CN110384655A - A kind of preparation method of high-biocompatibility pharmaceutical carrier hydrogel - Google Patents
A kind of preparation method of high-biocompatibility pharmaceutical carrier hydrogel Download PDFInfo
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- CN110384655A CN110384655A CN201910813481.0A CN201910813481A CN110384655A CN 110384655 A CN110384655 A CN 110384655A CN 201910813481 A CN201910813481 A CN 201910813481A CN 110384655 A CN110384655 A CN 110384655A
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- hydrogel
- sodium alginate
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- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
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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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- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
The invention discloses a kind of preparation methods of high-biocompatibility pharmaceutical carrier hydrogel.The present invention chooses sodium alginate, chitosan as raw material, prepares high intensity hydrogel using the electrostatic interaction between two kinds of oppositely charged polyelectrolyte；The addition of carboxymethyl nano-cellulose improves the pH sensibility and mechanical property of hydrogel entirety simultaneously；Furthermore the hydrogel after oxidation is conducive to improve the degeneration energy of hydrogel；Finally, the composite hydrogel has certain Indomethacin slow release effect.The raw materials used in the present invention is sodium alginate, chitosan, carboxymethyl nano-cellulose, has preferable environment friendly, biocompatibility；Reaction condition of the present invention is mild, does not need the chemical substances such as crosslinking agent, photoinitiator, provides new approaches for Indomethacin medicament slow release.
Description
Technical field
The present invention relates to biomedical material technologies, and in particular to a kind of high-biocompatibility pharmaceutical carrier hydrogel
Preparation method.
Background technique
Hydrogel is a kind of hydrophilic polymer, can be by chemically or physically forming cross-linked network structure, and hydrogel is insoluble
Yu Shui, can water absorption and swelling, the hydrogel after swelling can keep original solid shape.Hydrogel is soft, and water content is high, and has
The characteristics such as good biocompatibility and biodegradable are a kind of biomaterials with excellent performance, are led in bioengineering
Domain, field of drug delivery play an important role.Hydrogel can load certain drug and be fixed in privileged site, be used for
Local treatment can also extend the release time of drug, reduce side effects of pharmaceutical drugs.The common hydrogel raw material for preparing has: melon
Your glue, chitosan, cellulose, sodium alginate, starch etc..
Hydrogel can be divided into chemical crosslinking and physical crosslinking according to the crosslinking method for constituting hydrogel three-dimensional network,
Middle physical crosslinking includes that hydrogen bond, electrostatic interaction, hydrophobic effect etc. do not have compared with the hydrogel of Chemical Crosslinking Methods preparation
There are chemical cross-linking agent, photoinitiator etc. that may generate the chemical substance of toxicity, therefore the three of Physical cross linking methods building to cell
It is relatively preferable to tie up network biocompatibility.Utilize the chelation structure between the carboxylate radical and calcium ion on sodium alginate strand
Sodium alginate-calcium ion crosslinking hydrogel is built since its gelation speed is fast, lubricity is good and biocompatibility is preferable, it is extensive
For the research of repair of cartilage hydrogel, but the hydrogel of this method preparation due to calcium ion be easy in vivo by it is other from
Son replaces, and can not be stabilized in vivo so as to cause hydrogel, and the usual mechanical strength of hydrogel of this method preparation
It is lower.
In recent years the research new direction of drug controlled release technology by be macromolecular drug perfect use, with social section
The progress of technology, completely new drug sustained release system will be increasingly prominent to the importance of bio-medical field.Indomethacin (IND)
Belong to non-steroidal drug, the entitled 1-(of chemistry is to chlorobenzene formacyl) -5- methoxyl group -2 methyl indole -3- acetic acid indoles second
Acid derivative also known as indocin.Due to being widely used in treating wound with very effective antipyretic, analgesia and anti-inflammatory activity
With the diseases such as rheumatoid arthritis.Indomethacin is a kind of acid dewatering medicament, and dissolubility is poor under water and acid pH, but energy
It is quickly dissolved in alkali.Due to the difference that dissolves in the stomach, IND may be contacted due to the long-time with mucous membrane and be shown low oral bio
Using effect or it may cause side effect.Therefore, exploitation, which has, increases Indomethacin solubility, improves bioavilability and subtract
The novel form of few adverse reaction arouses widespread concern, such as hydrogel slow-released carrier.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of preparation sides of high-biocompatibility pharmaceutical carrier hydrogel
Method:
The present invention chooses sodium alginate, chitosan as raw material, utilizes the electrostatic between two kinds of oppositely charged polyelectrolyte
Interaction prepares high intensity hydrogel；The addition of carboxymethyl nano-cellulose improves the pH sensibility of hydrogel entirety simultaneously
And mechanical property.Furthermore the hydrogel after oxidation is conducive to improve the degeneration energy of hydrogel.Finally, the Compound Water
Gel has certain Indomethacin slow release effect.Specifically:
Step (1): carboxymethyl nano-cellulose, chitosan, stirring to carboxymethyl nanometer are sequentially added in sodium alginate soln
Cellulose, chitosan are dispersed in sodium alginate soln, and it is mixed to obtain sodium alginate-carboxymethyl nano-cellulose-chitosan
Close liquid.
Step (2): sodium alginate made from step (1)-carboxymethyl nano-cellulose-chitosan mixed liquor is injected into mold
In, it impregnates in an acidic solution, keeps sodium alginate and chitosan full cross-linked, obtain sodium alginate-carboxymethyl nano-cellulose-
Chitosan composite hydrogel.
Step (3): sodium alginate made from step (2)-carboxymethyl nano-cellulose-chitosan composite hydrogel is impregnated
It aoxidizes, is freeze-dried spare in sodium periodate solution.
Step (4): the composite hydrogel after oxidation, drying in step (3) is immersed in the indoles for having dissolved doses
In the ammonium hydroxide of the pungent drug of U.S., drying obtains Indomethacin load composite hydrogel.
Furtherly, sodium alginate described in step (1)-carboxymethyl nano-cellulose-chitosan mixed liquor each group sub-prime
Measure degree are as follows: sodium alginate 2 ~ 20%, carboxymethyl nano-cellulose 0.1 ~ 5%, chitosan 2 ~ 20%.
Furtherly, sodium alginate described in step (1)-carboxymethyl nano-cellulose-chitosan mixed liquor high speed point
Dissipate machine dispersion, revolving speed 1000r/min, 1 ~ 5h of jitter time.
Furtherly, the molar concentration of acid solution described in step (2) is 2mol/L, and soaking time is for 24 hours.
Furtherly, sodium periodate solution concentration described in step (3) is 0.1mol/L, 4 °C of shading oxidations in refrigerator
12h。
Furtherly, ammonium hydroxide molar concentration described in step (4) is 0.05mol/L, 0.1 ~ 1g/ of Indomethacin content of drug
Ml, adsorption time 12 ~ for 24 hours.
Beneficial effects of the present invention:
One, the present invention use sodium alginate, chitosan, carboxymethyl nano-cellulose to prepare medicine for raw material and carry hydrogel, have
Preferable environment friendly, biocompatibility；
Second, preparing hydrogel using the electrostatic interaction between two kinds of oppositely charged polyelectrolyte, reaction condition is mild,
The chemical substances such as crosslinking agent, photoinitiator are not needed；
Thirdly, the addition of carboxymethyl nano-cellulose improves the pH sensibility of hydrogel entirety and mechanical property, oxidation mention
The high degeneration energy of hydrogel.
Specific embodiment
Below with reference to embodiment, the invention will be further described.
Embodiment 1:
Firstly, sequentially adding 0.5% carboxymethyl nano-cellulose, 2% chitosan in 2% sodium alginate soln, height is used
Fast dispersion machine dispersion, revolving speed 1000r/min, dispersion 3h to carboxymethyl nano-cellulose, chitosan are dispersed in sodium alginate
In solution, sodium alginate-carboxymethyl nano-cellulose-chitosan mixed liquor is obtained；Secondly, obtained mixed liquor is injected mold
In, it is immersed in the hydrochloric acid solution of 2mol/L for 24 hours, keeps sodium alginate and chitosan full cross-linked；Again, composite hydrogel is soaked
Bubble is in the sodium periodate solution of 0.1mol/L, and 4 °C of shadings aoxidize 12h in refrigerator, is freeze-dried spare；Finally, will aoxidize,
Composite hydrogel after drying is immersed in 12h in the ammonium hydroxide of the Indomethacin drug of 0.4g/ml, and drying obtains Indomethacin load
Composite hydrogel.
Embodiment 2:
Firstly, sequentially adding 3.6% carboxymethyl nano-cellulose, 15% chitosan in 10% sodium alginate soln, use
High speed disperser dispersion, revolving speed 1000r/min, dispersion 4h to carboxymethyl nano-cellulose, chitosan are dispersed in alginic acid
In sodium solution, sodium alginate-carboxymethyl nano-cellulose-chitosan mixed liquor is obtained；Secondly, obtained mixed liquor is injected mould
It in tool, is immersed in the hydrochloric acid solution of 2mol/L for 24 hours, keeps sodium alginate and chitosan full cross-linked；Again, by composite hydrogel
It is immersed in the sodium periodate solution of 0.1mol/L, 4 °C of shadings aoxidize 12h in refrigerator, are freeze-dried spare；Finally, by oxygen
18h in the ammonium hydroxide for the Indomethacin drug that composite hydrogel after changing, being dry is immersed in 0.6g/ml, drying obtain Indomethacin
Load composite hydrogel.
Embodiment 3:
Firstly, sequentially adding 5% carboxymethyl nano-cellulose, 20% chitosan in 20% sodium alginate soln, height is used
Fast dispersion machine dispersion, revolving speed 1000r/min, dispersion 5h to carboxymethyl nano-cellulose, chitosan are dispersed in sodium alginate
In solution, sodium alginate-carboxymethyl nano-cellulose-chitosan mixed liquor is obtained；Secondly, obtained mixed liquor is injected mold
In, it is immersed in the hydrochloric acid solution of 2mol/L for 24 hours, keeps sodium alginate and chitosan full cross-linked；Again, composite hydrogel is soaked
Bubble is in the sodium periodate solution of 0.1mol/L, and 4 °C of shadings aoxidize 12h in refrigerator, is freeze-dried spare；Finally, will aoxidize,
Composite hydrogel after drying is immersed in the ammonium hydroxide of the Indomethacin drug of 0.8g/ml for 24 hours, and drying obtains Indomethacin load
Composite hydrogel.
Claims (6)
1. a kind of preparation method of high-biocompatibility pharmaceutical carrier hydrogel, it is characterised in that include the following steps:
Step (1): carboxymethyl nano-cellulose, chitosan, stirring to carboxymethyl nanometer are sequentially added in sodium alginate soln
Cellulose, chitosan are dispersed in sodium alginate soln, and it is mixed to obtain sodium alginate-carboxymethyl nano-cellulose-chitosan
Close liquid；
Step (2): sodium alginate made from step (1)-carboxymethyl nano-cellulose-chitosan mixed liquor is injected in mold,
It impregnates in an acidic solution, keeps sodium alginate and chitosan full cross-linked, obtain sodium alginate-carboxymethyl nano-cellulose-shell
Glycan composite hydrogel；
Step (3): sodium alginate made from step (2)-carboxymethyl nano-cellulose-chitosan composite hydrogel is immersed in height
It aoxidizes, is freeze-dried spare in sodium iodide solution；
Step (4): the composite hydrogel after oxidation, drying in step (3) is immersed in the Indomethacin for having dissolved doses
In the ammonium hydroxide of drug, drying obtains Indomethacin load composite hydrogel.
2. a kind of preparation method of high-biocompatibility pharmaceutical carrier hydrogel according to claim 1, which is characterized in that
Sodium alginate described in step (1)-carboxymethyl nano-cellulose-chitosan mixed liquor each component content are as follows: sodium alginate 2 ~
20%, carboxymethyl nano-cellulose 0.1 ~ 5%, chitosan 2 ~ 20%.
3. a kind of preparation method of high-biocompatibility pharmaceutical carrier hydrogel according to claim 1, which is characterized in that
Sodium alginate described in step (1)-carboxymethyl nano-cellulose-chitosan mixed liquor is dispersed with high speed disperser, revolving speed
1000r/min, 1 ~ 5h of jitter time.
4. a kind of preparation method of high-biocompatibility pharmaceutical carrier hydrogel according to claim 1, which is characterized in that
The molar concentration of acid solution described in step (2) is 2mol/L, and soaking time is for 24 hours.
5. a kind of preparation method of high-biocompatibility pharmaceutical carrier hydrogel according to claim 1, which is characterized in that
Sodium periodate solution concentration described in step (3) is 0.1mol/L, and 4 °C of shadings aoxidize 12h in refrigerator.
6. a kind of preparation method of high-biocompatibility pharmaceutical carrier hydrogel according to claim 1, which is characterized in that
Ammonium hydroxide molar concentration described in step (4) be 0.05mol/L, Indomethacin 0.1 ~ 1g/ml of content of drug, adsorption time 12 ~
24h。
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Cited By (5)
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| CN111228213A (en) * | 2020-02-21 | 2020-06-05 | 浙江理工大学 | Preparation method and application of biocompatible nano composite hydrogel |
| CN111920759A (en) * | 2020-07-17 | 2020-11-13 | 华南农业大学 | Gastrointestinal tract combined administration gel for livestock and preparation method and application thereof |
| CN114316375A (en) * | 2021-09-22 | 2022-04-12 | 安徽农业大学 | Hierarchical pore structure composite aerogel and preparation method thereof |
| CN115124739A (en) * | 2022-07-12 | 2022-09-30 | 自然资源部第三海洋研究所 | Injectable marine polysaccharide full-physical crosslinked hydrogel and preparation method thereof |
| CN115530222A (en) * | 2022-09-19 | 2022-12-30 | 福建农林大学 | Food fresh-keeping pad with slow-release antibacterial and antioxidant functions and preparation method thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228213A (en) * | 2020-02-21 | 2020-06-05 | 浙江理工大学 | Preparation method and application of biocompatible nano composite hydrogel |
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| CN115124739A (en) * | 2022-07-12 | 2022-09-30 | 自然资源部第三海洋研究所 | Injectable marine polysaccharide full-physical crosslinked hydrogel and preparation method thereof |
| CN115530222A (en) * | 2022-09-19 | 2022-12-30 | 福建农林大学 | Food fresh-keeping pad with slow-release antibacterial and antioxidant functions and preparation method thereof |
| CN115530222B (en) * | 2022-09-19 | 2024-01-26 | 福建农林大学 | Food fresh-keeping pad with slow-release antibacterial and antioxidant functions and preparation method thereof |
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