CN101103995B - Application of fly maggot chitosan in preparing product regulating blood sugar - Google Patents
Application of fly maggot chitosan in preparing product regulating blood sugar Download PDFInfo
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- CN101103995B CN101103995B CN2007102010366A CN200710201036A CN101103995B CN 101103995 B CN101103995 B CN 101103995B CN 2007102010366 A CN2007102010366 A CN 2007102010366A CN 200710201036 A CN200710201036 A CN 200710201036A CN 101103995 B CN101103995 B CN 101103995B
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Abstract
The invention discloses an application of flyblow chitosan in the preparation of a product for regulating blood-sugar, in particular to an application in the preparation of medicine or a health product for preventing or treating diabetes. Compared with the prior art, the flyblow chitosan used in the invention is prepared from flyblow chitin; the chitin contained in the skin of a flyblow is more than that contained in the shell of a shrimp or crab while the carbonate, heavy metal and coloring matter in the skin of the flyblow is less than that in the shell of the shell of the shrimp or crab, therefore the quality of the flyblow chistosan is far better than chitin in the shell of the shrimp or crab; the flyblow chitosan not only has the function of reducing blood-sugar and improving sugar tolerance, without influencing normal glycometabolism but also has the advantages of non-immunogenicity, degradation in an organism, non-toxicity, no-production of transformation reactions, mild immunologic stimulation and influence to the organism and easiness for preparation; thus the flyblow chitosan has good application prospect as the medicine or health product for regulating blood-sugar, preventing and treating diabetes.
Description
Technical field: the present invention relates to the application of fly maggot chitosan in the product of preparation blood sugar regulation, belong to insect resources and utilize technical field.
Background technology: diabetes are common incretion metabolism diseases of a kind of tool genetic predisposition, and hyperglycemia state is the main cause that causes chronic complicating diseases of diabetes, also do not have the medicine that can cure fully now.Therefore along with Chinese economic development, eating patterns constantly change, and domestic diabetics is increasing, seek determined curative effect, blood sugar lowering that toxic and side effects is little has become the important topic that various countries the world of medicine pays close attention to.
At occurring in nature, year biosynthesis amount of chitin is the second largest natural resources that is only second to plant cellulose up to hundred billion tons more than, also is the abundantest nitrogenous natural organic-compound of reserves on the earth.
Much studies show that, chitin take off acetyl product chitosan and derivant has biological activitys such as antioxidation, blood sugar lowering, the absorption of inhibition lipid, thereby can suppress the rising of blood glucose by number of ways, has the obvious functions of blood sugar effect, and it is safe, do not produce toxic and side effects, for the treatment diabetes have been opened up another approach.But in commercially available chitosan, great majority are raw material with shrimp, Carapax Eriocheir sinensis, and are that the feedstock production chitosan is very few with the fly larvae.Housefly is commonly referred to " fly ", and it has produced the distinctive anti-adversity ability of adverse circumstances by producing antibiotic substance such as lysozyme, antibacterial peptide, agglutinin, chitin etc. under the ecological pressure of long-term adverse circumstances.Therefore, the various compositions of research and utilization housefly are developed various products and are the mankind and environmental services thereof, become one of important directions of resource insect research.
Summary of the invention:
The objective of the invention is to: the application of fly maggot chitosan in the product of preparation blood sugar regulation is provided.The present invention is by setting up zoic model with hyperglycemia, fly maggot chitosan has been carried out hypoglycemic experimentation, and the hypoglycemic activity of the fly maggot chitosan of different deacetylations studied, for fly maggot chitosan is applied to medicine or field of health care products provides theoretical foundation better.
The present invention constitutes like this: the application of fly maggot chitosan in the product of preparation blood sugar regulation.
The application of fly maggot chitosan in the product of preparation prevention or treatment diabetes.
Above-described product is medicine or health product.
Specifically, fly maggot chitosan and pharmaceutical carrier or excipient are prepared into pharmaceutical preparation according to conventional method.
For example: get fly maggot chitosan, become 100～200 fine particle with the micropowder apparatus processing, add emulsifier for mixing and become suspension, send in the colloid mill and filter, the mud shape gel that obtains is sent into pill in the pellet processing machine, gets soft gelatin capsule; Get soft capsule with carrying out ungrease treatment after the soft gelatin capsule typing, send into again in the drying machine and get the finished product soft capsule through redrying.
Perhaps, add pharmaceutical carrier or excipient, be prepared into pharmaceutical preparation according to conventional method with fly maggot chitosan and the combination of other medicinal ingredient.
For example: get fly maggot chitosan 1000g, Fructus Momordicae charantiae 150g and Radix Puerariae 200g, pulverize, sieve, add appropriate amount of auxiliary materials, mixing, oven dry, sterilization, packing is made granule or capsule.
Can also with fly maggot chitosan separately or with other combinations of substances, be prepared into health product according to conventional method.
For example: get fly maggot chitosan, be dissolved in pH and be 3.5 hydrochloric acid or aqueous acetic acid, form gel, make slow release, controlled release preparation according to a conventional method.
Or get fly maggot chitosan 1000g and spirulina polysaccharide 200g, mixing is standby behind drying, porphyrize, mistake 100 mesh sieves respectively; Progressively increase method with aforementioned mixture and dextrin mixing with equivalent, add the abundant mixing of starch and microcrystalline Cellulose again, stir the alcoholic solution system soft material that spraying down adds 30% mass percent, granulate, cross 16 mesh sieves, 60 ℃ are dried to moisture and are about 5%, sieve, granulate, add Pulvis Talci, mix homogeneously, tabletting is made tablet.
Fly maggot chitosan of the present invention is to be raw material with the fly larvae chitin that Guizhou Kun'en Bioengineering Co., Ltd. provides, and adopts the soda acid chemical method to carry out deacetylation and makes.
Said medicine preparation or health product can be prepared into suitable administration form or the dosage form that can be used as human according to methods known in the art, route of administration can be intestinal or non-intestinal, as oral, muscle, subcutaneous, nasal cavity, oral mucosa, skin, peritoneum or rectum etc.Form of administration is tablet, capsule, drop pill, aerosol, pill, powder, solution, suspensoid, Emulsion, granule, liposome, transdermal agent, buccal tablet, inspection agent, unguentum etc. for example.Can be ordinary preparation, slow releasing preparation, controlled release preparation and various particulate delivery system.
When making tablet, can be extensive use of various carrier well known in the art: for example diluent and absorbent, as starch, dextrin, lactose, mannitol, sucrose, sodium chloride, glucose, carbamide, calcium carbonate, kaolin, microcrystalline Cellulose etc.; Wetting agent and binding agent are as water, glycerol, Polyethylene Glycol, ethanol, propanol, starch slurry, dextrin, syrup, Mel, glucose solution, mucialga of arabic gummy, gelatine size, sodium carboxymethyl cellulose, methylcellulose, polyvinylpyrrolidone etc.; Lubricant is as Pulvis Talci, corn starch, stearate, boric acid, liquid paraffin, Polyethylene Glycol etc.Tablet further can also be made coated tablet, for example sugar coated tablet, thin membrane coated tablet, ECT, or double-layer tablet, multilayer tablet.When making pill, can be extensive use of various carrier well known in the art: for example diluent and absorbent, as glucose, lactose, starch, nitrogenize vegetable oil, polyvinylpyrrolidone, Pulvis Talci etc.; Binding agent such as arabic gum, gelatin, ethanol, Mel, rice paste or batter etc.; Disintegrating agent is as dry starch, alginate, dodecyl sodium sulfate, methylcellulose, ethyl cellulose etc.In addition, can also add conventional cosolvent, buffer agent, pH regulator agent etc.As needs, also can in pharmaceutical preparation or health product, add coloring agent, antiseptic, spice, correctives, sweeting agent or other adjuvant.
Chitosan has the characteristic of dietary fiber, experiment confirm, and water-soluble fibre is better than the insoluble fibre blood sugar decreasing effect, and chitosan is better than water-soluble fibre.Chitosan is a gel at enteral, can reduce the dietary intake amount; Increase the intestinal juice viscosity, reduce the diffusion velocity of glucose to intestinal wall; The vigor that suppresses α-Dian Fenmei.The absolute deficiency of insulin or relative deficiency cause the improper metabolism of diabetics, make patient's body fluid be acid, improve sensitivity and utilization rate to insulin.After taking chitosan, can in gastrointestinal tract, form colloid, act on Insulin receptor INSR, make it strengthen sensitivity, suppress blood sugar increasing, improve glucose in urine, also can alleviate the stimulation of insulin secretion and the burden of β cell.Therefore, chitosan can be strengthened liver function, blood sugar regulation.In addition, chitosan also has certain treatment and preventive effect to diabetic complication.
In order to verify fly maggot chitosan at the action effect aspect the blood sugar regulation, the applicant has carried out animal model experiment, and is specific as follows:
1 material
1.1 the fly larvae chitin is provided by Guizhou Kun'en Bioengineering Co., Ltd..Fly maggot chitosan, self-control.
1.2 reagent sodium hydroxide: analytical pure, Shishewei Chemical Co., Ltd., Shanghai's product, lot number: 0501102.Hydrochloric acid: analytical pure, Zun Yi normal college's chemical reagent factory product, lot number: 20060629; Alloxan: U.S. SIGMA company product.
1.3 key instrument VERTEX70 infrared scanner, German BRUKER company; Abbott Laboratories' blood glucose meter, U.S.'s Abbott Laboratories company limited.
1.4 the animal Kunming mouse is male, 100, body weight 18～20g is provided by the Guiyang Medical College Experimental Animal Center.
2 experimental techniques
2.1 the preparation of experiment material and evaluation
2.1.1 the preparation of chitosan
Take by weighing three parts of fly larvae chitin 5.0g respectively, add NaOH and carry out deacetylation.React to the scheduled time, wash repeatedly to neutrality, dry, promptly get chitosan to constant weight with hot distilled water.
This experiment adopts acid-base method to prepare fly maggot chitosan, by controlling the chitosan that the different response time obtains different deacetylations.
2.1.2 Determination of deacetylating degree of chitosan
Adopt alkalimetry to measure the deacetylation of fly maggot chitosan.Accurately take by weighing 105 ℃ of sample 0.2g chitosans of drying to constant weight, place the 250ml triangular flask, add 0.1mol/L hydrochloric acid standard solution 30ml, be stirred to dissolving at 20 ℃～25 ℃ and (can add an amount of distilled water diluting too greatly) fully as if viscosity, add 2～3 mixed indicators (1%) methyl orange+(1%) aniline blue (1: 2), with 0.1mol/L standard solution of sodium hydroxide titration free hydrochloric acid.
Computational methods:
D.D％＝[(C
1V
1-C
2V
2)×0.016×100]/(G×9.94)
In the formula: C1--hydrochloric acid standard solution concentration (mol/L)
The volume (ml) of the salt standard acid solution that V1--adds
C2--standard solution of sodium hydroxide concentration (mol/L)
The standard solution of sodium hydroxide volume (ml) that consumes during the V2--titration
G---example weight (g)
0.016--the amine amount (g) suitable with 1ml 1mol/L hydrochloric acid solution
2.1.3 the infrared identification of different deacetylation chitosans
Chitosan is dried to constant weight,, surveys infrared spectrogram at 400-4000CM-1 with KBr mixed grinding, tabletting.
2.2 modeling and grouping
Behind the normal mouse fasting 14h (spending the night), intravenous injection 1% alloxan (50mg/kg normal saline solution), fasting glucose (getting the preceding fasting 8h of blood) is measured in the 72h eye socket venous plexus blood sampling of injection back.What blood glucose was higher than 11mmol/L is the hyperglycemia mice; According to blood glucose the hyperglycemia mice is divided into 5 groups at random, 14 every group, is respectively model control group, 3 chitosan group 200mg/kg (deacetylation is respectively 50%, 70%, 90%), positive controls (diabetes pill 1000mg/kg).Other gets 14 with criticizing normal mouse as the normal control group, gives the equal-volume distilled water.Gastric infusion, successive administration 14 days.
2.3 detection index
2.3.1 fasting glucose
After the administration 14 days, fasting 8 hours, blood glucose meter is measured fasting glucose.
2.3.2 carbohydrate tolerance:
Administration 14 days measure respectively organize the fasting blood sugar of mice after, measured carbohydrate tolerance in 15 days.Animal fasting administration after 7 hours, 1 hour lumbar injection gives glucose solution 2g/kg behind the medicine.After giving glucose 0,0.5,2h measures the blood glucose value of respectively organizing mice respectively.Observe model control group and the variation of area under each time point blood glucose curve after giving glucose of each dosage group of chitosan.
Area under the blood glucose curve=0.25 * (0h blood glucose value+4 * 0.5h blood glucose value+3 * 2h blood glucose value)
2.4 statistical procedures
All data are all represented with X ± S form, adopt t check carrying out statistical analysis.
3 experimental results
3.1 fly maggot chitosan sees Table 1 to the influence of mouse blood sugar:
Table 1 fly maggot chitosan is to the influence of mouse blood sugar (x ± s)
| Group | Dosage (mg/kg) | Blood glucose (mmol/L) before the medicine | Blood glucose behind the medicine (mmol/L) |
| The normal control group | -- | 8.2±0.6 | 8.1±0.3 |
| Model group | -- | 25.3±2.1 | 27.1±3.8 |
| The low deacetylation group | 300 | 25.2±2.7 | 19.9±3.5 |
| Middle deacetylation group | 300 | 25.6±2.2 | 16.2±1.4 ) |
| High deacetylized group | 300 | 26.5±2.3 | 11.9±2.5 ) |
Table 1 shows that each dosage group mice was taken fly maggot chitosan after 14 days, and the blood glucose value of diabetic mice all is lower than model control group (P＜0.01) due to the alloxan, shows that fly maggot chitosan has the fasting glucose effect that reduces the alloxan diabetes mice.
3.2 fly maggot chitosan sees Table 2 to the influence of mice carbohydrate tolerance:
Table 2 fly maggot chitosan is to the influence of mice carbohydrate tolerance (x ± s)
| Group | Dosage (mg/kg) | 0h blood glucose (mmol/L) | 0.5h blood glucose (mmol/L) | 2h blood glucose (mmol/L) | Area (mm under the blood glucose curve 2) |
| The normal control group | -- | 10.2±0.6 | 14.1±1.3 | 9.4±0.5 | 27.6±3.45 |
| Model group | -- | 25.3±2.1 | 33.2±2.1 2) | 24.4±2.3 | 57.2±4.32 |
| The low deacetylation group | 300 | 24.2±2.7 | 30.9±3.2 3) | 21.5±2.1 | 53.6±3.58 |
| Middle deacetylation group | 300 | 23.6±2.2 | 28.2±2.5 4)6) | 19.3±1.3 | 51.9±2.69 |
| High deacetylized group | 300 | 21.5±2.3 | 26.9±2.3 5)7) | 17.2±1.5 | 48.4±2.67 |
Table 2 shows that area all is starkly lower than model control group (P＜0.01) under each dosage fly maggot chitosan group blood glucose curve, shows that fly maggot chitosan has the carbohydrate tolerance effect that strengthens diabetic mice to some extent.
4 conclusions
This experiment shows the effect that fly maggot chitosan has blood sugar lowering and improves carbohydrate tolerance, does not influence normal carbohydrate metabolism again; Have and studies show that chitosan has the effect of the serum total cholesterol of remarkable reduction hyperlipemia rat, triacylglycerol, low-density lipoprotein cholesterol and the effect that improves the serum high-density LP cholesterol; Characteristics such as chitosan has non-immunogenicity again, can degrade in vivo.These natural special medical values will have certain application prospect aspect the diabetes preventing and treating.
The applicant has also carried out the acute toxicity zoopery to fly maggot chitosan, and dosage is by giving per kilogram rat 1200mg fly maggot chitosan every day, and the result shows the fly maggot chitosan avirulence, has the clinical practice meaning.
Compared with prior art, the used fly maggot chitosan of the present invention is got by the preparation of fly larvae chitin, and the chitin content in the maggot fur is higher than shrimp and crab shells, and carbonate and content of beary metal are low, pigment is few, and quality is much better than the chitin in the shrimp and crab shells; And the fly maggot chitosan effect that has blood sugar lowering and improve carbohydrate tolerance, do not influence normal carbohydrate metabolism again; Also have non-immunogenicity, can degrade in vivo and avirulence, do not produce allergy,, be convenient to characteristics such as preparation body immunostimulation influence as mild as a dove.Therefore fly maggot chitosan is having a good application prospect aspect blood sugar regulation, the medicine of preventing and treating diabetes or health product.
The specific embodiment:
Embodiments of the invention 1: get fly maggot chitosan 1000g, become 100～200 fine particle with the micropowder apparatus processing, add emulsifier for mixing and become suspension, send in the colloid mill and filter, the mud shape gel that obtains is sent into pill in the pellet processing machine, gets soft gelatin capsule; Get soft capsule with carrying out ungrease treatment after the soft gelatin capsule typing, send into again in the drying machine and get the finished product soft capsule through redrying.Said preparation is oral, and 4g/ time, 2 times/day, have the effect of blood sugar regulation, can be used for treating diabetes.
Embodiments of the invention 2: get fly maggot chitosan 1000g, Fructus Momordicae charantiae 150g and Radix Puerariae 200g, pulverize, sieve, add appropriate amount of auxiliary materials, mixing, oven dry, sterilization, packing is made granule or capsule.Said preparation is oral, and 6g/ time, 2 times/day; Have two-way immunoloregulation function, blood sugar lowering and blood fat reducing, reinforcement liver function and antifatigue effect are arranged.
Embodiments of the invention 3: get fly maggot chitosan 1000g, be dissolved in pH and be 3.5 hydrochloric acid or aqueous acetic acid, form gel, make slow release, controlled release form according to a conventional method.Said preparation is oral, and 2g/ time, 2 times/day, be used for the generation of prevent diabetes, diabetes Susceptible population there is positive preventive and therapeutic effect.
Embodiments of the invention 4: get fly maggot chitosan 1000g and spirulina polysaccharide 200g, mixing is standby behind drying, porphyrize, mistake 100 mesh sieves respectively; Progressively increase method with aforementioned mixture and dextrin mixing with equivalent, add the abundant mixing of starch and microcrystalline Cellulose again, stir the alcoholic solution system soft material that spraying down adds 30% mass percent, granulate, cross 16 mesh sieves, 60 ℃ are dried to moisture and are about 5%, sieve, granulate, add Pulvis Talci, mix homogeneously, tabletting is made tablet.Said preparation is oral, 6 slices/time, 2 times/day, is used for the control of diabetes.
Claims (10)
1. the application of fly maggot chitosan in the product of preparation blood sugar regulation, described fly maggot chitosan is to be raw material with the fly larvae chitin, adopts the soda acid chemical method to carry out deacetylation and makes.
2. the application of the described fly maggot chitosan of claim 1 in the product of preparation prevention or treatment diabetes.
3. according to the application of claim 1 or 2 described fly maggot chitosans, it is characterized in that: described product is medicine or health product.
4. according to the application of the described fly maggot chitosan of claim 3, it is characterized in that: fly maggot chitosan and pharmaceutical carrier or excipient are prepared into pharmaceutical preparation according to conventional method.
5. according to the application of the described fly maggot chitosan of claim 4, it is characterized in that: get fly maggot chitosan, become 100～200 fine particle with the micropowder apparatus processing, add emulsifier for mixing and become suspension, send in the colloid mill and filter, the mud shape gel that obtains is sent into pill in the pellet processing machine, gets soft gelatin capsule; Get soft capsule with carrying out ungrease treatment after the soft gelatin capsule typing, send into again in the drying machine and get the finished product soft capsule through redrying.
6. according to the application of the described fly maggot chitosan of claim 3, it is characterized in that: with fly maggot chitosan and the combination of other medicinal ingredient, add pharmaceutical carrier or excipient, be prepared into pharmaceutical preparation according to conventional method.
7. according to the application of the described fly maggot chitosan of claim 6, it is characterized in that: get fly maggot chitosan 1000g, Fructus Momordicae charantiae 150g and Radix Puerariae 200g, pulverize, sieve, add appropriate amount of auxiliary materials, mixing, oven dry, sterilization, packing is made granule or capsule.
8. according to the application of the described fly maggot chitosan of claim 3, it is characterized in that: with fly maggot chitosan separately or with other combinations of substances, be prepared into health product according to conventional method.
9. according to the application of the described fly maggot chitosan of claim 8, it is characterized in that: get fly maggot chitosan, be dissolved in pH and be 3.5 hydrochloric acid or aqueous acetic acid, form gel, make slow release, controlled release preparation according to a conventional method.
10. according to the application of the described fly maggot chitosan of claim 8, it is characterized in that: get fly maggot chitosan 1000g and spirulina polysaccharide 200g, mixing is standby behind drying, porphyrize, mistake 100 mesh sieves respectively; Progressively increase method with aforementioned mixture and dextrin mixing with equivalent, add the abundant mixing of starch and microcrystalline Cellulose again, stir the alcoholic solution system soft material that spraying down adds 30% mass percent, granulate, cross 16 mesh sieves, 60 ℃ are dried to moisture is 5%, sieve, granulate, add Pulvis Talci, mix homogeneously, tabletting is made tablet.
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| CN2007102010366A CN101103995B (en) | 2007-07-10 | 2007-07-10 | Application of fly maggot chitosan in preparing product regulating blood sugar |
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| CN101103995B true CN101103995B (en) | 2011-06-01 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103251100B (en) * | 2013-06-03 | 2014-12-03 | 陈道才 | Maggot peptide beverage and production technology thereof |
| CN105496982B (en) * | 2015-12-24 | 2018-10-19 | 广东药科大学 | A kind of chitosan tablet and preparation method thereof |
| CN108125978A (en) * | 2017-12-29 | 2018-06-08 | 广州润虹医药科技股份有限公司 | A kind of chitin fiber composition and preparation method thereof |
| CN110302213A (en) * | 2019-07-16 | 2019-10-08 | 华祥荣 | Maggot is for treating the application in diabetes |
| CN113248313B (en) * | 2021-06-02 | 2023-04-14 | 中诚国联（河南）生物科技有限公司 | Composite microbial fertilizer and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1340461A (en) * | 2000-08-28 | 2002-03-20 | 李高霖 | Drinking water containing chitosan |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1340461A (en) * | 2000-08-28 | 2002-03-20 | 李高霖 | Drinking water containing chitosan |
Non-Patent Citations (2)
| Title |
|---|
| 张鹭.昆虫表皮蛋白的研究进展及其应用前景.《广东蚕业》.2006,第40卷(第3期),第38至42页. * |
| 王雷等.蝇类的开发与利用1).《东北林业大学学报》.2004,第32卷(第6期),第97至98页. * |
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