EP3843708A2 - Biopolymer based carrier system - Google Patents
Biopolymer based carrier systemInfo
- Publication number
- EP3843708A2 EP3843708A2 EP19868839.2A EP19868839A EP3843708A2 EP 3843708 A2 EP3843708 A2 EP 3843708A2 EP 19868839 A EP19868839 A EP 19868839A EP 3843708 A2 EP3843708 A2 EP 3843708A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- solution
- egg shell
- silk fibroin
- water
- membrane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/04—Making microcapsules or microballoons by physical processes, e.g. drying, spraying
- B01J13/043—Drying and spraying
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
- A23P10/30—Encapsulation of particles, e.g. foodstuff additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/11—Encapsulated compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
- A61K8/982—Reproductive organs; Embryos, Eggs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/987—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of species other than mammals or birds
- A61K8/988—Honey; Royal jelly, Propolis
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/10—General cosmetic use
Definitions
- the invention relates to a double-layer biopolymer-based nano/micro carrier system comprising a core layer made of a natural compound and an egg shell membrane protein and a shell layer of silk fibroin and to optimization of the components of this system by changing some of their physical properties.
- solubility of these valuable compounds may be very low (for example, the solubility of trans resveratrol in water), they may have significantly low bioavailability. These high bioavailability decreases and low stability that are observed make it inevitable to increase the stability by means of encapsulation techniques of these compounds that can have such trans-cis conversions.
- the stability problem of these compounds is frequently mentioned in studies carried out with natural compounds.
- Environmental factors such as heat, light and process conditions cause these compounds to lose their activity or cause a decrease in their efficiency and this stability problem is tried to be solved with various encapsulation methods.
- the encapsulation of bioactive or natural bioactive compounds can be carried out with methods such as; spray drying, liposomes, inclusion encapsulation, co-crystallization, freeze drying, emulsion and nano encapsulation.
- Spray drying method Materials such as anthocionins, procyanidins, grape seed extract, apple polyphenol extract and olive leaf extract can be encapsulated with this method.
- the disadvantage of this method is that the stability of the natural compound is affected by high temperature due to the introduction of the product to be dried into the hot air stream during spray drying in order to evaporate the solution.
- Microemulsion-based systems Lipophilic bioactive compounds can be encapsulated by this method.
- the disadvantage of this method is that it requires a large amount of surfactants. Therefore this is a reason that is economically restrictive.
- a mixture of triglycerides oil phase, lecithin and nonionic surfactant is used as a surfactant.
- Liposome -based systems Trans resveratrol, a polyphenolic natural compound, can be encapsulated in liposome-based systems using soy lecithin and oleic acid. Different materials are used in the encapsulation of trans-resveratrol with liposomes and necessary yield comparisons are made. The most efficient approach is the extrusion method. In this method, small and stable liposomes are produced with high encapsulation yield and good antioxidant activity.
- Freeze-drying method Canberrv extract with anthocyanin and hibiscus sabdarijfa 1. extract can be encapsulated. This method; is quite an expensive method because the drying speed is low and it requires high amounts of energy for the vacuuming process.
- Inclusion method Natural compounds such as hesperetin, hesperidine, resveratrol, oleuropein can be encapsulated with this method.
- Nanoencapsulation method Natural compounds such as resveratrol, elagic acid, curcumin, quercetin, tea catechin, tannin acid, EGCG, theaflavin can be encapsulated.
- the compatibility of the materials used in this method is very important. If materials that are not compatible with each other are selected, the method may be insufficient to provide the stability of the natural compound.
- Emulsion based systems It shows thermodynamically unstable colloidal distribution compared to micro emulsion based systems.
- natural compounds are encapsulated using various oil carriers and emulsifiers.
- peanut oil is widely used because of its high solubility characteristic for natural compounds.
- Biopolymer-based systems The advantage of these systems is that they can be made from natural materials such as proteins and polysaccharides and are easier to work on a laboratory scale. However; some commonly used conventional techniques may have problems regarding scale-ups and adaptation to industry. By using biopolymer based systems, high encapsulation and long retention efficiency was obtained.
- Trans-resveratrol which is a polyphenolic compound, can be encapsulated with chitosan particles by cross-linking with vanillin.
- the present invention is related to a double layer biopolymer based coaxial nano/micro carrier particle system that is obtained by applying the electro-encapsulation method to silk fibroin and egg shell membrane protein that can be obtained having different properties by pre-treatments carried out to increase the efficiency of natural compounds, to provide protection from environmental factors and to increase the stability by decreasing chemical degradability.
- the silk fibroin shell layer allows the controlled release of the natural compound that encapsulated in the core layer.
- biopolymer-based nano/micro carrier particle system and its production method is disclosed.
- the efficiency of natural compounds is increased, protection from environmental factors is provided and chemical stability is reduced and stability is increased.
- the egg shell membrane protein and silk fibroin pair which will be used for the first time in literature are used as a carrier particle system.
- soluble egg shell membrane protein in the core and fully biocompatible silk fibroin in the shell in this system the effects on the natural compound from environmental factors and the stability problem is minimized, and the release profile is controlled.
- particle size distribution is achieved in a narrow space (close to monodisperse) and the method ensures for the encapsulation products to be homogeneous.
- the use of silk fibroin solution and soluble eggshell proteins obtained from the egg shell membrane by using a coaxial nozzle for encapsulation provides cost advantage.
- the biopolymers used in the invention are completely natural and free from substances that may harm human health.
- the electro-encapsulation method used in the invention does not use any heat treatment, which ensures that the stability of the natural compounds is not adversely affected. Additionally, since the soluble eggshell membrane protein is obtained from egg shells which are considered as waste in the industry, it creates value for these wastes by creating an alternative field of application for the egg industry wastes. In this method, unlike other methods, lower bioactive material degradation, obtaining a product in one step, better control of particle size distribution and morphology can be achieved.
- Figure 1 Schematic representation of the electro-encapsulation method.
- FIG. 1 Steps of particle formation by electrospraying method.
- Figure 3 A and B) The nano/micro carrier particle system of the invention.
- FIG. 4 Scanning electron microscopy (SEM) images of the encapsulated trans-resveratrol-containing carrier particle system.
- SEM Scanning electron microscopy
- Figure 5 FT-IR spectra of the obtained particles, silk fibroin, resveratrol and eggshell membrane protein.
- Figure 6 Molecular weight distribution of eggshell protein produced by 3-mercaptopropionic acid treatment as measured by HPLC.
- Figure 7 Molecular weight distribution of eggshell protein produced by Pepsin enzyme treatment as measured by HPLC.
- Figure 8 Molecular weight distribution of silk fibroin solution measured by HPLC.
- Figure 9 Molecular weight distribution of silk fibroin solution concentrated with PEG.
- FIG 10 Atomic force microscopy (AFM) images of the encapsulated trans-resveratrol-containing carrier particle system.
- the image A) measured at AFM of the particles sprayed such that the silk and SEP (Soluble eggshell membrane protein) flow rates are O. lml/h, 20kV, d 6 cm having a SEP (Soluble Eggshell membrane Protein) and trans resveratrol solution in the core section and having a silk fibroin solution at the shell section, and 3D topography B).
- AFM Atomic force microscopy
- Figure 11 Time-dependent release of trans resveratrol from particles.
- Core region comprising a natural compound in the soluble eggshell membrane matrix.
- Spherical nano / micro carrier system formed by an electro-spray method comprising the elements numbered 21 and 22.
- a micro/nano-carrier particle system (23) is produced by means of the electro encapsulation method.
- the micro/nano-carrier particle system ( Figure 3B); comprises a core layer (21) formed of an egg shell membrane protein carrying a natural compound and a shell layer (22) formed of silk fibroin.
- a method of obtaining the biopolymer-based nano/micro carrier particle system of the present invention comprising the process steps of;
- the droplet size depends on the delivery distance and hence the duration, and the particle size obtained is also related to the geometry of the sprayer system.
- the method of obtaining the eggshell protein used to form the interior of the nano/micro carrier particle system (23) subject to the invention comprises the following process steps;
- Method 1 comprises the following process steps
- Method 2 comprises the following process steps;
- the method of obtaining silk fibroin that is used to form the shell portion of the nano/micro carrier particle system of the invention comprises the process steps of;
- the silk fibroin After the sericin is removed from raw silk the remaining is known as the silk fibroin. Rinsing of the resulting silk fibroin with pure water and drying,
- the Ajisawa solution used is prepared as calcium chloride: ethanol: water (CaC12: EtOH: H20) that is 111 : 92: 144 by weight ratio. For 1.2 grams of silk, Ajisawa solution that is 20 times the weight of silk is used.
- nanospheres whose shell portion comprises silk fibroin, which contain eggshell membrane protein and resveratrol that is a natural compound, are obtained between 100-250 nm successfully by means of the invention.
- the particles obtained as a result of the tests carried out, silk fibroin, trans resveratrol and the FT-IR spectra of the soluble eggshell membrane poteins have been illustrated together in Figure 5.
- the characteristic peaks in the spectrum of the nanoparticles have been compared with the characteristic peaks of the materials forming the nanoparticles. It has been observed that the obtained particles carry the characteristic peaks of silk fibroin and eggshell protein and that trans resveratrol is effectively encapsulated.
- the molecular weight distribution of the eggshell membrane protein solution obtained depending on the preferred method for breaking the disulfide bonds varies. In the studies of the invention, both low yield and large molecular weight distribution was measured for the eggshell membrane protein obtained by pepsin enzyme digestion. For the determination of molecular weight, size exclusion high performance liquid chromatography (SEC-HPLC) method was used. The molecular weight distribution of protein solutions prepared according to molecular weight and retention time in the standard protein mixture was determined. When the molecular weight distribution of silk fibroin film solution was calculated, it was observed that the molecular weight distribution started at 23 kDa and ended at 1.5 kDa.
- SEC-HPLC size exclusion high performance liquid chromatography
- Peaks indicating the presence of protein molecules at a molecular weight of 2500 kDa and 0.2 kDa were also observed, but analyzes revealed that 69% of the prepared solution had an average molecular weight of 6.6 kDa.
- the molecular weight distribution of silk fibroin solution prepared with Ajisawa solution and prepared without regeneration was calculated, it was observed that the molecular weight started at 50.6 kDa and ended at 1 kDa. Peaks were also observed at molecular weights of 3500 kDa and 0.2 kDa, but 75% of the prepared solution had an average molecular weight of 0.05 kDa.
- Viscosity is one of the other parameters effective in electro-encapsulation. Since the viscosity of the prepared solution directly influenced the flow through the nozzle, it was used as an encapsulation parameter.
- the silk fibroin solution prepared by the invention is concentrated to observe the effect of viscosity on encapsulation. To prepare samples of different viscosity, the silk fibroin solution was concentrated in a rotary vacuum evaporator. High concentration samples were also prepared using different polymers in silk fibroin dialysis. The viscosity of the prepared samples was measured by a viscosity meter.
- the electrical conductivity of the prepared solutions was determined as one of the most important parameters in the electro-encapsulation.
- the eggshell protein prepared for this purpose was dissolved in both acetic acid and ethanol solution. Since the electrical conductivity was higher in the polymer solution prepared in acetic acid solution, better results were obtained. Electrical conductivity was measured with a conductivity meter.
- the method of preparing eggshell membrane protein involves breaking the disulfide bonds with mercaptopropionic acid solution.
- pepsin digestion and mercaptopropionic acid solution and protein production results are compared, it is seen that higher yield is obtained with mercaptopropionic acid.
- release tests were conducted. Release tests were conducted in phosphate buffer prepared as pH 7 by including a certain amount of prepared particles. Samples were analyzed on the calibration curve prepared by standard trans resveratrol in HPLC. The result of the release kinetics is shown in Figure 11. As can be seen in Figure 11, the amount of trans resveratrol released into the medium increases over time. This indicates that the stability of the trans resveratrol is maintained and that trans resveratrol emits a slow release from the developed carrier system. Release starts after about one hour and continues to increase for 4 hours.
- the subject matter of the invention is a biopolymer based nano/micro carrier particle system that can be used in foods, drugs, feeds, cosmetics, pharmaceuticals, and chemical and biomedical sectors.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Birds (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Nanotechnology (AREA)
- Dispersion Chemistry (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Developmental Biology & Embryology (AREA)
- Reproductive Health (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Dermatology (AREA)
- Peptides Or Proteins (AREA)
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TR201814254 | 2018-10-01 | ||
PCT/TR2019/050810 WO2020072019A2 (en) | 2018-10-01 | 2019-09-30 | Biopolymer based carrier system |
Publications (2)
Publication Number | Publication Date |
---|---|
EP3843708A2 true EP3843708A2 (en) | 2021-07-07 |
EP3843708A4 EP3843708A4 (en) | 2022-02-23 |
Family
ID=70055984
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19868839.2A Pending EP3843708A4 (en) | 2018-10-01 | 2019-09-30 | Biopolymer based carrier system |
Country Status (2)
Country | Link |
---|---|
EP (1) | EP3843708A4 (en) |
WO (1) | WO2020072019A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114295521A (en) * | 2022-01-07 | 2022-04-08 | 四川大学 | Method for measuring surface tension coefficient of liquid by using needle tube |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112691087B (en) * | 2021-01-25 | 2022-02-25 | 潍坊医学院 | Natamycin nanoparticles and preparation method thereof |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105963275B (en) * | 2016-05-31 | 2019-05-17 | 中国医学科学院生物医学工程研究所 | The controllable fibroin albumen micro-capsule of shell and preparation method |
-
2019
- 2019-09-30 WO PCT/TR2019/050810 patent/WO2020072019A2/en unknown
- 2019-09-30 EP EP19868839.2A patent/EP3843708A4/en active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114295521A (en) * | 2022-01-07 | 2022-04-08 | 四川大学 | Method for measuring surface tension coefficient of liquid by using needle tube |
CN114295521B (en) * | 2022-01-07 | 2023-04-25 | 四川大学 | Method for measuring surface tension coefficient of liquid by using needle tube |
Also Published As
Publication number | Publication date |
---|---|
WO2020072019A2 (en) | 2020-04-09 |
WO2020072019A3 (en) | 2020-05-14 |
EP3843708A4 (en) | 2022-02-23 |
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