CN109908328A - Nanometer percutaneous technique is used to improve the eye sticker and preparation method thereof of eyes xerophthalmia - Google Patents
Nanometer percutaneous technique is used to improve the eye sticker and preparation method thereof of eyes xerophthalmia Download PDFInfo
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- CN109908328A CN109908328A CN201910225899.XA CN201910225899A CN109908328A CN 109908328 A CN109908328 A CN 109908328A CN 201910225899 A CN201910225899 A CN 201910225899A CN 109908328 A CN109908328 A CN 109908328A
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- xerophthalmia
- eye sticker
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- sodium alginate
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- 210000001508 eye Anatomy 0.000 title claims abstract description 53
- 208000005494 xerophthalmia Diseases 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000000661 sodium alginate Substances 0.000 claims abstract description 21
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 21
- 238000003756 stirring Methods 0.000 claims abstract description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000007788 liquid Substances 0.000 claims abstract description 15
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 15
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims abstract description 14
- 239000001110 calcium chloride Substances 0.000 claims abstract description 14
- 229910001628 calcium chloride Inorganic materials 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 14
- 239000000843 powder Substances 0.000 claims abstract description 12
- 229920001661 Chitosan Polymers 0.000 claims abstract description 9
- 239000002105 nanoparticle Substances 0.000 claims abstract description 8
- 239000000243 solution Substances 0.000 claims abstract description 7
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims abstract description 6
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims abstract description 6
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- 238000013019 agitation Methods 0.000 claims abstract description 6
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- 238000005119 centrifugation Methods 0.000 claims abstract description 6
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- 238000001914 filtration Methods 0.000 claims abstract description 6
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- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 5
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 5
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 5
- 235000012680 lutein Nutrition 0.000 claims description 5
- 229960005375 lutein Drugs 0.000 claims description 5
- 239000001656 lutein Substances 0.000 claims description 5
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 claims description 5
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- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 claims description 5
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- 229940045997 vitamin a Drugs 0.000 claims description 5
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 claims description 5
- 229930003427 Vitamin E Natural products 0.000 claims description 4
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 4
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- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims 1
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- Medicinal Preparation (AREA)
Abstract
The invention discloses the eye stickers and preparation method thereof that nanometer percutaneous technique is used to improve eyes xerophthalmia.Include the following steps: for sodium alginate and calcium chloride to be dissolved in distilled water respectively；Compositions useful is dissolved in sodium alginate stock solution, is stirred；Calcium chloride water is added in solution under agitation, and continues stirring and completes pregelatinized process；It dissolves chitosan in acetic acid, and is added in pregel, form nano particle；Dispersion, with centrifugation freeze-drying at powder；Above-mentioned powder is redissolved, and borneol is added and menthol stirs and evenly mixs, filtering, sterilizing obtains eye sticker liquid；Non-woven fabrics is put into eye sticker liquid and is infiltrated, the eye sticker for the xerophthalmia that is eased.Present invention uses what can be degraded in vivo, the chitin-sodium alginate nano-carrier of good biocompatibility is carried in eye sticker, the storage stability of composition is not only improved, while wherein effective component can play the effect for further improving xerophthalmia and visual fatigue with slow release.
Description
Technical field
The present invention relates to a kind of eye stickers, and in particular to nanometer percutaneous technique is used to improve the eye sticker and its system of eyes xerophthalmia
Preparation Method.
Background technique
Xerophthalmia is since the natural function and protection mechanism of external eyes generate various obstacles, and tear film is unstable when causing to twinkle
A kind of eye surface diseases.Generally acknowledged xerophthalmia producing cause such as fluidity tear generates reduction, mucous secretion exception and tarsus at present
Gland dysfunction etc., leads to the absolute and relative shortage of the fluidity ingredient of tear film, ocular tear abnormal distribution, and tear evaporation increases
And it moisten cornea and conjunctiva cannot normally and the general name that ocular epithelium does the one group of clinical disease become occur.Symptom passes through
Treatment can be alleviated, it can be difficult to curing completely, common treatment means are soaked using common water borne eye drops, lubricate eye
Ball, to alleviate ophthalmic uncomfortable；Or tear substitutes artificial tears are applied, but their common disadvantages are that preparation is in ocular
Residence time is short, eliminates quickly, bioavilability is not high.In recent years, with the hair of the electronic products such as TV, computer, mobile phone
Exhibition, eye health are increasingly becoming the social concern to become increasingly conspicuous.Electronic product is used for a long time, patients with dry eye becomes in cumulative year after year
Gesture and to become younger development, in time prevention alleviate xerophthalmia, can reduce ophthalmic uncomfortable.
Nano-carrier currently used for ocular drug delivery mainly has micro emulsion, liposome, lipid cubic crystal, vesica, water-setting
Glue etc..Drug can extend drug in the delay of eye after nano-carrier contains, while promote drug cornea to penetrate, and improve
Its bioavilability.Chitosan is considered as a kind of nontoxic to the human body, nonirritant, polymer of bio-compatible, by
Japan, Italy and Finland's approval are used for food, and U.S. FDA also has been approved by it and is used in wound dressing auxiliary material, have good
Biodegradability, have antibacterial effect, to medicament slow release treatment have certain synergism.Chitosan be in nature only
One alkaline polysaccharide easily forms intramolecular, divides due to containing great amount of hydroxy group, acetylamino, amino groups in its molecular structure
Ammonia key between son is in close crystalline structure, and crystallinity is higher, thus not soluble in water or organic solvent, dissolves in diluted acid, molten
Liquid is in thick.Hydroxyl and amino Nature comparison in chitosan molecule is active, may be trimmed, activates and is coupled.Alginic acid
Sodium is a kind of natural polysaccharide extracted from kelp, passes through (1,4) glucosides by beta-D-mannuronic acid and α-L- guluronic acid
Key links.In aqueous solution, carboxylic ions are negatively charged for sodium alginate, show polyanionic polymer characteristic, and two
Person forms a kind of compound polyelectrolyte for being not dissolved in water by charge interaction.In addition, the two passes through electrostatic interaction, ammonia
The modes such as key effect or crosslinking, form and seep miscellaneous interpenetrating networks, the stability and carrying drug ratio of pharmaceutical carrier can be improved, improve carrier
Mechanical property.
Summary of the invention
The present invention provides the eye sticker and preparation method thereof that nanometer percutaneous technique is used to improve eyes xerophthalmia, and the eye sticker is main
Ingredient is the compositions useful and chitin-sodium alginate nano-carrier for treating xerophthalmia.
Technical solution of the present invention is as follows.
Nanometer percutaneous technique is used to improve the preparation method of the eye sticker of eyes xerophthalmia, includes the following steps:
(1) sodium alginate and calcium chloride are dissolved in distilled water respectively, obtain sodium alginate stock solution and calcium chloride water；
(2) compositions useful is dissolved in sodium alginate stock solution, stirs 0.5-2h；
(3) it will be added in calcium chloride water 30min-60min in step (2) solution under agitation, and continue to stir
15min-60min completes pregelatinized process；
(4) it dissolves chitosan in the acetic acid that 5-20ml mass percent concentration is 1-2%, and it is pre- solidifying that step (3) is added dropwise
In glue, continues to stir 30min-60min, form nano particle；
(5) ultrasonic disperse prevents from assembling, with 10000rpm-15000 centrifugation 20min-60min freeze-drying at powder；
(6) above-mentioned powder is redissolved, and borneol is added and menthol stirs and evenly mixs, filtering, sterilizing obtains eye sticker liquid；
(7) non-woven fabrics is put into the eye sticker liquid that step (6) obtains and is infiltrated, packed, obtain the eye sticker for alleviating xerophthalmia.
In the above method, the compositions useful includes ciclosporin A, epidermal growth factor, vitamin E, lutein, fructus lycii
One or more of extract, cassia seed extract, vitamin A.
In the above method, the total weight based on composition, the vitamin A, vitamin E, ciclosporin A, epidermal growth factor
Son and the mass content of lutein in the composition are respectively 0.01-100%；The wolfberry fruit extract, cassia seed extract it is total
Mass content is 0.01 ~ 15%.
The compositions useful nano-carrier that the present invention wraps up treatment xerophthalmia can transdermal alleviation symptom.Present invention uses
It can degrade in vivo, the chitin-sodium alginate nano-carrier of good biocompatibility is carried in eye sticker, is not only improved
The storage stability of composition, at the same wherein effective component can with slow release, can play further improve xerophthalmia and
The effect of visual fatigue.
Compared with prior art, present invention has an advantage that
Present invention uses what can be degraded in vivo, the chitin-sodium alginate nano-carrier of good biocompatibility is loaded
In the storage stability in eye sticker, not only improving composition, at the same wherein effective component can with slow release, can play into
The effect of one step improvement xerophthalmia and visual fatigue.Effective nano drug-carrying composition can adjust the nerve on eyes and head well,
Muscle, blood vessel promotes the blood circulation on eye and head, thus achieve the purpose that loosen, it is uncomfortable to various eyes, as eyes are dry
The symptoms such as puckery, eye fatigue, hypopsia, photophobia shed tears, myopia, presbyopia, glaucoma, intraocular hypertension, cataract have very
Good alleviation and adjustment effect.
Detailed description of the invention
Fig. 1 is the prepared chitin-sodium alginate nano-carrier grain-size graph come out of real embodiment 3.
Fig. 2 be by nanoparticle cyclosporin A in ultraviolet spectrophotometry detection example 1 at 37 DEG C in pH7.4PBS
Slow release curve graph.
Specific embodiment
The present invention will be further described with reference to embodiments.
Wolfberry fruit extract purchase in the present embodiment buys Yu Langlin in bright woods biological (NAT-115), cassia seed extract
Biological (NAT-041).
Embodiment 1
(1) 0.1g sodium alginate and 0.01g calcium chloride are dissolved in respectively in the distilled water of 10ml.
(2) by 0.5ug epidermal growth factor and 1mg ciclosporin A, 0.05mg wolfberry fruit extract is dissolved in sodium alginate deposit
In liquid, 1h is stirred.
(3) it will be added in calcium chloride water 30min in above-mentioned 2 solution under agitation, and continue to stir 15min
Complete pregelatinized process.
(4) next 0.01g chitosan is dissolved in the acetic acid (mass percent concentration 2%) of 10ml, and added dropwise
Enter in above-mentioned 3 pregel, continues to stir 30min, form nano particle.
(5) ultrasonic disperse 20min prevents from assembling, with 11000rpm centrifugation 40min freeze-drying at powder.
(6) above-mentioned powder is redissolved, and borneol is added and menthol stirs and evenly mixs, filtering, sterilizing obtains eye sticker liquid.
(7) non-woven fabrics is put into the eye sticker liquid that step (6) obtains and is infiltrated, packed, obtain the eye for alleviating xerophthalmia
Patch.
Fig. 2 be by nanoparticle cyclosporin A in ultraviolet spectrophotometry detection example 1 at 37 DEG C in pH7.4PBS
Slow release curve graph, cyclosporine can realize that slow release, the cumulative release of 30h are 40% in nano-carrier.
Embodiment 2
(1) 0.1g sodium alginate and 0.01g calcium chloride are dissolved in respectively in the distilled water of 10ml.
(2) 0.05mg wolfberry fruit extract, 0.1mg cassia seed extract and 1mg ciclosporin A are dissolved in sodium alginate deposit
In liquid, 1h is stirred.
(3) it will be added in calcium chloride water 30min in above-mentioned 2 solution under agitation, and continue to stir 15min
Complete pregelatinized process.
(4) next 0.01g chitosan is dissolved in the acetic acid (2%) of 10ml, and is added dropwise in above-mentioned 3 pregel,
Continue to stir 30min, forms nano particle.
(5) ultrasonic disperse 30min prevents from assembling, with 11000rpm centrifugation 40min freeze-drying at powder.
(6) above-mentioned powder is redissolved, and borneol is added and menthol stirs and evenly mixs, filtering, sterilizing obtains eye sticker liquid.
(7) non-woven fabrics is put into the eye sticker liquid that step (6) obtains and is infiltrated, packed, obtain the eye for alleviating xerophthalmia
Patch.
Embodiment 3
For improving the eye sticker nanometer percutaneous technique of eyes xerophthalmia
(1) 0.1g sodium alginate and 0.01g calcium chloride are dissolved in respectively in the distilled water of 10ml.
(2) by 0.05ug epidermal growth factor, 0.01mg lutein and 1mg vitamin A, the dissolution of 0.05mg wolfberry fruit extract
In sodium alginate stock solution, 1h is stirred.
(3) it will be added in calcium chloride water 30min in above-mentioned 2 solution under agitation, and continue to stir 15min
Complete pregelatinized process.
(4) next 0.02g chitosan is dissolved in the acetic acid (2%) of 10ml, and is added dropwise in above-mentioned 3 pregel,
Continue to stir 30min, forms nano particle.
(5) ultrasonic disperse 10min prevents from assembling, with 11000rpm centrifugation 40min freeze-drying at powder.
(6) above-mentioned powder is redissolved, and borneol is added and menthol stirs and evenly mixs, filtering, sterilizing obtains eye sticker liquid.
(7) non-woven fabrics is put into the eye sticker liquid that step (6) obtains and is infiltrated, packed, obtain the eye for alleviating xerophthalmia
Patch.
Fig. 1 is the prepared chitin-sodium alginate nano-carrier grain-size graph come out of real embodiment 3, it can be seen that partial size exists
190nm or so, PDI 0.1, size is uniform, is uniform dispersion, is easy to Transdermal absorption.
The above embodiment of the present invention be only to clearly illustrate example of the present invention, and not be to the present invention
Embodiment restriction.For those of ordinary skill in the art, it can also make on the basis of the above description
Other various forms of variations or variation.There is no necessity and possibility to exhaust all the enbodiments.It is all of the invention
Made any modifications, equivalent replacements, and improvements etc., should be included in the protection of the claims in the present invention within spirit and principle
Within the scope of.
Claims (4)
1. the preparation method that nanometer percutaneous technique is used to improve the eye sticker of eyes xerophthalmia, which comprises the steps of:
(1) sodium alginate and calcium chloride are dissolved in distilled water respectively, obtain sodium alginate stock solution and calcium chloride water；
(2) compositions useful is dissolved in sodium alginate stock solution, stirs 0.5-2h；
(3) it will be added in calcium chloride water 30min-60min in step (2) solution under agitation, and continue to stir
15min-60min completes pregelatinized process；
(4) it dissolves chitosan in the acetic acid that 5-20ml mass percent concentration is 1-2%, and it is pre- solidifying that step (3) is added dropwise
In glue, continues to stir 30min-60min, form nano particle；
(5) ultrasonic disperse prevents from assembling, with 10000rpm-15000 centrifugation 20min-60min freeze-drying at powder；
(6) above-mentioned powder is redissolved, and borneol is added and menthol stirs and evenly mixs, filtering, sterilizing obtains eye sticker liquid；
(7) non-woven fabrics is put into the eye sticker liquid that step (6) obtains and is infiltrated, packed, obtain the eye sticker for alleviating xerophthalmia.
2. nanometer percutaneous technique is used to improve the preparation method of the eye sticker of eyes xerophthalmia, feature according to claim 1
It is, the compositions useful includes ciclosporin A, epidermal growth factor, vitamin E, lutein, wolfberry fruit extract, cassia seed
One or more of extract, vitamin A.
3. nanometer percutaneous technique is used to improve the preparation method of the eye sticker of eyes xerophthalmia, feature according to claim 2
It is, the total weight based on composition, the vitamin A, vitamin E, ciclosporin A, epidermal growth factor and lutein are in group
The mass content closed in object is respectively 0.01-100%；The wolfberry fruit extract, the gross mass content of cassia seed extract are 0.01
~15%。
4. nanometer percutaneous technique is prepared for improving the eye of eyes xerophthalmia in any one of claim 1 ~ 3 preparation method
Patch.
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| CN114028363A (en) * | 2021-11-25 | 2022-02-11 | 上海婷伊美科技有限公司 | Gold eye patch for xerophthalmia and preparation method thereof |
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