CN103083244A - Lysozyme curcumin nanoparticle - Google Patents
Lysozyme curcumin nanoparticle Download PDFInfo
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- CN103083244A CN103083244A CN2011103431852A CN201110343185A CN103083244A CN 103083244 A CN103083244 A CN 103083244A CN 2011103431852 A CN2011103431852 A CN 2011103431852A CN 201110343185 A CN201110343185 A CN 201110343185A CN 103083244 A CN103083244 A CN 103083244A
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- curcumin
- lysozyme
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- nanoparticle
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- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 title claims abstract description 202
- 229940109262 curcumin Drugs 0.000 title claims abstract description 101
- 235000012754 curcumin Nutrition 0.000 title claims abstract description 101
- 239000004148 curcumin Substances 0.000 title claims abstract description 101
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 title claims abstract description 101
- 102000016943 Muramidase Human genes 0.000 title claims abstract description 63
- 108010014251 Muramidase Proteins 0.000 title claims abstract description 63
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 title claims abstract description 63
- 229960000274 lysozyme Drugs 0.000 title claims abstract description 63
- 235000010335 lysozyme Nutrition 0.000 title claims abstract description 63
- 239000004325 lysozyme Substances 0.000 title claims abstract description 63
- 239000002105 nanoparticle Substances 0.000 title abstract description 12
- 239000008187 granular material Substances 0.000 claims description 56
- 229920001223 polyethylene glycol Polymers 0.000 claims description 33
- 239000004626 polylactic acid Substances 0.000 claims description 30
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 27
- 239000002202 Polyethylene glycol Substances 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 15
- 229920001577 copolymer Polymers 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 13
- 239000003814 drug Substances 0.000 abstract description 31
- 229940079593 drug Drugs 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 9
- 230000008685 targeting Effects 0.000 abstract description 8
- 210000000056 organ Anatomy 0.000 abstract description 6
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 3
- 230000001934 delay Effects 0.000 abstract description 2
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 230000001476 alcoholic effect Effects 0.000 description 10
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 10
- 229920000053 polysorbate 80 Polymers 0.000 description 10
- 210000003734 kidney Anatomy 0.000 description 9
- 206010016654 Fibrosis Diseases 0.000 description 5
- 230000004761 fibrosis Effects 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229920000151 polyglycol Polymers 0.000 description 3
- 239000010695 polyglycol Substances 0.000 description 3
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
- 239000000400 angiotensin II type 1 receptor blocker Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000003584 mesangial cell Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 101150033765 BAG1 gene Proteins 0.000 description 1
- 241000190633 Cordyceps Species 0.000 description 1
- 244000163122 Curcuma domestica Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101001087422 Homo sapiens Tyrosine-protein phosphatase non-receptor type 13 Proteins 0.000 description 1
- 102100033014 Tyrosine-protein phosphatase non-receptor type 13 Human genes 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- -1 contains: ACEI Substances 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 229920001553 poly(ethylene glycol)-block-polylactide methyl ether Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides a lysozyme curcumin nanoparticle, which comprises a curcumin nanoparticle and lysozyme. The lysozyme is jointed with the curcumin through a covalent bond. The lysozyme curcumin nanoparticle provided in the invention improves the drug renal interstitial targeting property, effectively delays drug release, enhances drug stability, covers up peculiar drug smell, and reduces the toxic and side effects of the drug on the gastrointestinal tract. Drug release is controlled in a target organ, so that the efficacy of the nanoparticle is enhanced, and at the same time, adverse reactions of other body organs and cells to the nanoparticle are reduced. Thus, a curcumin Chinese herbal preparation can be developed into a safe, stable and effective novel traditional Chinese medicine.
Description
Technical field
The present invention relates to a kind of curcumin nano granule, relate in particular to a kind of lysozyme curcumin nano granule that is used for the treatment of renal fibrosis.
Background technology
The kidney region fibrosis pathomechanism has the characteristics of too many levels and many target spots, there is no at present special effective medicine, and adopts aggregate measures more.Traditional medicine mainly contains: ACEI, AT_1 receptor antagonist (AT1RA), soluble T GF-β antibody etc.Yet because the targeting of conventional medicament is poor, so the therapeutic effect of fibrosis is poor, waste a large amount of medical resources.
There is long history in China in control kidney region fibrosis disease, studying at present more Chinese medicine has curcumin, Radix Salviae Miltiorrhizae, Radix Et Rhizoma Rhei, Cordyceps, slow kidney health, DAHUANG SHUCHONG WAN etc.Curcumin (curcumin, CM) is the main effective ingredient that extracts from plant Rhizoma Curcumae Longae Curcuma longa L., has the effects such as antitumor, antiinflammatory and blood fat reducing.At present existing scholar confirms that curcumin can disturb the MCs cell cycle distribution, have antiproliferative and apoptosis-induced effect, delay effect (Peng Wen, Li Qi, the Fu Wencheng etc. " curcumin and the OX-LDL impact on Apoptosis of Mesangial Cells and FAP-1 and bag-1 expression " of glomerular sclerosis, Shanghai Univ. of Traditional Chinese Medicine's journal, 2007,21 (4): 54-57; Wang Hao, Fu Wencheng, Wang Yunman etc. " impact on mesangial cell proliferation and apoptosis of curcumin and OxLDL ELISA " shanghai Medicine, 2007,30 (7): 545-547.).Yet the blood-activating and stasis-removing that contains at present curcumin still lacks clear and definite fibrosis mechanism, and targeting is relatively poor simultaneously.
Nanoparticle has small-size effect, and skin effect and very strong adsorptivity and biological activity show many excellent properties and brand-new function, can be used as carrier, change medicine distribution in vivo, improved drug absorption availability and stability, improve pharmaceutical properties and targeting.In some researchs abroad, have in prior art curcumin is written into nanoparticle treatment rat cystic fibrosis, realized targeted therapy (the Cartiera MS of curcumin fibrosis, Ferreira EC, Caputo C, et al. Partial correction of cystic fibrosis defects with PLGA nanoparticles.encapsulating curcumin.Mol Pharm. 2010 Feb 1; 7 (1): 86-93.).But kidney is the vitals of human body, has the balanced action that keeps water, electrolyte, nutrient substance and metabolite.Use at present more ripe curcumin Polyethylene Glycol (polyglycol, PEG) and polylactic acid (PLA) block copolymer there is no good kidney targeting for matter between kidney in prior art.
Summary of the invention
Therefore, find out the present invention in order to solve the above-mentioned problem of mentioning, the purpose of this invention is to provide a kind of lysozyme that utilizes as the lysozyme curcumin nano granule of the curcumin copolymerization PEG-PLA nano-particle of kidney targeting vector.
A kind of lysozyme curcumin nano granule comprises the curcumin nano granule, wherein also contains lysozyme, and described lysozyme engages with described curcumin by covalent bond.
In a preferred embodiment of the present invention, the particle diameter of described lysozyme curcumin nano granule is 105 ~ 135 nanometers.
In another preferred embodiment of the present invention, the envelop rate of described lysozyme curcumin nano granule is 65.78 ~ 76.36%.
In another preferred embodiment of the present invention, the content of described curcumin is 2.69 ~ 3.88% of quality.
In another preferred embodiment of the present invention, the carrier of described curcumin nano granule is the copolymer of Polyethylene Glycol (polyglycol, PEG) and polylactic acid (PLA).
In another preferred embodiment of the present invention, the quality percentage composition of described curcumin: PEG:PLA is than being 1:5 ~ 7:10 ~ 14.
In another preferred embodiment of the present invention, the quality percentage composition of described curcumin: lysozyme: PEG:PLA is than being 1:4 ~ 80:5 ~ 7:10 ~ 14.
Lysozyme curcumin nano granule in the present invention has improved matter targeting between the kidney of medicine, effectively delays drug release, improves the stability of medicine, covers drug flavor, reduces medicine to the toxic and side effects of gastrointestinal tract etc.Control release in target organ, its drug effect is strengthened, reduce simultaneously the untoward reaction to other organs of human body and cell, make the curcumin Chinese medicine preparation can develop into safety, stable, effective new medicine preparation.
The specific embodiment
The present invention is further elaborated below with reference to specific embodiment.
A kind of lysozyme curcumin nano granule of the present invention wherein not only contains the curcumin nano granule, also contains lysozyme, and lysozyme engages with curcumin by covalent bond.
Curcumin in the present invention utilizes nano-particle as carrier, can effectively utilize the small-size effect of nano-particle, skin effect and very strong adsorptivity and biological activity, change medicine distribution in vivo, drug absorption availability and stability have been improved, improve pharmaceutical properties, alleviate or avoid toxic and side effects.Utilize simultaneously the covalently bound method of chemical bond link lysozyme and curcumin, improve matter targeting between the kidney of medicine, effectively delay drug release, improve the stability of medicine, cover drug flavor, reduce medicine to the toxic and side effects of gastrointestinal tract etc.Control release in target organ, its drug effect is strengthened, reduce simultaneously the untoward reaction to other organs of human body and cell, make the curcumin Chinese medicine preparation can develop into safety, stable, effective new medicine preparation.
In an embodiment of the present invention, the particle diameter of lysozyme curcumin nano granule is 105 ~ 135 nanometers, and envelop rate is 65.78 ~ 76.36%, and the content of curcumin is 2.69 ~ 3.88% of quality.
In another embodiment of the present invention, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol (polyglycol, PEG) and polylactic acid (PLA).Wherein the quality percentage composition of preferred curcumin: PEG:PLA is than being 1:5 ~ 7:10 ~ 14.Certainly in other embodiments, can use other curcumin nano objects or other mass ratio, as long as an effective curcumin nano particulate vector can be provided, the present embodiment does not limit this yet.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid,
Embodiment 1
A kind of particle diameter of lysozyme curcumin nano granule is 120 nanometers, the effective diameter normal distribution; Envelop rate is 67.76%; The content of curcumin is 3.26% of quality; Polydispersity index 0.252 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 50:1:1.
Embodiment 2
A kind of particle diameter of lysozyme curcumin nano granule is 115 nanometers, the effective diameter normal distribution; Envelop rate is 64.36%; The content of curcumin is 2.69% of quality; Polydispersity index 0.253 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 20:1:2.5.
Embodiment 3
A kind of particle diameter of lysozyme curcumin nano granule is 129 nanometers, the effective diameter normal distribution; Envelop rate is 64.58%; The content of curcumin is 2.79% of quality; Polydispersity index 0.252 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 60:1:2.
Embodiment 4
A kind of particle diameter of lysozyme curcumin nano granule is 134 nanometers, the effective diameter normal distribution; Envelop rate is 72.56%; The content of curcumin is 3.48% of quality; Polydispersity index 0.255 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 80:1:2.
Embodiment 5
A kind of particle diameter of lysozyme curcumin nano granule is 123 nanometers, the effective diameter normal distribution; Envelop rate is 71.36%; The content of curcumin is 3.88% of quality; Polydispersity index 0.255 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 40:1:2.
Embodiment 6
A kind of particle diameter of lysozyme curcumin nano granule is 131 nanometers, the effective diameter normal distribution; Envelop rate is 70.66%; The content of curcumin is 3.06% of quality; Polydispersity index 0.251 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 60:1:2.
Embodiment 7
A kind of particle diameter of lysozyme curcumin nano granule is 133 nanometers, the effective diameter normal distribution; Envelop rate is 68.74%; The content of curcumin is 3.56% of quality; Polydispersity index 0.253 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 70:1:2.
Embodiment 8
A kind of particle diameter of lysozyme curcumin nano granule is 128 nanometers, the effective diameter normal distribution; Envelop rate is 63.24%; The content of curcumin is 3.15% of quality; Polydispersity index 0.253 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 50:1:2.
Embodiment 9
A kind of particle diameter of lysozyme curcumin nano granule is 135 nanometers, the effective diameter normal distribution; Envelop rate is 65.78%; The content of curcumin is 2.80% of quality; Polydispersity index 0.254 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 10:1:2.
Embodiment 10
A kind of particle diameter of lysozyme curcumin nano granule is 105 nanometers, the effective diameter normal distribution; Envelop rate is 76.36%; The content of curcumin is 2.78% of quality; Polydispersity index 0.251 all presents the feature of slow release in medium 20% alcoholic solution and 0.25%Tween-80 solution, the prominent phenomenon of releasing does not occur.
Wherein, the carrier of curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid, and in lysozyme curcumin nano granule, the quality percentage composition of lysozyme: PEG:PLA is than being 50:1:2.
Above specific embodiments of the invention are described in detail, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and substituting also all among category of the present invention.Therefore, not breaking away from impartial conversion and the modification of doing under the spirit and scope of the present invention, all should contain within the scope of the invention.
Claims (7)
1. a lysozyme curcumin nano granule, comprise the curcumin nano granule, it is characterized in that, also contains lysozyme, and described lysozyme engages with described curcumin by covalent bond.
2. lysozyme curcumin nano granule as claimed in claim 1, is characterized in that, the particle diameter of described lysozyme curcumin nano granule is 105 ~ 135 nanometers.
3. lysozyme curcumin nano granule as claimed in claim 1, is characterized in that, the envelop rate of described lysozyme curcumin nano granule is 65.78 ~ 76.36%.
4. lysozyme curcumin nano granule as claimed in claim 1, is characterized in that, the content of described curcumin is 2.69 ~ 3.88% of quality.
5. lysozyme curcumin nano granule as claimed in claim 1, is characterized in that, the carrier of described curcumin nano granule is the copolymer of Polyethylene Glycol and polylactic acid.
6. lysozyme curcumin nano granule as claimed in claim 5 is characterized in that described curcumin: Polyethylene Glycol: the quality percentage composition of polylactic acid is than being 1:5 ~ 7:10 ~ 14.
7. lysozyme curcumin nano granule as claimed in claim 1 is characterized in that described curcumin: lysozyme: Polyethylene Glycol: the quality percentage composition of polylactic acid is than being 1:4 ~ 80:5 ~ 7:10 ~ 14.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110343185.2A CN103083244B (en) | 2011-11-03 | 2011-11-03 | Lysozyme curcumin nanoparticle |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110343185.2A CN103083244B (en) | 2011-11-03 | 2011-11-03 | Lysozyme curcumin nanoparticle |
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| CN103083244A true CN103083244A (en) | 2013-05-08 |
| CN103083244B CN103083244B (en) | 2015-05-13 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019232701A1 (en) * | 2018-06-06 | 2019-12-12 | Huang Chih Ching | Curcumin carbon quantum dots and use thereof |
| CN115957153A (en) * | 2022-12-12 | 2023-04-14 | 华南理工大学 | Nano composition with tissue repairing and anti-inflammatory effects and its preparation method and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1861193A (en) * | 2006-01-17 | 2006-11-15 | 四川大学 | Kidney target precursor medicine, said prepn., its preparing method and application |
| CN101698681A (en) * | 2008-10-10 | 2010-04-28 | 暨南大学 | Chimeric polypeptide with dual-targeting function and applications thereof |
-
2011
- 2011-11-03 CN CN201110343185.2A patent/CN103083244B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1861193A (en) * | 2006-01-17 | 2006-11-15 | 四川大学 | Kidney target precursor medicine, said prepn., its preparing method and application |
| CN101698681A (en) * | 2008-10-10 | 2010-04-28 | 暨南大学 | Chimeric polypeptide with dual-targeting function and applications thereof |
Non-Patent Citations (1)
| Title |
|---|
| CARTIERA MS: "Partial correction of cystic fibrosis defects with PLGA nanoparticles", 《MOL PHARM》, vol. 7, no. 1, 28 February 2010 (2010-02-28), pages 86 - 93 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019232701A1 (en) * | 2018-06-06 | 2019-12-12 | Huang Chih Ching | Curcumin carbon quantum dots and use thereof |
| CN115957153A (en) * | 2022-12-12 | 2023-04-14 | 华南理工大学 | Nano composition with tissue repairing and anti-inflammatory effects and its preparation method and application |
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| CN103083244B (en) | 2015-05-13 |
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