CN102010513A - Stable polysaccharide modified gelatin nano particle and preparation method and application thereof - Google Patents
Stable polysaccharide modified gelatin nano particle and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a stable polysaccharide modified gelatin nano particle and a preparation method and application thereof, which belong to the field of polymer chemistry, medicinal preparation technology and food chemistry. The nano particle is in an interlinking structure, which takes gelatin as a core and takes polysaccharide as a shell. The preparation method of the nano particle mainly comprises the following steps of: carrying out Maillard reaction on gelatin and polysaccharide, heating and interlinking globular proteins. The nano particle is suitable for being used as the carrier of small molecular substances, i.e. medicines, nutrients, spices, dyes and the like are loaded into the nano particle by using a mixing and dispensing method, so that the nano particle carrying medicines, nutrients, spices, dyes and other substances is obtained.
Description
Technical field
The present invention relates to a kind of stable polyose modification gelatin nanoparticle and its production and application, belong to polymer chemistry, drug preparation technique and food chemistry field.
Background technology
Nanosecond science and technology combine with life medical science, make the mankind obtain new understanding and approach at aspects such as medical diagnosis on disease, treatments, and nanometer medicine-carried system is exactly one of them very vital research direction.A desirable nano-medicament carrier will satisfy many conditions such as good biocompatibility, targeted, sustained release.
Gelatin (gelatin) is the hydrolysate that a class derives from collagen protein in the animal connective tissue, have excellent biological compatibility, biodegradable and do not have immunizing antigen and good viscosity, gelling, film-forming properties etc., be widely used in food, makeup and the medicine industry.The gelatin nanoparticle can be used for adsorbing or various medicines of different nature of embedding (as antitumor drug taxol and Zorubicin etc.) or inorganic particulate (as gold, ferric oxide etc.).
Because gelatin has good gelling, gelatin obtains reversible gel easily under conditions such as certain temperature, concentration, pH, therefore the general preparation method of stable gelatin nanoparticle for glutaraldehyde auxiliary crosslinked two go on foot the method for desolvating.But glutaraldehyde has certain cytotoxicity, and certain limitation is arranged during as the preparation of medical material.
On the other hand, common gelatin nanoparticle does not possess long recursive nature in vivo easily by reticuloendothelial system phagocytic.Through surface hydrophilic modify the gelatin nanoparticle, can obtain long circulation gelatin nanoparticle.At present about the surface hydrophilic of gelatin nanoparticle modify research more be PEG modification method.But bibliographical information PEG modifies gelatin or PEG modification gelatin nanoparticle preparation process is loaded down with trivial details, usually use organic solvent and poisonous chemical reagent, pollute easily, threaten for the medicine securing band, safety requirements in the incompatibility body, { Biomacromolecules 2004,5:202-208}{Journal of PharmaceuticalSciences 96 (2): 397-407.} also to be unfavorable for industrial production.Recently, there is research report to contain wetting ability polysaccharide segmental nanoparticle such as dextran and also has the long recursive nature of similar PEGization nanoparticle in vivo.Discoveries such as Chauvierre can cause the Tisuacryl monomer polymerization at the dextran molecule chain end and obtain dextran-b-paracyanogen base butyl acrylate segmented copolymer, nanoparticle by this class dextran segmented copolymer preparation not only can reduce plasma proteins absorption, but also possesses long recursive nature { Colloid and Polymer Science 282 (9): 1016-1025.}.
Therefore, gelatin nanoparticle that develops a kind of stable polyose modification and its production and application has good application prospects.The present invention intends adopting the crosslinked and Maillard of globular proteins to react preparing a kind of research of stable polyose modification gelatin nanoparticle not appear in the newspapers.
The heating gelatination property of globular proteins can be used for improving food matter structure and local flavor, has obtained a lot of food research workers' attention, has formed more complete theoretical basis.Under certain thermally denature condition, thermally denature can take place globular proteins further assembles the formation cross-linked network structure, usually this crosslinked be irreversible.For globular preteins, when the temperature of solution is elevated to the temperature of protein denaturation when above, the tertiary structure of the globular preteins of native state is suffered destruction to a certain degree, hydrophobic grouping is exposed to the surface of molecule, hydrophobic interaction between the protein molecular is strengthened and assemble, be accompanied by the formation of disulfide linkage, the permutoid reaction of disulfide linkage and the destruction of hydrogen bond at this moment.Intermolecular interaction takes place and forms compound polyelectrolyte in globular proteins and gelatin, and compound polyelectrolyte is further assembled the irreversible cross-linked network structure of formation during heating.
The Maillard reaction is abiogenous reaction between aminocompound in food-processing and the storage (amino acid, polypeptide and protein) and the carbonyl compound (recuding sugars).About the reaction of the Maillard between protein and the polysaccharide existing in the world very mature theory basis and experimental technique, the Maillard reaction is generally carried out under dry heat condition, does not add other chemical reagent, and mild condition is to the human body safety non-toxic.The Maillard reaction of existing bibliographical information gelatin and monose or oligose can improve the gellifying property of gelatin, but up to the present yet there are no the Maillard repercussion study report of gelatin and polysaccharide.By Maillard prepared in reaction gelatin-polysaccharide covalent binding substances, and the research that further prepares polyose modification gelatin nanoparticle does not have the research report yet.
Summary of the invention
One of purpose of the present invention provides a kind of nanoparticle with gelatin nuclear-polysaccharide shell structure.
Two of purpose of the present invention provides a kind of gelatin nanoparticle preparation method of simple, efficient, safe, stable polyose modification.
Three of the object of the invention provides the application method of the gelatin nanoparticle of above-mentioned polyose modification.
A kind of stable polyose modification gelatin nanoparticle is to be that nuclear, polysaccharide are the mono-dispersed nano particle with cross-linked network structure of shell with the gelatin.
Described gelatin is alkaline process gelatin or acid process gelatin, and to be that dextran, polygalactomannan, pulullan polysaccharide, maltodextrin or other are uncharged have the water-soluble polysaccharide of reductibility hydroxyl and their derivative to described polysaccharide; Linking agent in the described cross-linked network structure is that albumin, N,O-Diacetylmuramidase, beta-lactoglobulin, alpha-lactalbumin or other have the globular proteins of heating gelling properties.
A kind of stable polyose modification gelatin nanometer particle process method: comprise that with gelatin, polysaccharide be raw material, utilize Maillard prepared in reaction gelatin-polysaccharide covalent binding substances; Under heating condition, make gelatin-polysaccharide covalent binding substances form nanoparticle then by linking agent.
Described gelatin is alkaline process gelatin or acid process gelatin, and described polysaccharide is dextran, polygalactomannan, pulullan polysaccharide or unchargedly has the water-soluble polysaccharide of reductibility hydroxyl or their derivative; Linking agent in the described cross-linked network structure is albumin, N,O-Diacetylmuramidase or the globular proteins with heating gelling properties.
The molecular weight of described polysaccharide is between 1k～100k.
The quality ratio of described gelatin and polysaccharide is 1: 50-50: 1; Preferred 1: 10-10: between 1.
The Maillard reaction conditions of described formation gelatin-polysaccharide covalent binding substances is:
(1) temperature of reaction is 40～100 ℃; Preferred 60 ℃;
(2) reaction times is 30min～300h; Preferred 24 ℃;
(3) reaction pH is 4～11; Preferred 7;
(4) being reflected at solid phase or liquid phase carries out.
Described crosslinker concentration is 0.01%～10%; The mass ratio of linking agent and gelatin is 1: 10～10: 1.
Described polyose modification gelatin nanoparticle can be used for embedding medicinal, nutritive substance, dyestuff or spices.Its method by direct mixing and adjusting pH is wrapping to medicine, nutritive substance, dyestuff or spices in the nanoparticle.
The present invention is a raw material with gelatin, polysaccharide, the globular preteins of natural origin, not with an organic solvent, prepares the stabilized nano gel by two step reacting by heating.
The first step of the present invention is coupled to polysaccharide covalent on the gelatin by the Maillard reaction, forms gelatin-polysaccharide covalent mixture.The Maillard temperature of reaction is 40～100 ℃ of scopes, and the reaction times, reaction pH was 4～11, is reflected in solid phase or the liquid phase and carries out at 30min～300h.Generally speaking, when being reflected at comparatively high temps and carrying out, required time shortens greatly; When being reflected at higher pH and carrying out, required time shortens greatly.The Maillard reaction conditions of optimizing reduces preparation cost, and Maillard reaction of the present invention is usually at 60 ℃, and reaction pH is 7, and the reaction times is to carry out under the 24h.The gentle easily control of above-mentioned reaction conditions, reaction product does not generally show tangible browning reaction, good water solubility.
In addition, by the feed ratio and the polysaccharide chain length of control polysaccharide, gelatin, can regulate the content of polysaccharide in the protein-polysaccharide covalent mixture.The molar ratio of gelatin and polysaccharide is between 1: 50 to 50: 1, and between preferred 1: 10 to 10: 1, polysaccharide molecular weight can form nanoparticle at 1k to protein-polysaccharide covalent mixture prepared between the 100k.Maillard reaction product of the present invention does not need further separation, can directly carry out next step reaction.
Second step of the present invention, after the Maillard reaction product that the first step is prepared is dissolved in water, add globular proteins solution then as linking agent, the pH value of regulating mixing solutions is to certain limit, there are Intermolecular Forces in gelatin and globular preteins and tend to mutual gathering, and heat mixing solutions this moment.Abundant sex change takes place in protein under heating condition, generates the cross-linked network structure that is formed by intermolecular hydrophobic aggregation, hydrogen bond and disulfide linkage, can obtain having the nanoparticle of cross-linked network structure.It is that nuclear (main component is a gelatin), polysaccharide are the structure of shell that this nanoparticle has with protein, and promptly protein molecule mainly is positioned at the inside of nanoparticle, and hydrophilic polysaccharide is positioned at the outside of nanoparticle, plays a part stable interface.
Among the present invention, polysaccharide is the water-soluble polysaccharide that contains the reductibility terminal hydroxy group, can be straight chain type polysaccharide and branched chain type polysaccharide, for example dextran and polygalactomannan.Cross-linked proteins is a globular protein matter, and possesses by heating the character that its aqueous solution can form macroscopical irreversible gel, as albumin, N,O-Diacetylmuramidase etc.In the reaction of second step, the choice criteria of Heating temperature and heat-up time is the fully sex change of protein that makes in the solution; PH value during heating is controlled within isoelectric point of protein ± 3 scopes can obtain the stabilized nano gel; The size that can regulate nanogel by control pH value of solution value and protein concn changes between 50～1000nm.
The nanoparticle that utilizes the present invention to obtain has good monodispersity, measures hydromeehanics diameter between 50～1000nm (Fig. 1) greatly with dynamic light scattering.Prepared nanoparticle can also be preserved through obtaining powder after the lyophilize in the medium-term and long-term preservation of the aqueous solution, and this powder can be distributed in the aqueous solution again and keep original particle diameter and size distribution (Fig. 1).After prepared nanoparticle was deposited in the aqueous solution 120 days, its size distribution did not almost change.Obtain the nanoparticle of ganoid almost spherical by atomic force microscope observation, particle size range is at 50～500nm (Fig. 2).
Utilizing the inventive method can obtain gelatin concentration is 10% or the higher nanoparticle aqueous solution, and nanoparticle productive rate height, product do not need to separate, and can directly carry out next step carrying medicament etc.
Contain various hydrophobic and charge residue residue in the gelatin chains, can there be non-covalent interaction power with multiple medicine, can the electrically charged and hydrophobic small-molecule substance of load such as medicine, nutritive substance, dyestuff, spices etc. by control solution condition (such as pH value of solution value, temperature, ionic strength); Can also or in the process that forms gel, small molecules be loaded in the nanoparticle by the dialysis diffusion by direct blended method.The drug prepared carrier is fit to multiple route of administration, as injection, mucous membrane, oral administration.
In the inventive method, compare with technology in the past, the present invention has prepared a kind of gelatin nanoparticle of stable polyose modification, this nanoparticle raw material sources are extensive, whole process of preparation all meets the Green Chemistry condition, avoids using harmful chemical reagent, such as glutaraldehyde etc., have higher security, preparation is simple.Hydrophilic dextran can improve the pH stability of gelatin nanoparticle and the stability of solution under the physiological ionic strength, gives the long recursive nature of gelatin nanoparticle as pharmaceutical carrier.
Description of drawings
Fig. 1 is the size distribution figure before and after gelatin of the present invention-dextran nanoparticle freeze-drying.
Fig. 2 is the atomic force microscope figure of gelatin of the present invention-dextran nanoparticle.
Embodiment
Following examples are intended to illustrate the present invention rather than limitation of the invention further.
Embodiment 1.
Glucan-modified alkaline process gelatin nanoparticle
Glucan-modified alkaline process gelatin nanometer particle process method be divided into two the step carry out.The first step is dissolved in alkaline process gelatin in the deionized water, is made into 20mgmL
-1Alkaline process gelatin solution.The mixing solutions of the dextran that adds molecular weight and be 62k preparation polysaccharide and alkaline process gelatin in the above-mentioned solution, and make alkaline process gelatin: dextran is 1: 1 (mass ratio), mixes solution, the pH value of solution is adjusted to 8, then with the mixing solutions lyophilize.Cryodesiccated solid is placed on (relative humidity is 79%) in the encloses container that the KBr saturated solution is housed, places and carry out Maillard reaction 24h under 60 ℃.With Maillard reaction product deionized water dissolving, be made into alkaline process gelatin-dextran covalent complex solution, make that alkaline process gelatin concentration is 20mgmL in the covalent complex
-1Second step added a certain amount of N,O-Diacetylmuramidase in alkaline process gelatin-dextran covalent complex solution, add certain water gaging again, made alkaline process gelatin concentration, lysozyme concentration be 1.0mgmL
-1Use 0.1molL then
-1The pH value to 10 of NaOH solution regulator solution about, again solution is placed 80 ℃ water-bath to heat 0.5h, can obtain after the cooling heterogeneity index about 0.10, particle diameter is 200nm stabilized nano particle.Fig. 1 obtains the size distribution figure of nanoparticle for the dynamic laser light scattering measurement: mean hydrodynamic diameter is 200nm, and heterogeneity index is 0.10.This nano-particle solution stability is high, deposits in 4 ℃ refrigerator and does not have the generation of precipitation clustering phenomena in 3 months.With above-mentioned nano-particle solution lyophilize, with the dissolving again in deionized water of resulting pressed powder, can obtain the stabilized nano particle solution then, size distribution changes little (Fig. 1).
Carrying out heat cross-linking under different lysozyme concentration, to prepare the light-scattering analysis result of glucan-modified alkaline process gelatin nanoparticle as shown in table 1, all can obtain the nanoparticle of particle diameter below 200nm.
Table 1
Selecting bovine serum albumin for use is the protein cross agent, and (dextran molecule amount 62k, alkaline process gelatin: dextran is 1: 1 (mass ratio) to the glucan-modified alkaline process gelatin nanoparticle for preparing, and alkaline process gelatin and bovine serum albumin concentration are 1.0mgmL
-1The heat cross-linking temperature is 80 ℃, and pH is 6.0, and the time is 1h) also can obtain the stabilized nano particle solution.With the resulting nano-particle solution of dynamic laser light scattering measurement: particle diameter is 110nm, and heterogeneity index is 0.14.
Embodiment 2.
Glucan-modified acid process gelatin nanoparticle
Acid process gelatin and dextran are carried out the synthetic acid process gelatin of Maillard reaction-dextran covalent complex, and the Maillard reaction conditions is with embodiment 1.Glucan-modified acid process gelatin nanometer particle process method be divided into two the step carry out.The first step, preparation 20mgmL
-1The acid process gelatin aqueous solution.Adding molecular weight respectively is 10k, 35k, the dextran of 62k is prepared the polysaccharide of different molecular weight and the mixing solutions of acid process gelatin in above-mentioned solution, and make acid process gelatin: dextran is 1: 4～4: 1 (mass ratio), mix solution, the pH value of solution is adjusted to 8, then with the mixing solutions lyophilize.Cryodesiccated solid is placed on (relative humidity is 79%) in the encloses container that the KBr saturated solution is housed, places and carry out Maillard reaction 24h under 60 ℃.With Maillard reaction product deionized water dissolving, be made into acid process gelatin-dextran covalent complex solution, make that acid process gelatin concentration is 20mgmL in the covalent complex
-1Second step added a certain amount of N,O-Diacetylmuramidase in acid process gelatin-dextran covalent complex solution, add certain water gaging again, made acid process gelatin concentration, lysozyme concentration be 1.0mgmL
-1Use 0.1molL then
-1The pH value to 10 of NaOH solution regulator solution about, again solution is placed 80 ℃ water-bath to heat 0.5h, can obtain stable glucan-modified acid process gelatin nanoparticle after the cooling.
Prepare the light-scattering analysis result of glucan-modified acid process gelatin nanoparticle under condition of different pH, concrete outcome is as shown in table 2, the heterogeneity index of nanoparticle about 0.2, particle diameter is in the scope of 100～300nm.The quality feed ratio WR (gelatin/dextran) of the dextran of employing different molecular weight and different dextran and acid process gelatin is at the resulting nanoparticle of above-mentioned condition, concrete outcome is as shown in table 3, the heterogeneity index of nanoparticle about 0.3, particle diameter is 100～200nm.
Table 2 prepares the light-scattering analysis result of glucan-modified acid process gelatin nanoparticle under condition of different pH (dextran molecule amount 62k, acid process gelatin: dextran is 1: 1 (mass ratio), and the concentration of acid process gelatin is 1.0mgmL
-1, the concentration of N,O-Diacetylmuramidase is 1.0mgmL
-1).
Table 2
The quality feed ratio WR (gelatin/dextran) of the dextran of table 3 different molecular weight and different dextran and acid process gelatin is in the light-scattering analysis result of the resulting nanoparticle of above-mentioned condition.
Table 3
Embodiment 3.
Polygalactomannan is modified the acid process gelatin nanoparticle
Acid process gelatin and polygalactomannan carry out the Maillard reaction and generate acid process gelatin-polygalactomannan covalent complex, and the Maillard reaction conditions is with embodiment 1.With Maillard reaction product deionized water dissolving, obtaining acid process gelatin concentration is 1.0mgmL
-1Solution is used 0.1molL
-1NaOH regulates the pH value to 10.0 of above-mentioned solution, then solution is placed 80 ℃ water-bath to heat 1h, can obtain the stabilized nano particle solution.With the resulting nano-particle solution of dynamic laser light scattering measurement: median size is 330nm, and heterogeneity index is 0.26.
Embodiment 4.
Polygalactomannan is modified the alkaline process gelatin nanoparticle
Alkaline process gelatin and polygalactomannan carry out the Maillard reaction and generate alkaline process gelatin-polygalactomannan covalent complex, and the Maillard reaction conditions is with embodiment 1.With Maillard reaction product deionized water dissolving, obtaining alkaline process gelatin concentration is 1.0mgmL
-1Solution is used 0.1molL
-1NaOH regulates the pH value to 10.0 of above-mentioned solution, then solution is placed 80 ℃ water-bath to heat 1h, can obtain the stabilized nano particle solution.With the resulting nano-particle solution of dynamic laser light scattering measurement: median size is 188nm, and heterogeneity index is 0.11.
Embodiment 5.
Pulullan polysaccharide is modified the alkaline process gelatin nanoparticle
Alkaline process gelatin and pulullan polysaccharide carry out the Maillard reaction and generate alkaline process gelatin-pulullan polysaccharide covalent complex, and the Maillard reaction conditions is with embodiment 1.With Maillard reaction product deionized water dissolving, obtaining alkaline process gelatin concentration is 1.0mgmL
-1Solution is used 0.1molL
-1NaOH regulates the pH value to 10.0 of above-mentioned solution, then solution is placed 80 ℃ water-bath to heat 1h, can obtain the stabilized nano particle solution.With the resulting nano-particle solution of dynamic laser light scattering measurement: median size is 216nm, and heterogeneity index is 0.08.
Embodiment 6.
Polyose modification gelatin nanoparticle is to the load of multiple materials such as Ibuprofen BP/EP
Polyose modification gelatin nanoparticle preparation method is with embodiment 2.The Ibuprofen BP/EP aqueous solution directly is added drop-wise in the polyose modification gelatin nano-particle solution, slowly regulate the pH value then to certain value, stirring is spent the night, remove not by the guest species of embedding or absorption by centrifugal or filtering method, promptly obtain carrying the polyose modification gelatin nano-particle solution of Ibuprofen BP/EP, last freeze-drying is preserved.Employing is sealed other various materials with the method that above-mentioned bag carries Ibuprofen BP/EP, and concrete outcome is as shown in table 4, and nanoparticle can be realized load to multiple material, and encapsulation rate can reach more than 85%.
Table 4 polyose modification gelatin nanoparticle is to the load of multiple materials such as Ibuprofen BP/EP
Claims (10)
1. a stable polyose modification gelatin nanoparticle is characterized in that, it is to be that nuclear, polysaccharide are the mono-dispersed nano particle with cross-linked network structure of shell with the gelatin.
2. polyose modification gelatin nanoparticle according to claim 1, it is characterized in that, described gelatin is alkaline process gelatin or acid process gelatin, and described polysaccharide is dextran, polygalactomannan, pulullan polysaccharide or unchargedly has the water-soluble polysaccharide of reductibility hydroxyl or their derivative; Linking agent in the described cross-linked network structure is albumin, N,O-Diacetylmuramidase or the globular proteins with heating gelling properties.
3. a stable polyose modification gelatin nanometer particle process method is characterized in that: comprise that with gelatin, polysaccharide be raw material, utilize Maillard prepared in reaction gelatin-polysaccharide covalent binding substances; Under heating condition, make gelatin-polysaccharide covalent binding substances form nanoparticle then by linking agent.
4. preparation method according to claim 3, it is characterized in that: described gelatin is alkaline process gelatin or acid process gelatin, and described polysaccharide is dextran, polygalactomannan, pulullan polysaccharide or unchargedly has the water-soluble polysaccharide of reductibility hydroxyl or their derivative; Linking agent in the described cross-linked network structure is albumin, N,O-Diacetylmuramidase or the globular proteins with heating gelling properties.
5. according to claim 3 or 4 described preparation methods, it is characterized in that the molecular weight of described polysaccharide is between 1k～100k; The quality ratio of described gelatin and polysaccharide is 1: 50-50: between 1.
6. preparation method according to claim 5 is characterized in that, the quality ratio of described gelatin and polysaccharide is 1: 10-10: between 1.
7. preparation method according to claim 6 is characterized in that: the Maillard reaction conditions of described formation gelatin-polysaccharide covalent binding substances is:
(1) temperature of reaction is 40～100 ℃;
(2) reaction times is 3min～300h;
(3) reaction pH is 4～11;
(4) being reflected at solid phase or liquid phase carries out.
8. preparation method according to claim 7 is characterized in that: the Maillard reaction conditions of described formation gelatin-polysaccharide covalent binding substances is:
(1) temperature of reaction is 60 ℃;
(2) reaction times is 24h;
(3) reaction pH is 7;
(4) being reflected at solid phase or liquid phase carries out.
9. according to claim 3 or 4 described preparation methods, it is characterized in that: described linking agent mass concentration is 0.01%～10%; The mass ratio of linking agent and gelatin is 1: 10～10: 1.
10. claim 1 or 2 described polyose modification gelatin nanoparticles can be used for embedding medicinal, nutritive substance, dyestuff or spices.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102924929A (en) * | 2012-10-03 | 2013-02-13 | 中南大学 | Nanoparticles for encapsulating polyphenol active substances and preparation method thereof |
| CN104356406A (en) * | 2014-10-31 | 2015-02-18 | 中南大学 | Method for coating polyphenol material with gelatin-polysaccharide graft |
| US10568839B2 (en) | 2011-01-11 | 2020-02-25 | Capsugel Belgium Nv | Hard capsules |
| US11319566B2 (en) | 2017-04-14 | 2022-05-03 | Capsugel Belgium Nv | Process for making pullulan |
| US11576870B2 (en) | 2017-04-14 | 2023-02-14 | Capsugel Belgium Nv | Pullulan capsules |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1296852A (en) * | 2000-12-12 | 2001-05-30 | 天津大学 | Chitosan/gelatin network modification on surface of aliphatic polyester |
| US20090004278A1 (en) * | 2006-01-30 | 2009-01-01 | Fujifilm Corporation | Enzymatically Crosslinked Protein Nanoparticles |
| CN101801332A (en) * | 2007-09-20 | 2010-08-11 | 富士胶片株式会社 | Adhesive gel sheet for living organisms and sheet form cosmetics comprising the same |
-
2010
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1296852A (en) * | 2000-12-12 | 2001-05-30 | 天津大学 | Chitosan/gelatin network modification on surface of aliphatic polyester |
| US20090004278A1 (en) * | 2006-01-30 | 2009-01-01 | Fujifilm Corporation | Enzymatically Crosslinked Protein Nanoparticles |
| CN101801332A (en) * | 2007-09-20 | 2010-08-11 | 富士胶片株式会社 | Adhesive gel sheet for living organisms and sheet form cosmetics comprising the same |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10568839B2 (en) | 2011-01-11 | 2020-02-25 | Capsugel Belgium Nv | Hard capsules |
| CN102924929A (en) * | 2012-10-03 | 2013-02-13 | 中南大学 | Nanoparticles for encapsulating polyphenol active substances and preparation method thereof |
| CN104356406A (en) * | 2014-10-31 | 2015-02-18 | 中南大学 | Method for coating polyphenol material with gelatin-polysaccharide graft |
| CN104356406B (en) * | 2014-10-31 | 2017-05-10 | 中南大学 | Method for coating polyphenol material with gelatin-polysaccharide graft |
| US11319566B2 (en) | 2017-04-14 | 2022-05-03 | Capsugel Belgium Nv | Process for making pullulan |
| US11576870B2 (en) | 2017-04-14 | 2023-02-14 | Capsugel Belgium Nv | Pullulan capsules |
| US11878079B2 (en) | 2017-04-14 | 2024-01-23 | Capsugel Belgium Nv | Pullulan capsules |
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