CN107827997A - A kind of hydrophobization glucan and its preparation method and application - Google Patents
A kind of hydrophobization glucan and its preparation method and application Download PDFInfo
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- CN107827997A CN107827997A CN201711009095.3A CN201711009095A CN107827997A CN 107827997 A CN107827997 A CN 107827997A CN 201711009095 A CN201711009095 A CN 201711009095A CN 107827997 A CN107827997 A CN 107827997A
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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Abstract
The present invention relates to technical field of organic synthesis, a kind of more particularly to hydrophobization glucan and its preparation method and application, the hydrophobization glucan is that the hydroxyl of glucan is reacted with succinic anhydride, first prepare the glucan butyrate with butyric acid group, reacted again with cyclohexyl urea, so that carboxyl is modified by cyclohexyl urea, hydrophobization glucan is obtained.The hydrophobization glucan has self-emulsifying, suitably as protein medicaments, amino acids drug, vaccine type medication, agricultural chemicals, anti-inflammatory, antimicrobial carrier, can also independent medication.
Description
Technical field
The present invention relates to technical field of organic synthesis, more particularly to a kind of hydrophobization glucan and preparation method thereof and should
With.
Background technology
Medicine-carried nano particles refer generally to particle diameter below 500 nanometers, using with hydrophily and hydrophobic polymer material as
Carrier, medicine are wrapped in core, and hydrophilic segment is distributed in the particulate of shell formation.Hydrophobic polysaccharide synthesized by the present invention,
Not only there is hydrophobic end group, also with urea groups and ester group, hydrophobic sample effect, also hydrogen bond are not only produced with the medicine loaded
Key and effect, therefore, it is very easy to load amino acid, peptides and protein medicaments.Other kinds of medicine can also be loaded simultaneously
Thing.This carrier also has affinity interaction, independent medication, can play antibacterial action for being made up of the bacterium class of cell membrane peptide glycan.
The content of the invention
First purpose of the present invention is to provide a kind of hydrophobization glucan, hereinafter referred to as hydrophobic polysaccharide.It is described hydrophobic
It is using succinic acid as linking arm to polysaccharide to change polysaccharide and be, succinic acid that end group is modified with cyclohexyl urea is with ester bond and glucan
Hydroxyl is connected.The molecular weight of the hydrophobic polysaccharide is not particularly limited.
The hydrophobic polysaccharide, there is self-emulsifying, can be used as emulsifying agent carry medicine, can also independent medication.
Second object of the present invention is to provide the preparation method of above-mentioned hydrophobic polysaccharide, the step of the preparation method and
The reaction mechanism mechanism of reaction is：
(1) glucan succinate is prepared：Glucan and succinic anhydride are reacted using pyridine as catalyst in the solution
To butyric acid glucan；
(2) hydrophobic polysaccharide is prepared：In a solvent, the butyric acid glucan is 20 according to weight ratio with cyclohexyl urea：
(1-10) reacts, and obtains the hydrophobic polysaccharide.
Preferably, the concrete operations of step (2) are：It is 20 according to the weight ratio of polysaccharide and cyclohexyl urea：(1-10) is counted, will
The polysaccharide is dissolved in solvent, and cyclohexyl urea is added into the solvent, is reacted under the conditions of 10-80 DEG C, and reaction is completely backward
Water is added in reaction solution, alcohols solvent is added into the filtrate and separates out solid, the solid is hydrophobization heparin.
Wherein, the solvent is dimethylformamide, dimethyl sulfoxide (DMSO) or dichloromethane.
The alcohols solvent is ethanol.
Third object of the present invention is to provide application of the above-mentioned hydrophobic polysaccharide as pharmaceutical carrier in medicine preparation.
Preferably, the hydrophobic polysaccharide be applied to separately as albumen, polypeptide, amino acids, anti-microbial type, pesticide,
The carrier of anti-inflammatory class, camptothecin analogues class medicine.
The hydrophobic polysaccharide is also suitable for the carrier separately as vaccine type medication.The antigenic source of the vaccine is in thin
The infection of bacterium, virus, fungi and protozoon to animal, such as microorganism Inf luenzaA types, InfluenzaB types, hepatitis C
Virus, hepatitis A virus, hepatitis B virus, Rotavirus viruses, Cytomegalovirus：CMV viruses, RS viruses, pharynx
The viral type of 1 type 2 of head conjunctiva heat, HIV, varicellazoster virus, simple herpes, ATL (adult T cell leukemia)
Virus, Coxsackie viruses, entero are viral, sudden dermexanthesis viral (HHV-6), measles virus, rubella virus, popularity
Parotid gland inflammation is viral, the scorching virus of acute grey white pulp, japanese encephalitis virus, hydrophobin, hepatitis C virus, N orwalk are sick
Poison, hydrophobin, RS viruses, Cytomegalovirus viruses, foot and mouth disease virus, infectious gastroenteritis virus, rubella
Poison, ATL viruses, adeno viruses, Echov irus, Herpes be viral, natural poxvirus, dengue fever fever viruses, yellow heat
Virus, West Nile virus, SARS (virus), Ebola hemorrhagic fever virus, Marburg hemorr hagic fever,
Pathogenic virus such as Lassa fever viruses, Hantavirus, Nipah virus infection etc.；The bacterium goes out for intestinal tube
The pathogenicity such as courageous and upright coliform coliform, staphylococcus aureus, meningitis bacterium, Pseudomonas aeruginosa, the chain coccus of worm tooth, Cholera
Bacterium, Typhus bacterium, Chlamydophila felis dysentery characterized by blood in the stool bacterium, pneumococcus, bacillus pertussis, Corynebacter ium
Diphtheriae bacterium, tetanolysin, Influenza bacterium, pestis bacterium, botulinum bacterium, Bacillus anthracis charcoals
Ancient sacrificial utensil bacterium, hare germ, Salmonella bacterium, VRE (enterococcus), tulase, dysentery characterized by blood in the stool bacterium, Salmonella Typhi intestines bacterium,
Salmonella Paratyphi A bacterium, Chlamydophila felis bacterium, Ameba dysentery characterized by blood in the stool, Legionella bacterium, Lyme
The pathogenic bacterias such as sick (undulant fever) bacterium of borreliosis bacterium, brucellosis；Coxiella burnetiiQ heat,
The Rickettsia such as Chlamydia；The protozoon classes such as malaria protozoon, Cryptosporidium Tyzzer；
The proteantigen of the microorganisms such as the fungies such as cryptococcosisaspergillosis.Pathogenic microorganism proteantigen
Including amino acid, enzyme, hormone and immune regulator, the molecular weight of these materials does not limit.
Fourth object of the present invention is to provide more than one and states any hydrophobic polysaccharide as carrier preparation load powder
Method：Amino acid carries out emulsification treatment with the hydrophobic polysaccharide and produces load powder in aqueous.
Preferably, the weight ratio of amino acid and the hydrophobic polysaccharide is 10:1-10:100, preferably 10:3-10:50.
The present invention is provided a kind of preferably prepared using any of the above-described hydrophobic polysaccharide as carrier and carries the sub method of powder：According to
The weight of amino acid and hydrophobic polysaccharide ratio is 10:3-10:10 meters, it is first that amino acid is soluble in water, it is more then to add hydrophobization
Sugar, using mulser emulsification treatment until formation nano-particle, obtains mixed solution, produce the load powder under the conditions of 1-50 DEG C
Below 400 nanometers, there is a small amount of micron-sized condensate in son, particle footpath mostly.And hydrophobization glucan aqueous solution there are no it is micro-
Meter level particle.
Embodiment
Following examples are used to illustrate the present invention, but are not limited to the scope of the present invention.
The preparation method of the polysaccharide of embodiment 1
A kind of preparation method of polysaccharide, the preparation method are specially：Glucan 20g is dissolved in 200ml dimethyl Asia
Sulfone, butanoic anhydride 10g, pyridine 2ml is added to add deionized water stopped reaction in room temperature reaction 4h.Add 2.54L ethanol.Static 3h, it is heavy to separate out
Form sediment, refined again with ethanol, be dried under reduced pressure to obtain butyric acid polysaccharide.
The method that embodiment 2 prepares hydrophobic polysaccharide using polysaccharide as raw material
The butyric acid polysaccharide 200mg that embodiment 1 is prepared is dissolved in dimethyl sulfoxide (DMSO), adds cyclohexyl urea 50mg,
1h is reacted under the conditions of 10 DEG C, after reaction completely, the 20ml aqueous solution is added into reaction solution, is carried out using 1000ml deionized waters saturating
The removal of impurity is gone in analysis, obtains dialyzate, 500ml ethanol is then added into the dialyzate, the material of precipitation is the hydrophobization
Polysaccharide.
Embodiment 3 carries the preparation of powder
The present embodiment is provided using the hydrophobic polysaccharide that embodiment 2 is prepared as carrier, prepares the method for carrying powder, institute
The method of stating is：
It is soluble in water by hydrophobic polysaccharide 10mg, add 5mg glycine, emulsify the nano-particle for producing and loading amino acid.
This hydrophobic polysaccharide medicine-carried nano particles are in polydispersion state.Fig. 1, Fig. 2 are hydrophobization glucan glycine carrier
The particle footpath and its distribution that medicine and hydrophobic polysaccharide particles distribution instrument are surveyed.
Brief description of the drawings
Fig. 1 is that hydrophobization glucan loads the particle footpath formed in aqueous after glycine and its distribution.Detecting instrument
For Zetasizer Nano Particle Size Analyzers.Fig. 2 is hydrophobization glucan aqueous solution particle footpath and its distribution.Hydrophobization glucan
Below 400 nanometers, there is a small amount of micron-sized condensate in the particle footpath formed in aqueous after loading glycine mostly.And dredge
The hydroglucan aqueous solution there are no micro-size particles.
Although above the present invention is made to retouch in detail with general explanation, embodiment and experiment
State, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, are belonged to claimed
Scope.
Claims (10)
1. a kind of hydrophobization glucan, the hydrophobization glucan is as linking arm and to terminal carboxyl group cyclohexyl using succinic acid
Urea is modified.
2. hydrophobization glucan according to claim 1, it is characterised in that：The molecular weight of the hydrophobization glucan is without spy
It is different to limit.
3. prepare the method for the hydrophobization glucan described in claim 1 or 2, it is characterised in that methods described includes following step
Suddenly：
(1) butyric acid esterification glucan is prepared：Glucan is first reacted with succinic anhydride in a solvent, obtains butyric acid esterificated polysaccharide,
It can also be the reaction carried out with other dicarboxylic anhydrides；
(2) hydrophobization glucan is prepared：In a solvent, the polysaccharide is 20 according to weight ratio with cyclohexyl urea: (1-10) occurs
Reaction, obtains the hydrophobization glucan.
4. preparation method according to claim 3, it is characterised in that：Before hydrophobization glucan is prepared, first by described in
Glucan is pre-processed, and the pretreatment is：Glucan is soluble in water, ion exchange column is crossed, using deionized water as elution
Liquid, eluent is collected, and alkali is added into salt into the eluent, be dried under reduced pressure and produce after freezing；Preferably, the alkali is three
Butylamine.
5. the method according to claim 3 or 4, it is characterised in that：The concrete operations of step (2) are：By the glucan
It is dissolved in solvent, cyclohexyl urea is added into the solvent, is reacted under the conditions of 10-80 DEG C, reacts in completely backward reaction solution
Water is added, alcohols solvent is added into the solvent and separates out solid, the solid is hydrophobization glucan；Preferably, it is described
Solvent is dimethylformamide, dimethyl sulfoxide (DMSO) or dichloromethane；Preferably, the alcohols solvent is ethanol.
6. any described preparation method of hydrophobization glucan or claim 3-5 described in claim 1 or 2 obtains hydrophobic
Change application of the glucan as medicine or pharmaceutical carrier in medicine preparation, it is characterised in that：The medicine be amino acids,
Camptothecin analogues class, peptides, vaccine, protide, antimicrobial class, anti-inflammatory agent class, pesticide.
7. a kind of hydrophobization glucan with described in claim 1 or 2, or any described hydrophobization Portugals of claim 3-5 gather
Sugar prepares the method for carrying powder for carrier, it is characterised in that：Methods described is：Amino acid is with hydrophobization glucan in the aqueous solution
Middle emulsification, obtains medicament-carried nano emulsion, and the amino acid comes from common drug.
8. according to the method for claim 7, it is characterised in that：The weight ratio of the medicine and the hydrophobization glucan is
10: 1-10: 100, preferably 10: 4-10: 50.
9. the method according to claim 7 or 8, it is characterised in that：Methods described is：Gather according to amino acid and hydrophobization Portugal
The weight ratio of sugar is 1: 1-1: 10 meters, and first amino acid is dissolved in the aqueous solution, then adds hydrophobization glucan, at 2-30 DEG C
Under the conditions of using probe emulsifier processing until formed nano-particle, obtain mixed solution, can also add corresponding antioxidant,
Preservative, antifreezing agent etc..The various formulations such as injection, powder-injection, suppository can be made.
10. according to any described methods of claim 7-9, it is characterised in that：Described hydrophobization glucan can also be with low
Anticoagulant property heparin, starch, amylopectin, amylose, pulullan polysaccharide, ethoxy dextran, mannosan, fruit gather
Sugar, synanthrin, chitin, chitosan, chitin, xyloglucan and water-soluble cellulose etc. are prepared by raw material.
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| CN201711009095.3A CN107827997A (en) | 2017-10-25 | 2017-10-25 | A kind of hydrophobization glucan and its preparation method and application |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110156911A (en) * | 2019-05-20 | 2019-08-23 | 蚌埠医学院 | Hydrophobic polysaccharide and its preparation method and application |
| CN113563493A (en) * | 2021-07-01 | 2021-10-29 | 蚌埠医学院 | Hydrophobic polysaccharide and preparation method and application thereof |
| CN113603806A (en) * | 2021-07-16 | 2021-11-05 | 武汉纳乐吉生命科技有限公司 | Cysteamine derivative based on dextran modification, preparation and application thereof |
| CN116589606A (en) * | 2022-12-01 | 2023-08-15 | 中国药科大学 | Butyrylated yeast glucan as well as preparation method and application thereof |
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| CN102516416A (en) * | 2011-12-28 | 2012-06-27 | 蚌埠医学院 | Method for synthesizing heparin ester |
| CN103483469A (en) * | 2013-09-26 | 2014-01-01 | 上海大学 | Preparation method for water-soluble chitosan |
| CN105418804A (en) * | 2015-12-01 | 2016-03-23 | 蚌埠医学院 | Hydrophobic low-anticoagulation heparin as well as preparation method and application thereof |
| CN106986951A (en) * | 2016-01-21 | 2017-07-28 | 蚌埠医学院 | A kind of hydrophobic polysaccharide and its preparation method and application |
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2017
- 2017-10-25 CN CN201711009095.3A patent/CN107827997A/en active Pending
Patent Citations (4)
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| CN102516416A (en) * | 2011-12-28 | 2012-06-27 | 蚌埠医学院 | Method for synthesizing heparin ester |
| CN103483469A (en) * | 2013-09-26 | 2014-01-01 | 上海大学 | Preparation method for water-soluble chitosan |
| CN105418804A (en) * | 2015-12-01 | 2016-03-23 | 蚌埠医学院 | Hydrophobic low-anticoagulation heparin as well as preparation method and application thereof |
| CN106986951A (en) * | 2016-01-21 | 2017-07-28 | 蚌埠医学院 | A kind of hydrophobic polysaccharide and its preparation method and application |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110156911A (en) * | 2019-05-20 | 2019-08-23 | 蚌埠医学院 | Hydrophobic polysaccharide and its preparation method and application |
| CN113563493A (en) * | 2021-07-01 | 2021-10-29 | 蚌埠医学院 | Hydrophobic polysaccharide and preparation method and application thereof |
| CN113563493B (en) * | 2021-07-01 | 2022-06-24 | 蚌埠医学院 | Hydrophobic polysaccharide and preparation method and application thereof |
| CN113603806A (en) * | 2021-07-16 | 2021-11-05 | 武汉纳乐吉生命科技有限公司 | Cysteamine derivative based on dextran modification, preparation and application thereof |
| CN116589606A (en) * | 2022-12-01 | 2023-08-15 | 中国药科大学 | Butyrylated yeast glucan as well as preparation method and application thereof |
| CN116589606B (en) * | 2022-12-01 | 2024-05-28 | 中国药科大学 | Butyrylated yeast glucan as well as preparation method and application thereof |
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