CN108578374A - A kind of chitosan oligosaccharide granule and preparation method thereof - Google Patents
A kind of chitosan oligosaccharide granule and preparation method thereof Download PDFInfo
- Publication number
- CN108578374A CN108578374A CN201810554014.6A CN201810554014A CN108578374A CN 108578374 A CN108578374 A CN 108578374A CN 201810554014 A CN201810554014 A CN 201810554014A CN 108578374 A CN108578374 A CN 108578374A
- Authority
- CN
- China
- Prior art keywords
- chitosan oligosaccharide
- granule
- povidone
- aspartame
- chitosan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to pharmaceutical technology fields, and in particular to a kind of chitosan oligosaccharide granule and preparation method thereof.Chitosan oligosaccharide granule of the present invention contains chitosan oligosaccharide, epimedium aglucone, povidone, aspartame, is prepared by the following method：Chitosan oligosaccharide, epimedium aglucone and aspartame are added in the povidone ethanol solution configured, are stirred evenly, by this granulating mixture finally to obtain the final product.Chitosan oligosaccharide granule of the present invention is convenient to take, and stability is high, in good taste, while preparation method is simple, process stabilizing, can be applicable.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of chitosan oligosaccharide granule and preparation method thereof.
Background technology
Chitosan oligosaccharide (chitosan oligosaccharides, COS) is the deacetylated catabolite of chitosan, not only
It is unique positively charged cationic basic amine group oligosaccharide or a kind of animal fiber element in nature.Chitosan oligosaccharide is easily
It is dissolved in water, bioavilability is preferable in human body, is substance a kind of safe and non-toxic and with abundant bioactive functions,
Include antitumor, reducing blood lipid, anti-oxidant, anti-inflammatory, neuroprotection etc..Kang NH et al. find, chitosan oligosaccharide and
The mixture of protamine can reduce the activity of pancreatic lipase, to adjust the lipid-metabolism in animal body；Ex vivo animal is real
Test the concentration for illustrating that the mixture can also reduce TG, TC and LDL-C in serum, improve the concentration of HDL-C, improve liver,
Lipid-metabolism in excrement, to reduce the risk of the diseases such as angiocarpy.Meanwhile having another studies have shown that chitosan oligosaccharide can reduce
The concentration of TC in hyperlipemia in mice serum, improves the concentration of HDL-C, also reduces the content of both AST and ALT in serum,
To slow down damage or the lesion of liver, the double action with lipid-loweringing and protect liver.
Invention content
Inventor has found that average molecular weight≤3000Da chitosan oligosaccharides (COSM) have excellent reducing weight and blood fat activity.In vivo
Studies have shown that COSM good water solubilities, bioavilability is high, effect of weight reducing and an Orlistat (currently the only OTC in the market
Slimming drugs) quite, blood fat reducing function and Simvastatin (currently used fat-reducing medicament) it is suitable.Meanwhile chitosan oligosaccharide molecular weight
Low, there is easy to absorb moisture, solution strong reducing property, exposure oxidation reaction easily to occur in air, and the shelf-life is shorter.Therefore, have
A kind of dosage form of necessity research and development is to improve the stability of chitosan oligosaccharide.Chitosan oligosaccharide particle (COSMG) is made in COSM by the present invention, to it
Preparation process studies, and establishes high-fat adiposity rat model, studies its anti-obesity activity.
For overcome the deficiencies in the prior art, the purpose of the present invention is to provide a kind of chitosan oligosaccharide granule, the present invention carries
The chitosan oligosaccharide tablet appearance of confession is bright and clean, while its active constituents of medicine content is high, and dissolving out capability is good, convenient to take, in good taste, reason
Change property to stablize, long shelf-life.
To achieve the goals above, technical scheme is as follows：
Chitosan oligosaccharide granule of the present invention, containing chitosan oligosaccharide, epimedium aglucone, povidone, aspartame, by as follows
Method is prepared：A certain amount of povidone is dissolved in appropriate absolute ethyl alcohol, is stirred, so that povidone is completely dissolved, gathered
Tie up ketone ethanol solution；It is molten that chitosan oligosaccharide, epimedium aglucone and aspartame are added to the povidone absolute ethyl alcohol configured
It in liquid, stirs evenly, dry finally by this granulating mixture, whole grain dispenses to obtain the final product.
The weight ratio of chitosan oligosaccharide granule as described above, chitosan oligosaccharide and epimedium aglucone is 50-100:1；Preferably, weight
Amount is than being 75:1.
The weight ratio of chitosan oligosaccharide granule as described above, povidone and chitosan oligosaccharide is 1:24-45；Preferably, weight ratio
It is 1:30.
The weight ratio of chitosan oligosaccharide granule as described above, aspartame and chitosan oligosaccharide is 1:150-160；Preferably, weight
Amount is than being 1:155.
Chitosan oligosaccharide granule as described above, a concentration of 1.5-4% of povidone ethanol solution, it is preferable that concentration
It is 3%.
Chitosan oligosaccharide granule as described above, chitosan oligosaccharide average molecular weight≤3000Da.
Quality standard research
1 character
This product is granule.Natural quality inspection through more batches of samples is brown to brown granular, and taste is slightly sweet,
Phenomena such as equal Uniform of grain, color and luster is consistent, the no moisture absorption, softening, caking.The result is shown in Figure 1.
2 granularities
Experimental method presses 2015 editions《Chinese Pharmacopoeia》The lower regulation of annex IC, grain graininess is measured using double sieve methods.It presses
Determining ratio of adjuvant is pelletized, and precision weighs three parts, every part of 30g of chitosan oligosaccharide granule, and weighed weight is individually positioned in one
In number sieve, No. five sieves are placed in lower section, and left and right is round-trip, level sieving, sieving side tapping sieve 3min.No.1 sieve can not be crossed by taking
Net and the bulky grain of No. five sieves can be crossed and fine powder (X), precision weigh its weight, calculate it and account for the percentage of total weight.It presses
It is tested according to method, grain graininess the results are shown in Table 1.
1 chitosan oligosaccharide granule granulometry result of table
By experimental result in table it is found that three parts of granule particle size ranges are less than 15%, meet between 7%-8%
States Pharmacopoeia specifications.3 meltings
Experimental method presses 2015 editions《Chinese Pharmacopoeia》The lower regulation of annex IC, three parts of particle for taking the present invention to obtain, every part 1
Bag (10g) adds 200mL hot water, quickly stirs 5min, observe at once respectively.It is tested in the method, observation particle dissolves
Situation.It the results are shown in Table 2.
2 particle melting of table investigates result
| Serial number | Melting |
| 1 | Particle all dissolves, no turbid phenomenon |
| 2 | Particle all dissolves, no turbid phenomenon |
| 3 | Particle all dissolves, no turbid phenomenon |
Obtained particle all dissolves known to experimental result in table, and no turbid phenomenon meets States Pharmacopoeia specifications.
4 determinations of moisture
It weighs about 1.0g chitosan oligosaccharide granule samples to be positioned on the pallet of infrared moisture meter, closes instrument lid,
Startup program.After the completion of drying program, the reading of instrumentation Display panel is sample moisture, is taken reading.As a result
It is shown in Table 3.
3 chitosan oligosaccharide granule determination of moisture of table
Obtained chitosan oligosaccharide granule average moisture content is 6.19% known to experimental result in table, is less than 10%, meets
It is required that.5 losss on drying
This law is suitable for by thermostabilization and the evaporable sample of moisture.Chitosan oligosaccharide granule sample is placed in identical item
It is dried to the flat measuring cup of constant weight under part, it is accurately weighed, in dry to constant weight at the specified temperature in baking oven." constant weight " is
Refer to the weight differential after chitosan oligosaccharide granule sample is dried twice in succession or is blazing in 0.3mg weight below.It dries to constant weight
Second and weigh for each time later and should all continue to carry out after drying 1 hour under prescribed conditions.Drying temperature is generally 105
℃.Loss on drying measurement result is shown in Table 4.
4 chitosan oligosaccharide granule loss on drying of table
As shown in Table 4, chitosan oligosaccharide granule loss on drying average value is 1.49%, is less than 2%, meets States Pharmacopoeia specifications.
6 assays
The foundation of 6.1 phenol sulfuric acid content measuring methods
Chitosan oligosaccharide granule can hydrolyze in acid condition as D- Glucosamines, have a reproducibility, therefore can be with
Utilize the content for the method indirect determination chitosan oligosaccharide granule for measuring reduced sugar.Phend-sulphuric acid principle is：Saccharide compound exists
The lower dehydration of concentrated sulfuric acid effect generates furfural, and condensation reaction then, which occurs, with phenol generates a kind of orange red compound, in 488nm waves
There is absorption maximum under length.Phend-sulphuric acid operates relative ease, and reproducible, accuracy is higher, while being also what pharmacopeia was included
The method for measuring carbohydrate, therefore select the content of phend-sulphuric acid measurement chitosan oligosaccharide granule.
The preparation of 6.2 solution
Phenol solution：100.0g phenol is taken, 0.05g sodium bicarbonates and 0.10g aluminium flakes, distillation is added to collect 182 DEG C of fractions and be
Phenol must be recrystallized.Recrystallization phenol 80.0g is weighed, adds 20.0g distilled water to get a concentration of 80% phenol solution, is protected from light
It is stored in refrigerator.It takes 80% phenol solution 37.5mL to be settled to the phenol solution that 500mL is configured to 6% before use, now matches existing
With paying attention to being protected from light.Aminoglucose hydrochloride standard solution：Precision weighs 1.2038g aminoglucose hydrochlorides, with distillation water dissolution
Constant volume is to 100mL to get the mother liquor of a concentration of 10mg/mL of Glucosamine.
Chitosan oligosaccharide granule solution to be measured：Precision weighs dry chitosan oligosaccharide granule, is arrived with distillation water dissolution and constant volume
100mL prepares certain density chitosan oligosaccharide granule solution to be measured.
The foundation of 6.3 standard curves
The accurate Glucosamine mother liquor for drawing certain volume, is made into a series of solution of concentration gradients, with a concentration of cross
Coordinate, absorbance are ordinate, draw standard curve.It the results are shown in Table 5 and Fig. 2.
5 GLC standard curve data of table
The measurement of 6.4 chitosan oligosaccharide granule sample sizes
It takes chitosan oligosaccharide granule solution 2.0mL to be measured in 25mL colorimetric cylinders, sequentially adds 6% recrystallization phenol solution
1.0mL, concentrated sulfuric acid 5.0mL, gently shakes up, and boiling water bath 45min measures absorbance after the reaction was complete under 488nm.By measured value
Calibration curve equation is substituted into be calculated.Measurement result is shown in Table 6.
6 chitosan oligosaccharide granule sample size of table measures
It is 93.64%, RSD 0.91% that experiment, which measures chitosan oligosaccharide granule average content, meets sets requirement.
6.5 precision test
It takes chitosan oligosaccharide granule solution 2mL to be measured in 25mL colorimetric cylinders, sequentially adds 5% recrystallization phenol solution
1ml, concentrated sulfuric acid 5mL, gently shakes up, boiling water bath 45min, after the reaction was complete under 488nm 6 absorbances of parallel determination.It calculates
Content, RSD values.Precision the results are shown in Table 7.
7 chitosan oligosaccharide granule sample precision of table
Interpretation of result：Under the measurement fixed condition, RSD values are less than 2%, show that this method precision is good.
7 study on the stability
It was solution to be measured that precision, which draws the chitosan oligosaccharide granule that lot number is 20170928, at 0,2,4,6,8,10,12 hour
It is interior to carry out assay using Phenol sulfuric acid procedure every two hours, calculate average value and RSD values.Measurement result is shown in Table 8.
8 chitosan oligosaccharide granule sample stability of table
Interpretation of result：Assay value stabilization of the chitosan oligosaccharide granule in 12 hours.Sample solution is from preparing to test
It can be generally fully completed in 12 hours.
8 reproducibility are investigated
Precision is weighed with a collection of 6 parts of test sample, using Phenol sulfuric acid procedure parallel determination content, calculates average value and RSD values.
It the results are shown in Table 9.
9 chitosan oligosaccharide granule sample reproducibility of table
As a result see analysis：The RSD values of measurement result are less than 2%, show that the method reproducibility is good.
9 sample recovery rates are investigated
Precision weighs 6 parts of the chitosan oligosaccharide granule sample of known content, quantitative standard substance is added thereto, measurement contains
Recovery of standard addition and RSD values are calculated after amount.
To measure chitosan oligosaccharide granule recovery of standard addition average value be 99.19%, RSD values is 0.78% for experiment, such as 10 institute of table
Show.The assay method accuracy is high known to result.
10 chitosan oligosaccharide granule recovery of standard addition of table is tested
10 experiment conclusions and discussion
The present invention mainly has studied the preparation of chitosan oligosaccharide granule.Since COSM chance water condensations are blocking, granulation can not be ground,
So controlling environment temperature at 20-25 DEG C, humidity≤40% is more satisfactory.Chitosan oligosaccharide granule uses absolute ethyl alcohol as wetting
Agent, using 3% PVP as binder.The equal Uniform of chitosan oligosaccharide granule particle, color and luster is consistent, and the no moisture absorption, softening, caking etc. are existing
As meeting pharmacopoeial requirements；Moisture is 6.19%, meets health food requirement；Using phend-sulphuric acid to chitosan oligosaccharide particle
Agent carries out assay, and chitosan oligosaccharide granule average content is 93.64%, RSD 0.91%, meets sets requirement.
Technical scheme of the present invention has the following advantages that：
1) it is fast, effective rapid to have the advantages that precursor dosage form absorbs.
2) convenient to take, stability is high, in good taste.
3) dustability, adhesion, aggregation, hygroscopicity etc. are smaller.
4) present invention discover that chitosan oligosaccharide has collaboration antiobesity action after adding a small amount of epimedium aglucone, and keep granule molten
Go out rapidly, while the stability of chitosan oligosaccharide granule can be effectively improved.
5) formula of chitosan oligosaccharide granule of the present invention is simple, raw material is easy to get, while preparation method is simple, process stabilizing, can
It promotes and applies.
Description of the drawings
Fig. 1 is the chitosan oligosaccharide granule outside drawing that the present invention is prepared.
Fig. 2 is the GLC canonical plottings that Phenol sulfuric acid procedure of the present invention measures chitosan oligosaccharide granule.
Specific implementation mode
The present invention is further described below by way of specific embodiment, but the embodiment does not limit this hair in any way
The range of bright patent protection.
Embodiment 1
| Chitosan oligosaccharide | 90g |
| Povidone | 2g |
| Epimedium aglucone | 0.9g |
| Aspartame | 0.6g |
| Absolute ethyl alcohol | 100g |
Preparation process：2g povidone is dissolved in 100g absolute ethyl alcohols, is stirred, so that povidone is completely dissolved, obtain poly- dimension
Ketone ethanol solution；90g chitosan oligosaccharides, 0.9g epimedium aglucones and 0.6g aspartames are added to the povidone that has configured without
It in hydrous ethanol solution, stirs evenly, finally by this granulating mixture, 50 DEG C of dryings, 14 mesh sieves, screening packs to obtain the final product.
Embodiment 2
| Chitosan oligosaccharide | 96g |
| Povidone | 4g |
| Epimedium aglucone | 1.92g |
| Aspartame | 0.6g |
| Absolute ethyl alcohol | 100g |
Preparation process：4g povidone is dissolved in 100g absolute ethyl alcohols, is stirred, so that povidone is completely dissolved, obtain poly- dimension
Ketone ethanol solution；96g chitosan oligosaccharides, 1.92g epimedium aglucones and 0.6g aspartames are added to the povidone configured
It in ethanol solution, stirs evenly, finally by this granulating mixture, 50 DEG C of dryings, 14 mesh sieves, screening packs to obtain the final product.
Embodiment 3
| Chitosan oligosaccharide | 93g |
| Povidone | 3.1g |
| Epimedium aglucone | 1.24g |
| Aspartame | 0.6g |
| Absolute ethyl alcohol | 100g |
Preparation process：3.1g povidone is dissolved in 100g absolute ethyl alcohols, is stirred, so that povidone is completely dissolved, gathered
Tie up ketone ethanol solution；93g chitosan oligosaccharides, 1.24g epimedium aglucones and 0.6g aspartames are added to the poly- dimension configured
It in ketone ethanol solution, stirs evenly, finally by this granulating mixture, 50 DEG C of dryings, 14 mesh sieves, screening, packaging is
.
Comparative example 1
| Chitosan oligosaccharide | 93g |
| Povidone | 3.1g |
| Epimedium aglucone | 1.24g |
| Aspartame | 0.6g |
| Distilled water | 100g |
Preparation method is the same as the embodiment of the present invention 3.
Comparative example 2
| Chitosan oligosaccharide | 93g |
| Povidone | 6g |
| Epimedium aglucone | 1.24g |
| Aspartame | 0.6g |
| Absolute ethyl alcohol | 100g |
Preparation method is the same as the embodiment of the present invention 3.
Comparative example 3
| Chitosan oligosaccharide | 93g |
| Povidone | 3.1g |
| Epimedium aglucone | 1.24g |
| Aspartame | 1.2g |
| Absolute ethyl alcohol | 100g |
Preparation method is the same as the embodiment of the present invention 3.
Comparative example 4
| Chitosan oligosaccharide | 93g |
| Povidone | 3.1g |
| Aspartame | 0.6g |
| Absolute ethyl alcohol | 100g |
Preparation method is the same as the embodiment of the present invention 3.
Verify the measurement of 1 chitosan oligosaccharide granule dissolution rate of the present invention of example
Dissolution determination takes 6, sample, according to Chinese Pharmacopoeia annex the second method of dissolution determination, with pH6.8 phosphate-buffereds
Liquid is dissolution medium, and volume 500ml, rotating speed 50r/min, 37 DEG C of temperature, when through 15 minutes, sampling measures its absorbance, limits
Degree is the 80% of labelled amount.Experimental result is shown in Table 11.
11 granule dissolution determination result of table
| Group | 5min dissolution rates (%) | 15min dissolution rates (%) |
| Embodiment 1 | 99.6 | 99.9 |
| Embodiment 2 | 99.6 | 99.9 |
| Embodiment 3 | 99.8 | 99.9 |
| Comparative example 1 | 72.5 | 92.4 |
| Comparative example 2 | 89.3 | 97.3 |
| Comparative example 3 | 82.4 | 96.2 |
| Comparative example 4 | 92.4 | 98.1 |
As can be known from Table 1, dissolution of the embodiment of the present invention is rapid；Comparative example 1, distilled water replace ethyl alcohol, dissolution worst；
Comparative example 2, increases the content of povidone, and the granule of preparation dissolves out slowly in phosphate；Comparative example 3, increase Ah
The amount of Si Patan dissolves out more of the invention slow；Comparative example 4 dissolves out more of the invention slow without addition epimedium aglucone.
Verify 2 chitosan oligosaccharide granule stability test of the present invention of example
With reference to《Chinese Pharmacopoeia》(version in 2010) two annex XIXC bulk pharmaceutical chemicals and pharmaceutical preparation stability test guidance are former
Then, accelerated test and stability test are carried out to chitosan oligosaccharide granule made from 1-3 of the embodiment of the present invention and comparative example 1-4.It examines
The project of examining includes appearance character, chitosan oligosaccharide content and related substance, and all investigation projects meet States Pharmacopoeia specifications and are then considered as qualifying,
There is one or more project not meet pharmacopoeial requirements and be then considered as to fail.It the results are shown in Table 12 and table 13.
12 chitosan oligosaccharide granule Acceleration study result of table
Note："+" indicates qualified；"-" indicates unqualified.
13 chitosan oligosaccharide granule long-term experiment result of table
Note："+" indicates qualified；"-" indicates unqualified.
By table 12 and table 13 it is found that the stable in physicochemical property of 1-3 chitosan oligosaccharide granules of the embodiment of the present invention, long shelf-life.
The chitosan oligosaccharide granule stability test prepared with 1-3 of the embodiment of the present invention by chitosan oligosaccharide granule prepared by comparative example 1-4
The stability of Comparative result, the chitosan oligosaccharide granule that the present invention is prepared is better than comparative example, and the shelf-life is longer, illustrates the present invention
Composition and proportioning it is reasonable, the stability of chitosan oligosaccharide granule can be effectively improved.
The pharmacodynamics test research that 1 chitosan oligosaccharide granule of the present invention of experimental example loses weight
1.1 experimental animal
Male rat is selected, at the end of the laundering period, weight 100 ± 10g, every group 10.
1.2 dosage are grouped and given the test agent gives the time
Experiment sets 6 groups altogether, respectively：
1) blank group
2) model group
3) orlistat group (positive group)
4) chitosan oligosaccharide granule high dose group
5) chitosan oligosaccharide granule middle dose group
6) chitosan oligosaccharide granule low dose group
7) 4 groups of comparative example
Chitosan oligosaccharide particle agent dose：High, medium and low dosage press respectively 12 times of human body recommended dose (6g/60kg), 6 times, 3
Times gastric infusion, i.e. 1200mg/kg.d, 600mg/kg.d, 300mg/kg.d.
4 groups of dosage of comparative example press 6 times of gastric infusions of human body recommended dose (6g/60kg), i.e. 600mg/kg.d.
Orlistat dosage：According to 2 times of administrations of human dose.Orlistat human oral's recommended doses are 0.36g/d,
The dosage for being converted into rat is 37.5mg/kg, so the dosage of 2 times of rat oral gavage is 75mg/kg.d.
Computational methods：Rat dosage=people's dosage/60*6.25
Every rat carries out gavage by 1mL/100g weight, and model control group and blank control group give isometric distillation
Water.Given the test agent is given the time and is at least given 6 weeks, is no more than 10 weeks.
1.3 high heat model feeds
15.0% sucrose, 15.0% lard, suitable casein, calcium monohydrogen phosphate, mountain flour etc. are added in maintaining feed.It removes
Outside crude fat, moisture, crude protein, crude fat, crude fibre, coarse ash, calcium, phosphorus, the calcium of model feed：Phosphorus is intended to reach maintenance
The national standard of feed.
1.4 experimental procedure
1.2.4.1 obese model method
1) laundering period：Rat feeding maintains feed to observe 5-7 days under barrier system.
2) the modeling phase：
After laundering period 2 groups are randomly divided by weight, 10 rats, which are given, maintains feed as blank control group, and 120
Rat gives high heat model feed.It records weekly to appetite, berley amount, surplus appetite, weighs in 1 time.
After feeding 2 weeks, 120 rats for giving high-calorie feed are sorted by weight gain, and it is lower to eliminate weight gain
Diet resistant rat.Give filter out 60 fat Sensitive Rats to high-calorie feed again 6 weeks, blank control group is given simultaneously
Maintain feed.
3) given the test agent is given：
After the modeling phase, 70 fat Sensitive Rats are randomly divided into 7 groups, respectively model control group, blank by weight
Control group, positive controls and 4 sample sets.Record is weighed in weekly 1 time to appetite, food ration, surplus appetite daily.Mould
Type control group, positive controls and 4 sample sets give high heat model feed, and blank control group gives maintenance feed.Respectively give
Medicine group gavage gives the given the test agent of various dose, and model control group and blank control group give the coordinative solvent of equivalent, tested
Sample gives the time 8 weeks, is no more than 10 weeks.Experimental result is shown in Table 14.
Influence (unit of the 14 different experiments group of table to mouse weight：g)
Note：Compared with model control group, * P<0.05；Compared with 4 groups of comparative example, △ is P ＜ 0.05.
As shown in Table 14, it weighed every 2 weeks the 2nd week after administration, the results show that since the 4th week, with model
Control group compares, three blank control group, orlistat group, 4 groups of comparative example and basic, normal, high dosage rats in test groups bodies
Weight is significantly lower than model control group (P<, and three test groups of basic, normal, high dosage and blank control group and Ao Lisi 0.05)
His group compares that there was no significant difference (P>0.05), and since the 6th week, chitosan oligosaccharide granule middle dose group and comparative example
4 groups of (the two dosage is identical) more significant difference (P<0.05), this illustrates that chitosan oligosaccharide is combined with epimedium aglucone and answers
There is good effect of weight reducing for obesity mice after, it can be confirmed that 2 kinds of substances in the present invention have significant association
Same effect, in three dosage, the function and effect of middle dose group are best.
Influence of the 2 chitosan oligosaccharide granule of the present invention of experimental example to obese rat Lee ' s indexes
Lee's indexes are similar with the body mass index BMI of people, main to reflect body obese degree.
Influence of the 15 different experiments group of table to obese rat Lee ' s indexes
| Group | Lee ' s indexes (before experiment starts) | Lee ' s indexes (after experiment) |
| Blank control group | 297.8* | 301.2* |
| Model control group | 322.7 | 318.4 |
| Orlistat group (positive group) | 321.4 | 301.3* |
| Chitosan oligosaccharide granule low dose group | 319.6 | 308.2* |
| Chitosan oligosaccharide granule middle dose group | 320.5 | 303.1*△ |
| Chitosan oligosaccharide granule high dose group | 320.1 | 306.7* |
| 4 groups of comparative example | 321.2 | 310.4* |
Note：Compared with model control group, * P<0.05
As shown in Table 15, blank control group, 4 groups of comparative example, orlistat group and basic, normal, high dose after experiment
Lee ' the s indexes for measuring three rats in test groups are significantly lower than model control group (P<, and basic, normal, high dosage three 0.05)
Difference there are no significant meaning (P between test group and between test group and blank control group and orlistat group>0.05), this
4 groups of (the two dosage is identical) more significant difference (P of outer chitosan oligosaccharide granule middle dose group and comparative example<
0.05), this illustrates that chitosan oligosaccharide has good effect of weight reducing with after epimedium aglucone use in conjunction for obesity mice, thus may be used
There is significant synergy, chitosan oligosaccharide granule middle dose group obesity index of the present invention with the 2 kinds of substances confirmed in the present invention
Improve statistically, high dose group low better than chitosan oligosaccharide granule.
Claims (8)
1. a kind of chitosan oligosaccharide granule, which is characterized in that containing chitosan oligosaccharide, epimedium aglucone, povidone, aspartame, by such as
Lower section method is prepared：A certain amount of povidone is dissolved in appropriate absolute ethyl alcohol, is stirred, so that povidone is completely dissolved, obtain
Povidone ethanol solution；Chitosan oligosaccharide, epimedium aglucone and aspartame are added to the povidone absolute ethyl alcohol configured
It in solution, stirs evenly, dry finally by this granulating mixture, whole grain dispenses to obtain the final product；The weight ratio of povidone and chitosan oligosaccharide
It is 1:24-45；The weight ratio of aspartame and chitosan oligosaccharide is 1:150-160.
2. chitosan oligosaccharide granule according to claim 1, which is characterized in that chitosan oligosaccharide and icariin in the granule
The weight ratio of member is 50-100:1.
3. chitosan oligosaccharide granule according to claim 1, which is characterized in that chitosan oligosaccharide and icariin in the granule
The weight ratio of member is 75:1.
4. chitosan oligosaccharide granule according to claim 1, which is characterized in that povidone and the weight ratio of chitosan oligosaccharide are 1:
30。
5. chitosan oligosaccharide granule according to claim 1, which is characterized in that aspartame and chitosan oligosaccharide 1:155.
6. chitosan oligosaccharide granule according to claim 1, which is characterized in that the povidone ethanol solution it is dense
Degree is 1.5-4%.
7. chitosan oligosaccharide granule according to claim 4, which is characterized in that the povidone ethanol solution it is dense
Degree is 3%.
8. chitosan oligosaccharide granule according to claim 1, which is characterized in that the chitosan oligosaccharide average molecular weight≤3000Da.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810554014.6A CN108578374B (en) | 2018-06-01 | 2018-06-01 | Chitosan oligosaccharide granules and preparation method thereof |
| PCT/CN2018/103511 WO2019227744A1 (en) | 2018-06-01 | 2018-08-31 | Chitosan oligosaccharide granules and preparation method therefor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810554014.6A CN108578374B (en) | 2018-06-01 | 2018-06-01 | Chitosan oligosaccharide granules and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108578374A true CN108578374A (en) | 2018-09-28 |
| CN108578374B CN108578374B (en) | 2020-04-03 |
Family
ID=63630583
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810554014.6A Active CN108578374B (en) | 2018-06-01 | 2018-06-01 | Chitosan oligosaccharide granules and preparation method thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN108578374B (en) |
| WO (1) | WO2019227744A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111875752A (en) * | 2020-08-18 | 2020-11-03 | 福建梁野山农业开发有限公司 | Nano-selenium composite material and preparation method thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103622946A (en) * | 2012-08-26 | 2014-03-12 | 鲁南制药集团股份有限公司 | Medical application of anhydroicaritin |
| CN104770641A (en) * | 2015-04-15 | 2015-07-15 | 威海御膳坊生物科技有限公司 | Ginkgo biloba extract compound preparation |
| CN104884066A (en) * | 2012-11-21 | 2015-09-02 | 株式会社爱茉莉太平洋 | Amylase-activity-inhibiting composition containing chito-oligosaccharide |
| 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 |
| CN105326053A (en) * | 2015-10-03 | 2016-02-17 | 王保红 | L-carnitine and chitosan oligosaccharide-containing composition and preparation method and application |
| CN105380924A (en) * | 2015-12-24 | 2016-03-09 | 广东药学院 | Chtiosnaoligosaccharide (COS) capsule and preparation method thereof |
| CN105496981A (en) * | 2015-12-24 | 2016-04-20 | 广东药学院 | Chitosan oligosaccharide tablets and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284000A (en) * | 2007-04-10 | 2008-10-15 | 殷正丰 | Therapeutic agents for adiposity or fatty liver |
| CN103316031B (en) * | 2013-05-08 | 2015-04-22 | 广东药学院 | Weight reduction and body fat reduction applications of chitosan oligosaccharide |
-
2018
- 2018-06-01 CN CN201810554014.6A patent/CN108578374B/en active Active
- 2018-08-31 WO PCT/CN2018/103511 patent/WO2019227744A1/en active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103622946A (en) * | 2012-08-26 | 2014-03-12 | 鲁南制药集团股份有限公司 | Medical application of anhydroicaritin |
| CN104884066A (en) * | 2012-11-21 | 2015-09-02 | 株式会社爱茉莉太平洋 | Amylase-activity-inhibiting composition containing chito-oligosaccharide |
| CN104770641A (en) * | 2015-04-15 | 2015-07-15 | 威海御膳坊生物科技有限公司 | Ginkgo biloba extract compound preparation |
| 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 |
| CN105326053A (en) * | 2015-10-03 | 2016-02-17 | 王保红 | L-carnitine and chitosan oligosaccharide-containing composition and preparation method and application |
| CN105380924A (en) * | 2015-12-24 | 2016-03-09 | 广东药学院 | Chtiosnaoligosaccharide (COS) capsule and preparation method thereof |
| CN105496981A (en) * | 2015-12-24 | 2016-04-20 | 广东药学院 | Chitosan oligosaccharide tablets and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 潘海涛: "COST颗粒体内降血脂活性与机制研究", 《广东药科大学硕士论文》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111875752A (en) * | 2020-08-18 | 2020-11-03 | 福建梁野山农业开发有限公司 | Nano-selenium composite material and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108578374B (en) | 2020-04-03 |
| WO2019227744A1 (en) | 2019-12-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1876040B (en) | Detection method of pharmaceutical composition for treating hepatitis | |
| CN101985644A (en) | Momordica charantia polypeptide, preparation method and application thereof | |
| CN1803180A (en) | Medicine composition and its preparation method and quality control method | |
| CN108578374A (en) | A kind of chitosan oligosaccharide granule and preparation method thereof | |
| CN101336986B (en) | Medicine composition detection method | |
| CN104383370A (en) | Jianqu and its preparation method and quality detection method | |
| CN110301640A (en) | Bitter buckwheat flavone dry powder and its preparation have auxiliary hyperglycemic function health care product purposes | |
| CN101352494B (en) | Children's granules for clearing heat and suppressing cough and preparation method thereof | |
| CN102526656B (en) | Medicament or health-care food composition for preventing or/and treating erythremia | |
| CN101897740A (en) | Glabrous sarcandra herb formula particle and preparation method thereof | |
| CN105145957B (en) | A kind of health-care herbal tea beverage improving oral ulcer and preparation method thereof and detection method | |
| CN102125583A (en) | Pediatric paracetamol, cow-bezoar and chlorphenamine maleate granules and quality control method thereof | |
| CN110772596B (en) | Compound Chinese medicine peach blossom extract and its preparation process and use as medicine for treating diabetic cardiomyopathy | |
| CN100542595C (en) | A kind of Chinese medicine composition and preparation method thereof and analytical method | |
| CN103134896A (en) | Detection method for Chinese materia medica preparation for treating chronic prostatitis | |
| CN110075179B (en) | Aconitum rupestris formula granules, preparation method and detection method thereof | |
| CN106940354B (en) | Diterpenoids from bulbus Prostratin and Pekinenin G efficient liquid-phase chromatography method in a kind of measure stir-baked RADIX EUPHORBIAE EBIACTEO-LATAE with vinegar | |
| CN110025741A (en) | Four wonderful cool blood granules of one kind and preparation method thereof | |
| CN101700367B (en) | Pharmaceutical composition for treating diseases of urinary system | |
| CN101347568A (en) | Formulation of yam pills and quality control method | |
| CN103698465A (en) | Quality detecting method of cyrtomium rhizome medical material and thin-layer plate special for cyrtomium rhizome | |
| CN113952304B (en) | Preparation method of lung-heat clearing and toxin expelling granule | |
| CN108478553A (en) | Based on the inflammatory conditions protective agents of blood vessel endothelium inflammatory damage and its application | |
| CN105001275A (en) | Alkaloid carbon-glycoside with antiviral activity and antibacterial activity and application thereof | |
| CN108245500A (en) | Royal jelly acid is preparing the purposes in treating the raised disease medicine of activity of adenosine deaminase |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |