation is serious. The liver lipid droplet content and lipid droplet size of the mice in the groups 1-5 are obviously reduced compared with the Model group, and the lipid accumulation is improved.
The small intestine tissue was subjected to HE staining and sectioned, and observed. The villi of the small intestine of the mice in the Control group are high and neat, and the villi of the mice in the Model group are disordered, so that the intestinal barrier is seriously damaged, and the intestinal permeability is increased. The intestinal villi of the mice in the groups 1-5 are obviously tidy compared with the intestinal villi of the Model group, and the intestinal damage is improved.
The embodiments of the present invention are preferred embodiments of the present invention, and the scope of the present invention is not limited by these embodiments, so:
all equivalent changes made according to the structure, shape and principle of the invention are covered by the protection scope of the invention.
Claims (10)
1. The chitosan oligosaccharide oral liquid is characterized by comprising the following raw materials in parts by weight: 30-45 parts of chitosan oligosaccharide, 1-2 parts of preservative, 0.5-1.5 parts of buffering agent, 1-3 parts of flavoring agent and 5-8 parts of stabilizer.
2. The chitosan oligosaccharide oral liquid according to claim 1, wherein the stabilizer is at least one of L-fucose and sodium carboxymethyl cellulose.
3. The chitosan oligosaccharide oral liquid according to claim 1 or 2, wherein the stabilizer consists of L-fucose and sodium carboxymethyl cellulose, and the mass ratio of the L-fucose to the sodium carboxymethyl cellulose is 4: 1.
4. The chitosan oligosaccharide oral liquid according to claim 1, wherein the preservative is one or both of sodium benzoate and potassium sorbate.
5. The chitosan oligosaccharide oral liquid of claim 1, wherein the buffer solution is one or two of citric acid-sodium citrate and glacial acetic acid.
6. The chitosan oligosaccharide oral liquid according to claim 5, wherein the pH value of the oral liquid is adjusted to 4.5-8.5 by the buffer solution.
7. The chitosan oligosaccharide oral liquid of claim 1, wherein the flavoring agent is one or both of aspartame and xylitol.
8. The method for preparing chitosan oligosaccharide oral liquid according to claim 1, comprising the steps of: taking a proper amount of purified water, adding chitosan oligosaccharide, a preservative and a stabilizer according to the amount of a prescription, shaking in a constant-temperature air bath until complete dissolution and inclusion, adding a flavoring agent, and finally adding a buffering agent to adjust the pH value to 4.5-8.5.
9. The method for preparing chitosan oligosaccharide oral liquid according to claim 7, wherein said pH is adjusted to 6.5.
10. The application of the chitosan oligosaccharide oral liquid according to any one of claims 1 to 9 in preparing weight-reducing medicines.
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| PCT/CN2020/112801 WO2021232614A1 (en) | 2020-05-22 | 2020-09-01 | Chitooligosaccharide oral liquid and application therefor in preparation of weight loss drugs |
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