CN106109400A - A kind of oral drugs hydrogel slow-released carrier and preparation method and applications - Google Patents
A kind of oral drugs hydrogel slow-released carrier and preparation method and applications Download PDFInfo
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- CN106109400A CN106109400A CN201610587453.8A CN201610587453A CN106109400A CN 106109400 A CN106109400 A CN 106109400A CN 201610587453 A CN201610587453 A CN 201610587453A CN 106109400 A CN106109400 A CN 106109400A
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- hydrogel
- chitosan
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- oral drugs
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Classifications
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- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
-
- 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
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
Abstract
The invention discloses a kind of oral drugs hydrogel slow-released carrier and preparation method and applications, belong to technical field of medicine.With chitosan, dialdehyde starch, gelatin, polyvinyl alcohol as raw material, it is mixed in proportion into uniform solution, is administered orally to stomach, can quickly form gel, contained medicine is played parcel, slow releasing function, reduce the injury that receptor is caused by high drug level.Medicine can slowly be discharged at stomach, is particularly well-suited to treat disease of stomach.
Description
Technical field
The invention belongs to technical field of medicine, relate to a kind of oral drugs hydrogel slow-released carrier and preparation method
And application.
Background technology
Common administering mode, medicine prolonged high concentrations in vivo discharges, holds time short, and undulatory property is relatively big, easily causes
Receptor sensitivity reduces, and does not only reach due curative effect, it is also possible to produce drug resistance, even side effect.Medicine controls slow
System of releasing makees carrier with certain material, and medicine is made certain dosage form, and slow releasing carrier of medication can control medicine releasing in vivo
Put, make medicine according to the dosage set, the most slowly discharge with certain speed in reasonable time, extend medicine effect
Time, reduce drug degradation and loss, reduce drug side effect, improve utilization ratio of drug, produce stable blood drug level, reduce
Administration number of times, thus more effectively treat certain disease.Therefore, the pharmaceutical carrier that preparation can make the medicine of carrying slowly discharge is
Very important.
There is the hydrogel of three-dimensional crosslinked network, do not dissolve, certain shape can be kept, but permissible
Swelling water suction, has temperature and the pH respondent behavior of uniqueness, and the aqueous environments of hydrogel is suitable for the expansion of polar medicine molecule
Dissipate, thus can be used as medicine and control slow-releasing system.CN103467755A discloses " a kind of medicament slow release hydrogel and preparation side thereof
Method and purposes ", use high-voltage electrostatic liquid droplet to prepare the calcium alginate microsphere of single dispersing drug containing, then by the calcium alginate of medicine carrying
Microsphere is placed in hydrogel network structure, thus realizes medicament slow release, has good elasticity, water-absorbing-retaining, air-and water-permeable etc.
Performance；But calcium alginate is not readily dissolved in water, its preparation process is loaded down with trivial details.CN101214217A disclose " hydrogel-hydrogel be combined
Material and preparation method thereof and use of medicament sustained-release matrix ", although it carries, easy to use, stores the time long, but its application model
Enclose little, be only applicable to corneal contact lens slow release medicament for the eyes；And easy residual initiator and cross-linking agent etc. in carrier, biocompatibility is relatively
Difference.Zhang Yinye etc. are at " sodium alginate/sulfation fructose-chitosan the compound water congealing of a kind of novel protein class drug oral carrier
Glue " in be prepared for injectable sodium alginate/sulfation fructose-chitosan composite aquogel, when pH value is 6.8 and 7.4, cattle
The release rate of serum albumin (BSA) increases, can be as a kind of oral protein medicament carrier, but chitosan is converted into sulfation
The process of fructose-chitosan is more complicated.Summary is described, although hydrogel can be as good pharmaceutical carrier, pharmaceutical hydrogel
Carrier is further improved, and needs to invent the pharmaceutical carrier being more suitable for.
Summary of the invention
It is to provide one of goal of the invention to be for existing pharmaceutical hydrogel slow release for solving above-mentioned technical problem purpose
The not enough of carrier provides a kind of oral drugs hydrogel slow-released carrier and preparation method and applications.
The technical scheme proposed to solve one of them technical problem above-mentioned is: a kind of oral drugs hydrogel slow release
Carrier, it is characterised in that: it is that raw material is prepared from by chitosan, dialdehyde starch, gelatin, polyvinyl alcohol, the volume proportion of raw material
For chitosan 30%～50%, dialdehyde starch 5%～20%, gelatin 10%～40%, polyvinyl alcohol 5%～15%.
Preferably, the deacetylation of described chitosan is more than 85%.
Preferably, described dialdehyde starch, gelatin, the purity of polyvinyl alcohol all reach medicinal standard.
The technical scheme proposed to solve one of them technical problem above-mentioned is: a kind of oral drugs hydrogel slow release
The preparation method of carrier, comprises the steps:
(1) preparation solution: preparation mass fraction is 2.0～the chitosan of 8.0%, dialdehyde starch, gelatin, polyethylene respectively
The aqueous solution of alcohol；
(2) mixed solution: mixed with dialdehyde starch solution by chitosan solution, forms chitosan/dialdehyde starch mixing molten
Liquid, adds gelatin solution body, is eventually adding poly-vinyl alcohol solution；
(3) crosslinking: the mixed solution mix homogeneously being made up of chitosan, dialdehyde starch, gelatin and polyvinyl alcohol, is placed in
In acid solution, will crosslink rapidly, take out after forming the hydrogel of stable and uniform；
(4) washing: with milli-Q water hydrogel to neutral, i.e. obtain hydrogel finished product.
Preferably, acid solution pH is not higher than 4.
The technical scheme proposed to solve one of them technical problem above-mentioned is: a kind of oral drugs hydrogel slow release
The application of carrier, the application in oral drugs carrier medicament of the described oral drugs hydrogel slow-released carrier.
Preferably, described oral drugs hydrogel slow-released carrier application in preparation treatment disease of stomach medicine.
Beneficial effect:
1. the hydrogel of the present invention is with chitosan, dialdehyde starch as primary raw material, and wherein chitosan is the derivative of chitin
Thing, chitosan natural production is high, nontoxic, non-stimulated, without immunogen, without heat source response, not haemolysis, without mutagenicity, also can from
So degrade, there is the features such as outstanding histocompatibility；Dialdehyde starch forms through starch conversion, is a kind of renewable, degradable
Material, there is the character such as certain viscosity, film forming, gelation and bonding.Additionally, with water as solvent, chitosan forms sediment with dialdehyde
Powder can crosslink under acid condition is catalyzed, and forms gel, i.e. chitosan and can be formed solidifying under gastric juice environment with dialdehyde starch
Glue, forming process is harmless, has typical pH value response characteristic, and whole preparation process is simple.Therefore, acidic gastric juice environment is shell
Polysaccharide and the native catalytic environment of dialdehyde starch crosslinked formation gel, it is adaptable to the carrier of oral drugs.Gelatin, polyvinyl alcohol are then
Can optimize the performance of hydrogel further, pharmaceutical pack is wrapped in hydrogel network, makes moisture can not quickly enter internal dissolving
Medicine, medicine discharges with the slowly degraded of hydrogel, is a kind of novel hydrogel drug carrier.
2. raw material easily obtains: chitosan used is the derivant of chitin, aboundresources；Dialdehyde starch, gelatin are all sky
So macromolecular material, the most extensively obtains.Advantages of nontoxic raw materials, non-stimulated, without immunogen, and there is biocompatibility and the degraded of excellence
Performance.
3. with water as solvent, being mixed in proportion by raw material, under sour environment, catalytic crosslinking becomes gel, the letter of whole preparation process
Single.
4. sour environment is the catalyst environment forming hydrogel, and hydrogel is applicable to the carrier of oral drugs, the suitableeest
For treating disease of stomach.
5. deacetylating degree of chitosan is more than 85%, and the dissolubility of chitosan is high, is beneficial to crosslinking the most below.Described dialdehyde forms sediment
Powder, gelatin, the purity of polyvinyl alcohol all reach medicinal standard, it is ensured that purity is high.
Accompanying drawing explanation
Fig. 1 is embodiment 1 chitosan, dialdehyde starch, the infrared spectrum of composite aquogel.
Fig. 2 is the scanning electron microscope (SEM) photograph of hydrogel section after embodiment 2 lyophilization.
Fig. 3 is the scanning electron microscope (SEM) photograph of hydrogel surface after embodiment 3 lyophilization.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but embodiment is not limited to secondary,
The material of all technology realized based on foregoing of the present invention and preparation belongs to protection scope of the present invention.
Embodiment 1
The deacetylation of described chitosan is more than 85%, and described dialdehyde starch, gelatin, the purity of polyvinyl alcohol all reach medicine
Use standard.2g chitosan, 2g dialdehyde starch, 2g gelatin, 2g polyvinyl alcohol are dissolved in 50g deionized water, respectively by prepare
Chitosan solution, dialdehyde starch solution, gelatin solution, poly-vinyl alcohol solution press the volume ratio mix homogeneously of 5:0.8:3:0.5.Will
The solution prepared inserts catalytic crosslinking in the acidic aqueous solution that pH is 3.0, obtains hydrogel, use deionized water after standing 5 minutes
Soaking for several times to neutral, obtain hydrogel finished product, after lyophilization, dried hydrogel is carried out ultrared spectrum analysis, and (result is the most attached
Fig. 1).It can be seen that 1450～1670cm-1Vibration peak confirm Schiff (i.e. imine linkage) exist, it was demonstrated that water
Gel is formed stable imine linkage.
Embodiment 2
2g chitosan, 2g dialdehyde starch, 2g gelatin, 2g polyvinyl alcohol are dissolved in 50g deionized water, respectively by prepare
Chitosan solution, dialdehyde starch solution, gelatin solution, poly-vinyl alcohol solution press the volume ratio mix homogeneously of 5:1.2:3.5:0.6.
The solution prepared is added in the acid solution that pH is 4.0 and is catalyzed, obtain hydrogel after standing 5 minutes, soak with deionized water
To neutral, obtain hydrogel finished product, after lyophilization, brittle failure after liquid nitrogen cooling, expose section, hydrogel section is scanned
Electron-microscopic analysis (result such as accompanying drawing 2).As can be seen from the figure hydrogel section becomes multiple structure, there is a large amount of cavity,
Confirm that hydrogel has the water absorption and swelling performance of excellence.
Embodiment 3
2g chitosan, 2g dialdehyde starch, 2g gelatin, 2g polyvinyl alcohol are dissolved in 50g deionized water, respectively by prepare
Chitosan solution, dialdehyde starch solution, gelatin solution, poly-vinyl alcohol solution are uniformly mixed by the volume ratio of 5:1.6:4:0.7.Will
The solution prepared adds catalysis in the acid solution that pH is 3, obtains hydrogel, in being dipped to deionized water after standing 5 minutes
Property, obtain hydrogel finished product.Lyophilization, carries out electron-microscope scanning (result such as accompanying drawing 3) to hydrogel surface.Can from figure
Going out, the microcosmic surface of hydrogel surface is smooth, and breaking part is the most regular.
Accordingly, on the premise of without departing from the present invention above-mentioned basic fundamental thinking, universal according to this area
Knowledge and technology means, add the other biological compatibility and medicine component in hydrogel, broadly fall into present invention
The amendment of various ways, replace and change, belong to the scope of the present invention.
Claims (7)
1. an oral drugs hydrogel slow-released carrier, it is characterised in that: by chitosan, dialdehyde starch, gelatin, polyvinyl alcohol
Be prepared from for raw material, the volume proportion of raw material be chitosan 30%～50%, dialdehyde starch 5%～20%, gelatin 10%～
40%, polyvinyl alcohol 5%～15%.
Oral drugs hydrogel slow-released carrier the most according to claim 1, it is characterised in that: the de-second of described chitosan
Acyl degree is more than 85%.
Oral drugs hydrogel slow-released carrier the most according to claim 1, it is characterised in that: described dialdehyde starch, bright
Glue, the purity of polyvinyl alcohol all reach medicinal standard.
4. according to a preparation method for the arbitrary described oral drugs hydrogel slow-released carrier of claims 1 to 3, its feature
It is to comprise the steps:
(1) preparation solution: preparation mass fraction is 2.0～the chitosan of 8.0%, dialdehyde starch, gelatin, polyvinyl alcohol respectively
Aqueous solution；
(2) mixed solution: mixed with dialdehyde starch solution by chitosan solution, forms chitosan/dialdehyde starch mixed solution, then
Add gelatin solution body, be eventually adding poly-vinyl alcohol solution；
(3) crosslinking: the mixed solution mix homogeneously being made up of chitosan, dialdehyde starch, gelatin and polyvinyl alcohol, is placed in acidity
In solution, will crosslink rapidly, take out after forming the hydrogel of stable and uniform；
(4) washing: with milli-Q water hydrogel to neutral, i.e. obtain hydrogel finished product.
The preparation method of oral drugs hydrogel slow-released carrier the most according to claim 4, it is characterised in that: acid molten
Liquid pH is not higher than 4.
6. according to the application of hydrogel slow-released carrier of the oral drugs described in claim 1-3, it is characterised in that: described oral
Medicine hydrogel slow-released carrier application in oral drugs carrier medicament.
7. according to the application of hydrogel slow-released carrier of the oral drugs described in claim 1-3, it is characterised in that: described oral
Medicine hydrogel slow-released carrier is preparing the application treated in disease of stomach medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610587453.8A CN106109400A (en) | 2016-07-22 | 2016-07-22 | A kind of oral drugs hydrogel slow-released carrier and preparation method and applications |
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| CN201610587453.8A CN106109400A (en) | 2016-07-22 | 2016-07-22 | A kind of oral drugs hydrogel slow-released carrier and preparation method and applications |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021007899A1 (en) * | 2019-07-15 | 2021-01-21 | 浙江工业大学 | Injectable hydrogel material and preparation method therefor and use thereof |
| CN114009797A (en) * | 2021-11-17 | 2022-02-08 | 上海市第十人民医院 | Weight-losing composition and preparation method and application thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021007899A1 (en) * | 2019-07-15 | 2021-01-21 | 浙江工业大学 | Injectable hydrogel material and preparation method therefor and use thereof |
| CN114009797A (en) * | 2021-11-17 | 2022-02-08 | 上海市第十人民医院 | Weight-losing composition and preparation method and application thereof |
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