WO2021007635A1 - Procédé d'obtention d'une composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline, composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline et utilisation dans le traitement de plaies - Google Patents

Procédé d'obtention d'une composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline, composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline et utilisation dans le traitement de plaies Download PDF

Info

Publication number
WO2021007635A1
WO2021007635A1 PCT/BR2020/050256 BR2020050256W WO2021007635A1 WO 2021007635 A1 WO2021007635 A1 WO 2021007635A1 BR 2020050256 W BR2020050256 W BR 2020050256W WO 2021007635 A1 WO2021007635 A1 WO 2021007635A1
Authority
WO
WIPO (PCT)
Prior art keywords
chitosan
bromelain
nanoparticles
composition
maltose
Prior art date
Application number
PCT/BR2020/050256
Other languages
English (en)
Portuguese (pt)
Inventor
Janaína Artem ATAÍDE
Danilo Costa GERALDES
Laura de Oliveira NASCIMENTO
Priscila Gava MAZZOLA
Original Assignee
Universidade Estadual De Campinas
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Universidade Estadual De Campinas filed Critical Universidade Estadual De Campinas
Publication of WO2021007635A1 publication Critical patent/WO2021007635A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

Definitions

  • the present invention relates to a process for obtaining a lyophilized composition of chitosan-based nanoparticles containing bromelain.
  • composition proved to be stable in relation to the enzymatic activity using sugars as lyoprotectants.
  • the referred composition does not contain organic solvents or chemical additives, as preservatives, being obtained by green process and based on natural and biocompatible excipients.
  • the present invention reveals its use in the preparation of a medicament to treat wounds.
  • Bromelain a complex of substances extracted mainly from pineapple (Ananas comosus L.) r is recognized for its anti-inflammatory, antithrombotic, fibrinolytic properties, antitumor activity and immunomodulatory effect. Based on Seligman's study that showed, in 1962, its action as an anti-inflammatory agent, several studies support the use of bromelain extracts in different conditions (Seligman, 1962; Taussig and Batkin, 1988;
  • bromelain acts by hydrolyzing devitalized tissue, both in vivo and in vitro, which increases the healing capacity.
  • Wounds are formed from the disruption of the integrity of the skin, mucous surfaces or organ tissues (Young and McNaught, 2011), and although skin lesions vary, they have a common mechanism for repair and healing. Wound healing is a regular biological process in the human body, since human skin has a natural ability to promote self-regeneration after damage (Guo and DiPietro, 2010; Pereira and Bártolo, 2016), and when triggered by a injury, this mechanism comprises an elaborate cascade of physiological events designed to finally heal the skin (Strondtbeck, 2001).
  • the first stage hemostasis, occurs immediately at the time of the injury and usually lasts a few hours.
  • the second stage inflammation, begins shortly after hemostasis and is usually completed within the first 24 to 72 hours after the injury; however, it can last up to 5-7 days after injury (Haas, 1995).
  • Proliferation and repair the third stage, typically occurs 1 to 3 weeks after injury.
  • the fourth and final stage, remodeling begins approximately 3 weeks after the injury and can take months to several years to reach physiological completion.
  • Winter concluded that hydrated wounds in piglets epithelize the skin twice as fast as wounds exposed to air (Winter, 1962).
  • Bioactive or biological dressings are also modern dressings and are produced from biomaterials, which play an important role in the healing process (Boateng et al., 2008; Dhivya et al., 2015). These dressings are known for their biocompatibility, biodegradability and non-toxic nature (Dhivya et al.,
  • bioactive dressings can be incorporated with active compounds, such as antimicrobials and growth factors, improving the healing process (Boateng et al., 2008; Dhivya et al., 2015).
  • bromelain Due to the characteristics exposed above, bromelain has potential applications in the cosmetic, pharmaceutical and food industries. However, the use of proteins as an active ingredient in pharmaceutical products is a challenge, due to its physical and chemical instability.
  • chitosan Due to its characteristics of adhesiveness, biocompatibility, biodegradability and low toxicity, chitosan is an attractive material for several uses, mainly in the pharmaceutical area.
  • This polysaccharide is used in modified drug delivery systems of various therapeutic classes, such as antibiotics, anti-inflammatories, antihypertensives, in addition to peptides and proteins (Bernkop-Schniirch, 2000; Flórea et al., 2006; Boonyo et al. ., 2007; Sandri et al., 2010).
  • the ease of adherence of chitosan, as well as its antifungal, bacteriostatic character and its permeability to oxygen are very attractive properties for topical use (Arguelles, 2004; Jayakumar et al., 2011).
  • the lyophilization process provides solid compositions without heating above room temperature, which provides the stability of the proteins present.
  • the solid state of low humidity prevents or decreases possible chemical, biological reactions and mechanical stress, which can result in stable compositions over the period of months to years without loss of the desired performance.
  • the present invention therefore aimed to encapsulate bromelain in chitosan nanoparticles and lyophilize the composition in order to increase enzymatic stability, in order to produce a drug to treat wounds.
  • Some state-of-the-art documents refer to natural assets for wound care. These assets known in the literature are propolis, Centella asiatica, P ⁇ nica granatum L, Rosmarinus officinalis L and Calendula officinalis, among others. Bromelain, whose properties also make it ideal for wound care, is extensively revised, Ataide et al. Natural actives for wound healing: a review. Phytotherapy Research, 2018.
  • Ekambaram et al. (2017) describes a multi-phase combined distribution system produced by coaxial electrospinning of different biocompatible polymers, with optimization of the ratio and specificity of the polymers for the specific function, using bromelain as a debridement and salviolic acid B as a stimulator of angiogenesis and reepithelization.
  • the in vitro release profile illustrated the sustained release of debridement protease and bioactive component in a timely manner.
  • the manufactured product showed angiogenic potential through the migration of endothelial cells in vitro and an increase in new capillaries from the existing blood vessel in response to a chicken in ovo chorioallantoic membrane assay. With the projected fiber, accelerated wound healing in vivo was also achieved in the full-thickness rat skin wound model.
  • the present invention addresses the problem of the stability of bromelain by proposing a composition in which the chitosan-bromelain nanoparticles are dried by lyophilization in the presence of lyoprotectant composition.
  • the present invention does not deal with chemically modified chitosan, which reduces the excipient cost and maintains the natural appeal of the composition.
  • CN 107475226 discloses a bromelain complex with a polyanionic polysaccharide (alginate, pectin, CMC, gum arabic or xanthan gum), and a polysaccharide or mixture may be used.
  • a polyanionic polysaccharide alginate, pectin, CMC, gum arabic or xanthan gum
  • the inventors complex bromelain with an anionic polysaccharide, thereby increasing its stability.
  • the drying process of the complex, its average size and characteristics is not detailed.
  • the present invention makes use of a polycationic polysaccharide (chitosan has a positive charge), in addition to forming and characterizing nanoparticles with bromelain.
  • CN 1834239 proposes a method for obtaining lyophilized bromelain powders.
  • the enzyme is extracted from the pineapple in stages that involve filtering the juice fruit, adsorption with zinc oxide, ultrafiltration and lyophilization.
  • the innovation is related to the purification method achieved by using zinc oxide, and is intended for application in possible oral compositions.
  • data on stability, storage and conditions under which lyophilization is carried out are not disclosed, although these impact the enzyme activity of the product.
  • the product consists of a pharmaceutical composition of bromelain encapsulated in chitosan, presented as dry powder (lyophilized), stable at room temperature for more than 90 days in relation to particle size and enzymatic activity.
  • Document RU 2677232 refers to a pharmaceutical composition of bromelain encapsulated in low and / or high molecular weight chitosan gel, in the form of macroparticles.
  • the bromelain is immobilized in 50 mM Tris-glycine buffer solution and pH 8, 5-9.0, incubated and the resulting precipitate is washed with 50 mM Tris-HCl buffer and pH 7.5.
  • the invention is intended for the treatment of wounds, providing macroscopic particles of varying sizes. However, it does not present data about the physicochemical characterization of the particles or even about the stability of the composition or the lyophilization conditions.
  • composition has a final pH between 8.5 and 9.0, unsuitable for use on the skin, pH 5.5.
  • the present invention differs in that it is a reproducible composition of lyophilized low molecular weight chitosan nanoparticles. Data on the stability of the composition, as well as the characterization of the nanoparticles, are provided and it has a pH compatible with that of the skin.
  • the present invention relates to a process for obtaining a lyophilized composition of chitosan-based nanoparticles containing bromelain.
  • composition proved to be stable in relation to the enzymatic activity using sugars as lyoprotectants.
  • the present invention reveals its use in the preparation of a medicine to treat wounds.
  • composition obtained in the form of lyophilized powder of nanostructured bromelain can be used as a final pharmaceutical form or as an active pharmaceutical ingredient incorporated in another product.
  • Figure 1 Scanning (A) and transmission (B) electron microscopy of chitosan-bromelain nanoparticles.
  • FIG. 1 Infrared spectra by Fourier transform (FTIR) of bromelain (black), chitosan nanoparticles (red) and chitosan-bromelain nanoparticles (green).
  • FTIR Fourier transform
  • Figure 7 Graphs of the main effect of factorial design relating the variables (inputs) studied in relation to the responses of mean particle size (A), polydispersity index (B), D 10 (C), D 50 (D), D 90 (D), zeta potential (F) and encapsulation efficiency in terms of proteins (G) and enzyme activity (H).
  • FIG. 8 Scanning electron microscopy of lyophilized powder with glycine (A), maltose (B) and after reconstitution with glycine (C) and maltose (D).
  • the present invention relates to the process of obtaining a lyophilized composition based on chitosan nanoparticles containing bromelain.
  • the present invention reveals its use in the preparation of a medicament to treat wounds.
  • composition obtained in the form of lyophilized nanostructured bromelain powder can be used as a final pharmaceutical form or as an active pharmaceutical ingredient incorporated in another product
  • step (b) Add a solution of bromelain at a concentration of 10mg / mL with stirring the solution obtained in step (a) until complete homogenization;
  • step (d) The mixture of the nanoparticles with the lyoprotectant obtained in step (d) stored in an ultrafreezer at -80 ° C;
  • step (e) The nanoparticles frozen at -80 ° C, obtained in step (e) were inserted into the lyophilizer with the shelf set at -45 ° C and maintained until reaching the same temperature as the shelf;
  • step (f) The nanoparticles of step (f) follow the drying ramp, increasing the temperature by 5 ° C from -45 ° C to +10 ° C;
  • the lyoprotectant is selected from small molecules, such as sugars or amino acids, maltose, glycine, preferably maltose.
  • step (g) the temperature is changed when the temperature of the composition reaches the temperature of the shelf, only advancing to the next step when the temperature of the formulation reaches the temperature of the shelf.
  • the nanoparticles obtained in step (c) of chitosan-bromelain have an average diameter of 84.5 to 100.9 nm, a polydispersity index of 0.18 to 0.23, a zeta potential of 21.9 to 27 , 1 mV and a particle concentration in the order of 1012 particles / mL. Still in step c, bromelain is encapsulated in chitosan nanoparticles and has an encapsulation efficiency of 83.4 to 97.8% of the protein concentration, which corresponds to an encapsulation efficiency of 75.5 to 81.6% enzyme activity.
  • the lyoprotectant in step (d) is in a concentration of 3% (m / v) in relation to the volume of the chitosan-bromelain nanoparticle solution.
  • the composition has a collapse temperature ranging from -56 ° C to - 28 ° C, preferably above -40 ° C, with the addition of maltose and glycine, respectively.
  • a lyophilized composition of chitosan-based nanoparticles containing lyophilized bromelain still obtained by the process as defined above and which comprises 0.9% to 1.0% bromelain, 0.9% to 1, 0% chitosan, 3% lyoprotectant.
  • the said composition comprises a lyoprotectant selected from small molecules, which may be sugars or amino acids such as maltose or glycine, preferably maltose.
  • composition object of the present invention comprises nanoparticles with an average diameter of 88.5 and 127.8 nm, a polydispersity index of 0.29 to 0.34, a zeta potential of 20.0 to 23.2 mV .
  • composition obtained by the process is in the form of lyophilized powder, has a maltose encapsulation efficiency of 96.3% to 98.8%, which is equivalent to an enzymatic activity of 73.3 to 99.5%.
  • stage Production of chitosan-bromelain nanoparticles
  • the chitosan solution was prepared in the following proportion 2.5 mg / mL of chitosan in 1% acetic acid, pH 5.0, and subsequently filtered through 0.45um membranes.
  • the TPP solution was prepared in the following proportion 0.5 mg / mL in ultrapure water, then filtered through a 0.22 ⁇ m membrane.
  • the TPP solution is 30% (w / w) in relation to the total amount of chitosan.
  • the nanoparticles were produced by the ionic crosslinking technique (Shu and Zhu, 2000), using sodium tripolyphosphate (TPP) as a crosslinking agent.
  • TPP sodium tripolyphosphate
  • a proportion of 30% (w / w) of TPP was used in relation to the total amount of chitosan, and agitation of 350 rpm.
  • the bromelain solution (10 mg / mL in water) was added under stirring at 350 rpm for 40 minutes, after dripping the TPP solution into the chitosan solution.
  • 1 ml of the bromelain solution was added to produce the bromelain-chitosan nanoparticles or 1 ml of distilled water to produce chitosan nanoparticles.
  • Nanoparticles with and without bromelain produced with different types of chitosan were physically characterized by DLS, zeta potential and NTA.
  • the average diameter and polydispersity index (PDI) of the nanoparticles were evaluated using the Zetasizer Nano ZS equipment (Malvern, United Kingdom). The average size and polydispersity index were determined by dynamic light scattering (DLS), while the zeta potential was measured by Doppler laser microelectrophoresis (Zetasizer Nano ZS, Malvern, United Kingdom).
  • the nanoparticles were ultracentrifuged (Centrifuge 5810R, Eppendorf, Germany) at 4,000g for 10 minutes, using 0.5 mL ultrafiltration devices with 100 kDa membrane (Amicon® Ultra 100k, Millipore, Germany) thus separating the bromelain that remained free from the encapsulated one.
  • Total protein concentration and enzyme activity were determined in the initial bromelain solution and in the filtrate (resulting from the described filtration), and the efficiency was calculated according to equation 1:
  • the initial bromelain solution showed 2.0 ⁇ 0.3 mg / mL of total protein and 23.3 ⁇ 1.6 U / mL. Protein concentration and enzyme activity were also determined in the resulting filtered solution (0.25 ⁇ 0.01 mg / mL and 4.5 ⁇ 0.6 U / mL, respectively) to calculate the encapsulation efficiency, which was 87.0 ⁇ 5.1% of the total protein, corresponding to 80.7 ⁇ 1.1% of the enzymatic activity of bromelain (Table 2).
  • chitosan-bromelain nanoparticles are unstable when stored in liquid form, and therefore lyophilization is an important process to increase the preservation of particle size for long-term storage (Fonte et al., 2016; Almalik et al., 2017) and the enzymatic activity of bromelain (Arakawa et al., 2001).
  • Step 2 Freeze-drying of the nanoparticles of bromelain quitosana-
  • Trealose, maltose and glycine were chosen as possible lyoprotectants, due to their collapse temperatures when alone in solution, with the collapse temperature being -24.3 °, -25.1 and -12.7 ° , respectively. Subsequently, they were dissolved in the suspension of chitosan-bromelain nanoparticles at a concentration of 3% (m / v), to evaluate their effect on the collapse temperature of the suspensions of chitosan-bromelain nanoparticles.
  • the collapse temperature of chitosan-bromelain nanoparticles with and without lyoprotectants was determined by a microscope attached to a lyophilization module, Lyostat 2, model FDCS 196 (Linkam Instruments, Surrey, United Kingdom), equipped with a liquid nitrogen freezing system (LNP94 / 2) and programmable temperature controller (TMS94, Linkam).
  • the chitosan-bromelain nanoparticles showed a collapse temperature of -56 ° C, which decreased to -49.3 ° C, -34.8 ° C and -28.0 ° C with the addition of trehalose, maltose and glycine, respectively .
  • Table 3 Collapse temperature of possible lyoprotectants in isolated solution and in nanoparticles.
  • the lyophilizates were reconstituted in distilled water to analyze the physical characteristics of the particles by dynamic light scattering (Table 4) and the encapsulation efficiency (Figure 5), which were considered outputs for factorial design.
  • Table 4 After lyophilization, glycine in a concentration of 3% (m / v) was able to keep the polydispersity index within the desirable values, however the zeta potential declined. On the other hand, maltose showed the opposite behavior, increasing the polydispersity index and showing little effect on the zeta potential.
  • Table 4 Size of nanoparticles, PDI and zeta potential before and after the lyophilization process (experimental design). The results are presented as mean ⁇ standard deviation of two compositions, measured three times each.
  • Z-ave mean particle size
  • PDI polydispersity index
  • control nanoparticle without lioprotector.
  • compositions containing 3% (w / v) of glycine and maltose as lyoprotectants were the most promising for stabilizing chitosan-bromelain nanoparticles.
  • a new batch of samples with these excipients was produced and lyophilized following the parameters previously determined.
  • the samples were characterized and submitted to a stability study. For this study, the dried samples were kept sealed in the lyophilization vials with plastic wrap and stored at room temperature (25 ° ⁇ 2 ° ) and refrigerator (5 ⁇ 2 o) protected from light.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Dermatology (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Nanotechnology (AREA)
  • Optics & Photonics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un procédé d'obtention d'une composition lyophilisée de nanoparticules de chitosane contenant de la broméline. Ladite composition s'est révélée stable par rapport à l'activité enzymatique utilisant de petites molécules, notamment des sucres ou des acides aminés comme lyoprotecteurs. En outre, la présente invention concerne son utilisation dans la préparation d'un médicament pour le traitement de plaies.
PCT/BR2020/050256 2019-07-13 2020-07-13 Procédé d'obtention d'une composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline, composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline et utilisation dans le traitement de plaies WO2021007635A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
BRBR102019014520-0 2019-07-13
BR102019014520-0A BR102019014520A2 (pt) 2019-07-13 2019-07-13 processo de obtenção de composição liofilizada de nanopartículas a base de quitosana contendo bromelina, composição liofilizada de nanopartículas a base de quitosana contendo bromelina e uso no tratamento de feridas

Publications (1)

Publication Number Publication Date
WO2021007635A1 true WO2021007635A1 (fr) 2021-01-21

Family

ID=74209601

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/BR2020/050256 WO2021007635A1 (fr) 2019-07-13 2020-07-13 Procédé d'obtention d'une composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline, composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline et utilisation dans le traitement de plaies

Country Status (2)

Country Link
BR (1) BR102019014520A2 (fr)
WO (1) WO2021007635A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114107265A (zh) * 2021-11-05 2022-03-01 罗钰玲 一种提取菠萝蛋白酶的工艺

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009155689A1 (fr) * 2008-06-24 2009-12-30 Micropharma Limited Dispositif à base d’oxyde nitrique et procédé de cicatrisation de blessures, traitement de troubles dermatologiques et d’infections microbiennes

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009155689A1 (fr) * 2008-06-24 2009-12-30 Micropharma Limited Dispositif à base d’oxyde nitrique et procédé de cicatrisation de blessures, traitement de troubles dermatologiques et d’infections microbiennes

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "Bromelina: Enzimas proteolíticas do abacaxi", IBEROQUIMICA - BULA DA BROMELINA, 28 September 2020 (2020-09-28), pages 1 - 3, XP009526331, Retrieved from the Internet <URL:https://www.iberomagistral.com.br/Arquivos/Insumo/arquivo-170128.pdf> [retrieved on 20170405] *
ATAIDE JANAíNA ARTEM; GéRIOS ELOAH FAVERO; MAZZOLA PRISCILA GAVA; SOUTO ELIANA B.: "Bromelain-loaded nanoparticles: A comprehensive review of the state of the art", ADVANCES IN COLLOID AND INTERFACE SCIENCE, ELSEVIER, NL, vol. 254, 27 March 2018 (2018-03-27), NL, pages 48 - 55, XP085385875, ISSN: 0001-8686, DOI: 10.1016/j.cis.2018.03.006 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114107265A (zh) * 2021-11-05 2022-03-01 罗钰玲 一种提取菠萝蛋白酶的工艺
CN114107265B (zh) * 2021-11-05 2023-12-01 罗钰玲 一种提取菠萝蛋白酶的工艺

Also Published As

Publication number Publication date
BR102019014520A2 (pt) 2021-01-26

Similar Documents

Publication Publication Date Title
Mohamed et al. Colchicine mesoporous silica nanoparticles/hydrogel composite loaded cotton patches as a new encapsulator system for transdermal osteoarthritis management
Li et al. In situ injectable nano-composite hydrogel composed of curcumin, N, O-carboxymethyl chitosan and oxidized alginate for wound healing application
AU2014224594B2 (en) Powder formulation comprising thrombin and fibrinogen
ES2216543T3 (es) Complejos polimeros de glucuronoglucanos.
WO2012063947A1 (fr) Feuille de gel comprenant un agent gélifiant de type peptide lipidique et composé polymère
ES2383846T3 (es) Composición farmacéutica que comprende S-nitrosoglutatión y un polisacárido
IL268980B (en) Botulinum toxin formulations without albumin
Farhadian et al. Chitosan/gelatin as a new nano-carrier system for calcium hydroxide delivery in endodontic applications: Development, characterization and process optimization
JP2007520424A (ja) ヒアルロン酸ナノ粒子
Badri et al. Biodegradable polymer based nanoparticles: dermal and transdermal drug delivery
Ataide et al. Freeze-dried chitosan nanoparticles to stabilize and deliver bromelain
EP3023105B1 (fr) Nanoparticules lipidiques pour la cicatrisation de plaies
Safdar et al. Preparation, characterization and stability evaluation of ionic liquid blended chitosan tripolyphosphate microparticles
WO2021007635A1 (fr) Procédé d&#39;obtention d&#39;une composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline, composition lyophilisée de nanoparticules à base de chitosane contenant de la broméline et utilisation dans le traitement de plaies
Ahdyani et al. Formulation and characterization of timolol maleate-loaded nanoparticles gel by ionic gelation method using chitosan and sodium alginate
US20100129448A1 (en) Topical hydrogel composition
KR20150128481A (ko) 세포외기질 및 온도감응성 고분자를 포함하는 생체 피부용 조성물
US20090022799A1 (en) Compositions that contain beta-glucan to be used for the prevention and treatment of disease and methods for their use
CN104983722A (zh) 一种皮肤祛疤修复喷膜剂的组合物及其制备方法
JP2016530272A (ja) 微小球体を含む局部用薬物パッチ
Prasanthi et al. A brief review on chitosan and application in biomedical field
Emami et al. Bioactive wound powders as wound healing dressings and drug delivery systems
JP6530392B2 (ja) 相乗効果を有し組織修復を行う微粒子を備えた真皮基質とその製造方法
US20230015373A1 (en) Composition comprising amino acid polymers and a bioactive agent and method of preparing thereof
ES2708976T3 (es) Procedimiento para producir EMD de estabilidad aumentada

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20841004

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20841004

Country of ref document: EP

Kind code of ref document: A1