WO2026028128A1 - Composition gastro-résistante et ses utilisations - Google Patents

Composition gastro-résistante et ses utilisations

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Publication number
WO2026028128A1
WO2026028128A1 PCT/IB2025/057753 IB2025057753W WO2026028128A1 WO 2026028128 A1 WO2026028128 A1 WO 2026028128A1 IB 2025057753 W IB2025057753 W IB 2025057753W WO 2026028128 A1 WO2026028128 A1 WO 2026028128A1
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WIPO (PCT)
Prior art keywords
gastro
previous
resistant composition
composition according
chitosan
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Pending
Application number
PCT/IB2025/057753
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English (en)
Inventor
Paula Isabel TEIXEIRA GONÇALVES COUTINHO BORGES
Sónia Alexandra PEREIRA MIGUEL
Maximiano José PRATA RIBEIRO
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INSTITUTO POLITECNICO DA GUARDA
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INSTITUTO POLITECNICO DA GUARDA
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Publication of WO2026028128A1 publication Critical patent/WO2026028128A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin

Definitions

  • the present disclosure relates to a gastro-resistant composition for protecting bioactive molecules, drugs, or active agents such as microalgae or microalgal compounds, from the acidic environment of the stomach and ensure their release in the intestine.
  • the present disclosure also relates to the use of the gastro-resistant composition as an enteric medicament, a nutraceutical, or a food supplement.
  • Gl gastrointestinal
  • the effective delivery of drugs, active agents, and nutritional supplements to the intestine presents a significant challenge in the field of medicine and biotechnology.
  • the gastrointestinal (Gl) tract is a dynamic environment, characterized by harsh pH levels, the presence of digestive enzymes, and a diverse microbial population. These factors can substantially impact the stability, bioavailability, and efficacy of orally administered compounds.
  • Microalgae are a rich source of bioactive compounds, including proteins, lipids, vitamins, and antioxidants. They have potential applications in health, as food supplements and as therapeutic agents.
  • Microalgae biotechnological potential has been extensively studied in different fields such as bioremediation, cosmetics, biomedical and pharmaceutical industries, as well as in the development of functional foods and food supplements [1-4], Additionally, several microalgae species are recognized as Generally Recognized as Safe (GRAS) and included in the novel foods [5] catalogue, which makes the use of microalgae as cell factories very appealing for pharmaceutical and food purposes [6], Microalgae are unicellular microorganisms, with rapid life cycle, and emerging as promising dietary supplements as diverse array of bioactive compounds.
  • GRAS Generally Recognized as Safe
  • Microalgae are unicellular microorganisms, with rapid life cycle, and emerging as promising dietary supplements as diverse array of bioactive compounds.
  • One of the most important limitations to the application on biomedical field is related with the solubility of bioactive compounds and prevention of their degradation, thereby encapsulation technologies serve to optimize their potential and to achieve higher bioavailability and bioaccessibility [7-9],
  • microalgae and microalgal compounds to the intestine also poses unique challenges due to their sensitivity to Gl tract conditions and the need to preserve their biological activity during transit.
  • microparticles suitable for oral administration of active agents are especially well-suited forthe oral delivery of a wide range of active agents, such as hydrophilic and hydrophobic compounds. These microparticles swell in the small intestine, releasing its payload, while the particle itself is cleared and excreted.
  • Document EP0877604 Al describes a delivery device that releases drugs in the gastrointestinal tract in a location- and time-dependent manner.
  • the composition comprises a drug in combination with a core material, the core being surrounded by a water-insoluble or relatively water-insoluble coating material in which particulate water-insoluble material is embedded.
  • the particulate matter takes up liquid, thus forming channels interconnecting the drug-containing core with the outside of the delivery device. These channels allow the release of drug from the core into the gastrointestinal tract.
  • Document EP4406532 Al discloses a gel formulation for oral administration comprising microalgae biomass capable of adsorbing different drugs in the gastrointestinal tract for treatment of drug intoxications.
  • the integration of microalgae allowed the intestinal drug absorption of different drugs, such as paracetamol, ibuprofen, and alprazolam.
  • the disclosed formulation is designed to facilitate the transport of microalgae biomass through the gastrointestinal tract and to protect it from the acidic gastric environment, thereby enabling drug absorption at the intestinal level.
  • this document is directed to homogeneous gel formulations containing microalgae biomass as a drug adsorbent for detoxification and does not contemplate therapeutic delivery, thus being silent on the release of active agents, namely microalgae biomass, specifically within the intestine.
  • the present disclosure relates to a gastro-resistant composition, preferably a gastro-resistant gel composition, for use as an enteric medicament.
  • the present disclosure is based on the development of a gastro-resistant composition, preferably a gastro-resistant gel composition, for oral administration, for use as an enteric medicament, allowing the delivery of an enteric active agent in the intestine, in particular a bioactive molecule, a drug, or active agent, such as microalgae, microalgae extract and/or microalgal compounds.
  • enteral medicament means a type of pharmaceutical drug or formulation that is specifically designed to bypass the stomach and be released or activated in the intestine.
  • the enteric active agent is directly embedded in the gel formulation.
  • the enteric active agent is encapsulated in particles, preferably in nanoparticles or microparticles, which are further embedded in the gel matrix.
  • the nanoparticles are obtained by nanoprecipitation or nanocomplexation.
  • the disclosed gastro-resistant gel composition protected the bioactive molecules and drugs from the acidic environment of the stomach and ensured their release and enhance bioavailability and bioaccessibility in the intestine.
  • the disclosed gastro-resistant composition provided a controlled release of the active ingredient in order to allow an adequate absorption in the intestine.
  • hydrophilic and/or hydrophobic drugs or bioactive compounds can be incorporated within the matrix of the gastro-resistant composition, preferably a gastro-resistant gel composition.
  • the hydrophilic and/or hydrophobic drugs or bioactive compounds are encapsulated in particles, which are further incorporated within the gel matrix.
  • the enteric active agent was incorporated into particles and the stability and release under different physiological pH (simulated saliva fluid (SSF), Simulated gastric fluid (SGF) and simulated intestinal fluid (SIF)), was assessed.
  • SSF saliva fluid
  • SGF Simulated gastric fluid
  • SIF simulated intestinal fluid
  • the disclosed gastro-resistant formulation preferably a gastro- resistant gel formulation, provides a safe carrier for the particles loaded with the active agents along the gastrointestinal tract, presenting a pH-responsive character, resistant to the acidic gastric environment. This ensures an adequate release and absorption of active compounds in the intestine.
  • the disclosed gastro-resistant gel composition facilitates oral administration, resists gastric pH and releases its cargo in the intestine.
  • the composition withstands the different pH levels characteristic of the physiological environment of the mammalian gastrointestinal tract, due to its qualitative composition based on natural pH-responsive polymers and classified as GRAS. These polymers are biodegradable and are naturally metabolized and excreted by the bodies of living beings. Thus, it can be used to prepare oral preparations for human and/or veterinary use.
  • the disclosed composition provides a unique two-level barrier system that achieves enhanced stability and targeted release of the active ingredient.
  • the gastro-resistant polymeric gel matrix protects the embedded polymeric particles from degradation in the harsh acidic environment of the stomach, ensuring that the active ingredient remains intact during gastric transit. Once the composition reaches the intestine, the gel matrix allows the release of the polymeric particles, which are specifically designed to disintegrate and deliver their cargo at the desired site. This separation of functions— acid protection by the gel and controlled intestinal release by the particles— results in improved robustness against variations in gastric emptying time, enhanced bioavailability of the active ingredient, flexibility in tailoring the particle formulation independently from the gel carrier, and a reliable therapeutic effect.
  • the synergistic interaction between the gel and the particles provides a level of protection and precision that cannot be achieved by either component alone.
  • the present disclosure relates to a gastro-resistant composition for use as an enteric medicament, nutraceutical, or food supplement, wherein said gastro-resistant composition comprises: 5% (w/v) to 60% (w/v) of a polymer selected from carrageenan, pectin, chitosan, gellan gum, dextran, or combinations thereof an effective amount of an enteric active agent, preferably a therapeutically effective amount; wherein the polymer is ionically-crosslinked by calcium chloride, sodium citrate, adipic acid, potassium chloride, gallic acid, tannic acid, vanillin, tripolyphosphate polyanion (TPP), or combinations thereof.
  • the polymer is ionically-crosslinked by calcium chloride, sodium citrate, adipic acid, or combinations thereof.
  • the gastro-resistant composition for use as an enteric medicament, nutraceutical, or food supplement, wherein said gastro- resistant composition comprises: 5% (w/v) to 60% (w/v) of a polymeric matrix comprising a polymer selected from carrageenan, pectin, chitosan, gellan gum, dextran, or combinations thereof; and an effective amount of an enteric active agent, preferably a therapeutically effective amount; wherein the polymeric matrix is ionically-crosslinked by calcium chloride, sodium citrate, adipic acid, potassium chloride, gallic acid, tannic acid, vanillin, tripolyphosphate polyanion (TPP), or combinations thereof; and wherein the active agent is encapsulated in a polymeric particle comprising a polymer selected from carrageenan, pectin, chitosan, gellan gum, dextran or combinations thereof, preferably a combination of at least two polymers.
  • the polymeric matrix is ionically-crosslinked by calcium chloride, sodium
  • the gastro-resistant composition is a gel composition.
  • the polymeric matrix is a gel, preferably a gastro resistant gel.
  • the concentration of polymer in the polymeric matrix ranges from 5 to 55% (w/v), preferably from 15% (w/v) to 50% (w/v) , more preferably 20% (w/v) to 40% (w/v), even more preferably is 20% (w/v) .
  • the concentration of the active agent ranges from 0.5 (w/v) to 6 % (w/v), preferably from 0.51 (w/v) to 4.9% (w/v), more preferably from 1 (w/v) to 4 % (w/v).
  • the composition further comprises 0.5-1.5% (w/v) of xanthan gum and 0.25-1% (w/v) of methylcellulose.
  • the composition further comprises at least one thickening agent, preferably 0.05% - 0.20% (w/v) of at least one thickening agent.
  • the thickening agent is selected from ethylene glycol, mannitol, xylitol, or mixtures thereof.
  • the polymer of the polymeric matrix is a mixture of at least two polymers selected from a list consisting of carrageenan, chitosan, gellan gum, dextran, and pectin; preferably carrageenan and pectin, carrageenan and chitosan, carrageenan and gellan gum, carrageenan and dextran; pectin and chitosan, pectin and gellan gum, pectin and dextran, chitosan and gellan gum, or chitosan and dextran.
  • the gastro-resistant composition comprises 5-20% (w/v) of dextran, preferably 5-15% (w/v) of dextran.
  • the gastro-resistant composition comprises pectin, preferably 5-15% (w/v) of pectin.
  • the gastro-resistant composition comprises 5-20% (w/v) of carrageenan.
  • the polymer of the polymeric particle is selected from a list consisting of gellan gum, chitosan, carrageenan, or mixtures thereof; preferably, the polymer of the polymeric particle is a mixture of gellan gum and chitosan or a mixture of carrageenan and chitosan.
  • the polymer of the polymeric particle is ionically-crosslinked by calcium chloride, tannic acid, vanillin, tripolyphosphate polyanion, or combinations thereof.
  • the particle is a nanoparticle or a microparticle.
  • the average diameter of the nanoparticles ranges from 10- 300 nm, preferably 20-40 nm, measured by Dynamic Light Scattering. In another embodiment, the average diameter of the microparticle ranges from 300-3000 pm, preferably 350-1000 pm, measured by image analysis.
  • the particle comprises 30 to 80% (w/v) of the polymer, preferably 40 to 70% (w/v) of the polymer.
  • composition comprises 30 to 60% (w/v) of chitosan and 5 to 20% (w/v) of gellan gum.
  • the disclosed gastro-resistant composition comprises 10 to 30% (w/w) of the particles.
  • the gastro-resistant composition is administered in the form of a gel, hydrogel, or capsule; preferably is a gastro-resistant gel composition.
  • the active agent is a drug, preferably a hydrophilic or hydrophobic drug.
  • the active agent is selected from a list consisting of: a microalgae biomass, microalgal compounds, microalga extract, or combinations thereof.
  • the active agent is a microalga biomass or extract, preferably a microalga biomass or extract obtained from Chlorella sorokiniana, Chlorella vulgaris, Tetradesmus obliquus, Arthrospira platensis, Tetraselmis chuii, Dunaliella salina, Graesiella emersonii, Haematococcus lacustris, Haematococcus pluvialis, Nannochloropsis oculate, Parachlorella kessleri, Scenedesmus vacuolatus, or mixtures thereof.
  • the active agent is a microalga biomass or extract, preferably a microalga biomass or extract obtained from Chlorella sorokiniana, Chlorella vulgaris, Tetradesmus obliquus, or mixtures thereof.
  • the microalga biomass, microalga extract, or microalga compound is freeze-dried or a paste.
  • the microalgal compound is selected from a list comprising: phycobiliproteins, carotenoids, chlorophylls, polyunsaturated fatty acids, phytosterols, polysaccharides, proteins, vitamins bl2, vitamin E, amino acids, antioxidants, or mixtures thereof.
  • the composition further comprises 0.05% (w/v) to 0.10% (w/v) of at least one preserving agent.
  • at least one preserving agent is selected from a list comprising benzoic acid, sodium benzoate, sorbic acid or benzyl alcohol.
  • the viscosity of the gastro-resistant composition ranges from 30 mPa to 55 mPa, preferably from 35 mPa to 50 mPa, at 21 °C.
  • the present disclosure also related to the use of a gastro-resistant composition for the manufacturing of an enteric medicament; and to a method for treating or preventing a disease in a subject, the method comprising administering the disclosed gastro-resistant composition to the subject.
  • Figure 1 Embodiment of results of viscosity of the disclosed gastro-resistant composition.
  • Figure 2 Degradation profile of an embodiment of the disclosed gastro-resistant composition.
  • Figure 3 Photographic representation of an embodiment of gel formulation with particles encapsulating phycocyanin.
  • Figure 4 Embodiment of results of nanoparticles size distribution.
  • Figure 5 Embodiment of release profile of phycocyanin from the disclosed gastro-resistant composition comprising microparticles in different simulated physiological fluids (saliva, gastric and intestine) along time.
  • the present disclosure relates to a composition for use as an enteric medicament, nutraceutical, or food supplement, wherein said gastro-resistant composition comprises: a polymeric matrix, comprising 5% (w/v) to 60% (w/v) of a polymer selected from carrageenan, pectin, chitosan, gellan gum, dextran, or combinations thereof; an effective amount of an enteric active agent, preferably a therapeutically effective amount; wherein the polymer is ionically-crosslinked by calcium chloride, sodium citrate, adipic acid, potassium chloride, gallic acid, tannic acid, vanillin, TPP or combinations thereof, and wherein the active agent is encapsulated in a polymeric particle comprising a polymer selected from carrageenan, pectin, chitosan, gellan gum, dextran or combinations thereof.
  • the polymer is ionically- crosslinked by calcium chloride, sodium citrate, adipic acid, or combinations thereof.
  • treating encompasses both therapeutic treatment and prophylactic or preventative measures aimed at preventing or slowing down an undesired physiological condition, disorder, ordisease, or achieving beneficial or desired clinical results.
  • Those in need of treatment include those already diagnosed with or suspected of having a disorder.
  • Beneficial or desired clinical results may include, but are not limited to, alleviation of symptoms; reduction in the extent of a condition, disorder, or disease; stabilization of the condition, disorder, or disease; delay in onset or slowing of condition, disorder, or disease progression; amelioration of the condition, disorder, or disease state or remission (whether partial or total), whether detectable or undetectable; improvement in at least one measurable physical parameter, not necessarily noticeable by the patient; or enhancement or improvement of the condition, disorder, or disease.
  • Treatment includes eliciting a clinically significant response without excessive levels of side effects and includes prolonging survival compared to expected survival without treatment.
  • terapéuticaally effective amount refers to the quantity of a compound that, when administered, is sufficient to prevent the development of, or alleviate to some extent, one or more symptoms of a disorder, disease, or condition being treated. It also refers to the amount of a compound sufficient to elicit the desired biological or medical response in a cell, tissue, system, animal, or human, as sought by a researcher, veterinarian, medical doctor, or clinician.
  • the gel composition was produced by using GRAS and pH responsive natural polymers such as carrageenan, pectin, chitosan, gellan gum, dextran, or combinations thereof.
  • the gastro-resistant composition comprises a polymeric matrix, comprising 5% (w/v) to 60% (w/v) of a polymer selected from carrageenan, pectin, chitosan, gellan gum, dextran, or combinations thereof; preferably 15% (w/v) to 60% (w/v) of the polymer, more preferably 20% (w/v) of polymer.
  • the gastro-resistant gel composition may further comprise xanthan gum, methylcellulose, or combinations thereof.
  • the gastro-resistant composition further comprises particles, in particular nanoparticles or microparticles, to encapsulate the active ingredient, providing protection and controlled release on the desired local of the intestine.
  • the particles are prepared from natural polymers such as carrageenan, pectin, chitosan, gellan gum, dextran or combinations thereof.
  • each polymer is dissolved separately and then added together.
  • the gel composition and the particles are obtained by ionic gelation with cross-linkers like calcium chloride, tripolyphosphate polyanion, sodium citrate, adipic acid, potassium chloride, gallic acid, tannic acid, vanillin or combinations thereof.
  • cross-linkers like calcium chloride, tripolyphosphate polyanion, sodium citrate, adipic acid, potassium chloride, gallic acid, tannic acid, vanillin or combinations thereof.
  • the composition further comprises from 0.05% to 0.20% (w/v) of at least one thickening agent selected from ethylene glycol, mannitol or xylitol.
  • the composition comprises 0.05% - 0.20% (w/v) of the at least one thickening agent; preferably 0.05 to 0.15% (w/v) of the at least one thickening agent.
  • the active agent is incorporated in the gel formulation.
  • the active agent is a drug or microalgae biomass or microalgal compounds.
  • the microalga is added to the gel formulation as a paste or freeze-dried.
  • the microalgal compound is selected from a list comprising: phycobiliproteins, such asphycocyanin, or phycoerythrin, carotenoids, such as astaxanthin, beta-carotene, lutein, orfucoxanthin, chlorophylls, polyunsaturated fatty acids (pufas), phytosterols, polysaccharides, proteins, vitamins bl2, vitamin E, amino acids, antioxidants, or mixtures thereof.
  • phycobiliproteins such asphycocyanin, or phycoerythrin
  • carotenoids such as astaxanthin, beta-carotene, lutein, orfucoxanthin
  • chlorophylls polyunsaturated fatty acids (pufas)
  • phytosterols polysaccharides
  • proteins vitamins bl2, vitamin E, amino acids, antioxidants, or mixtures thereof.
  • the enteric active agent is encapsulated in polymeric particles, preferably nanoparticles or microparticles.
  • the polymeric particles are made of at least one polymer selected from carrageenan, pectin, chitosan, gellan gum, dextran, or combinations thereof.
  • the particles have an average diameter size ranging from 10 nm to 3000 pm, preferably from 30 nm to 500 pm, more preferably from 350 pm to 500 pm.
  • the average diameter size of nanoparticles (10-300nm) was measured by Dynamic Light Scattering, and the average diameter size of microparticles was measured by image analysis using Fiji Software.
  • the cross-linker used to obtain the particles is selected from a list comprising calcium chloride, sodium citrate, tripolyphosphate, adipic acid, potassium chloride, gallic acid, tannic acid, vanillin, TPP, among others.
  • the disclosed gel composition is suitable for use as an oral enteric medicament, in particular a medicament for use in the treatment of intestinal disorders in humans or animals, therefore finding application in pharmaceutical, medical, nutraceutical and veterinary technical fields.
  • Gastro-resistant gel composition with hydrophilic and/or hydrophobic drugs a) Gel formulation composition
  • the gastro-resistant gel formulation was prepared by mixing pectin, carrageenan, and dextran, in different concentrations and ratios, acting as a functional carrier of hydrophilic and hydrophobic bioactive agents and drugs, throughout the gastrointestinal tract.
  • xanthan gum 0.5-1.5% (w/v)
  • methylcellulose 0.25-1% (w/v)
  • the polymers were dissolved separately in water in different concentrations and the blends were prepared using the volume ratios according to Table 1.
  • solutions of potassium chloride (0.5%-2% (w/v)), gallic acid (0.5%-2% (w/v)), calcium chloride (0.5%-2% (w/v)), sodium citrate (0.5%-2% (w/v)), or adipic acid (10%- 15% (w/v)) were used.
  • the resulting compositions comprised 5% (w/v) to 60% (w/v) of the select polymer, or polymers.
  • the air is removed from the obtained mixture by sonication and/or vacuum.
  • the viscosity was measured using a rheometer ( Figure 1). Briefly, a sample of the gastro-resistant composition was placed in a suitable container, and the measurement took place at room temperature, preferably at 21°C. The shear rate was incrementally increased, progressing to the maximum of 1120 (1/s), and viscosity measured at different shear rate values. Mean viscosity was calculated over the entire shear rate range. As depicted in Figure 1, the maximum shear rate registered was approximately 1120 (1/s) with mean viscosity of approximately 16 mPa.
  • room temperature should be regarded as a temperature between 15-30 °C, preferably between 18-25 °C, more preferably between 20-22 °C.
  • the gel degradation profile in contact with simulated fluids in particular simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), was characterized with the incubation of the gel formulation (ImL) with 10 ml of fluids at 37°C under agitation (75 rpm/min). This was performed for 60 and 120 minutes with SGF, and then transferred to SIF and collected at 135 and 150 minutes. The samples were freeze-dried and the degradation was calculated by using the following equation: 100
  • Wj the initial weight
  • W t is the weight of the sample collected at the specific timepoint.
  • SGF and SIF were prepared using sodium chloride and hydrochloric acid at pH 1.6, and sodium hydroxide, monobasic potassium phosphate and pancreatin at pH 6.8, respectively.
  • microparticles were produced through ionic precipitation by inducing the interaction between gellan gum and calcium chloride, as crosslinker (Table 2).
  • a gellan gum solution (0.25%-l% (w/v)) was prepared by dissolving in deionized water at 50°C. After, this solution was added dropwise into a solution comprising calcium chloride (3-5% (w/v)) dissolved in a chitosan solution (0.25-0.8% (w/v)). Hydrophilic and/or hydrophobic bioactives and drugs were incorporated into the polymeric solutions, according to its polarity.
  • the microparticles After the production of the microparticles, they were immersed in a TPP solution (1.5-2% (w/v)) and then washed with water to improve the pH responsiveness, assuring the controlled release in physiological pH for intestinal delivery of the bioactives and/or drugs.
  • microparticles were then incorporated in the gel formulation composition, as depicted in Figure 3.
  • nanoparticles were produced through ionic precipitation by inducing the interaction between gellan gum and calcium chloride, as crosslinker (Table 3).
  • a solution comprising calcium chloride (3-5% (w/v)) dissolved in chitosan solution (0.25-0.8% (w/v)) was prepared.
  • this solution was added dropwise into a gellan gum solution (0.25%-l% (w/v)) prepared by dissolving in deionized water at 50°C, under agitation.
  • Hydrophilic and/or hydrophobic bioactives or drugs were incorporated into the polymeric solutions, according to its polarity.
  • nanoparticles can also be prepared by flash nanocomplexation technique by the interaction between the anionic polysaccharides such as carrageenan and gellan gum and the positive charge of amine groups available on the chitosan backbone, and as a result of the rapid and turbulent mixing between the anionic polymers.
  • the nanoparticles are prepared using a solution of the anionic polymer at a concentration of 0.05-1.5% (w/v) and a solution of chitosan at a concentration of 0.05-1.5% (w/v), in a volume ratio of 1:2-1:4.
  • the drugs or the bioactive compounds (at a concentration of 1 mg/mL-3 mg/mL) were incorporated into the polymers before the nanoprecipitation process.
  • Crosslinkers described above can be used as a collecting and stabilising solution of the nanosystems.
  • the size of the nanoparticles was determined by Dynamic Light Scattering technique.
  • the mean diameter of the carrageenan and chitosan nanoparticles was 230.5 nm with a polydispersity index value of 0.432, evidencing its suitability to be used as carrier for drug/bioactive compounds deliver at intestine ( Figure 4).
  • phycocyanin was used as hydrophilic compound model.
  • the agent was incorporated into the polymeric microparticles, and the encapsulation efficiency determined immediately after microparticles production. Briefly, an aliquot of supernatant was collected containing non-encapsulated phycocyanin, and the amount of phycocyanin was determined through the following equation, as described by Bennett and Bogard (1973) [10],
  • Phycocyanin (PC) ((Abseis - 0.474 + Abs6so))/5.34 Eq. 1 where Agis and Asso a e the absorbance readings at 615 and 650 nm, respectively.
  • EE(%) ((Total PC - Free PC)/Total PC) * 100 Eq. 2 where "Total PC” and “Free PC” were the PC concentration in the microparticles and the amount of PC previously determined, respectively.
  • the gastro-resistant composition comprising microparticles was immersed in simulated saliva fluid (during 30 min), simulated gastric fluid (during 2h), simulated intestinal fluid (during 3h) and at specific timepoints, 200 pl of solution was collected and the concentration of the released phycocyanin was determined by using the Equation 1. The obtained results are presented in Figure 5.
  • Gastro-resistant gel composition with microalgae a) Culture of Microalgae and encapsulation
  • selected microalgae were cultivated using methods known in the state of the art, where the culture conditions (culture medium, pH, light) were optimized for biomass production, in batch and/or semicontinuous cultures according to the approach previously validated for different species [11,12,13], Then, the microalgae biomass was harvested, centrifuged, and freeze-dried, following the conditions described in literature [14,15], Depending on the application, the biomass can be directedly incorporated in the gastro-resistant composition, either embedded in its matrix or encapsulated in particles, or subjected to extraction techniques of bioactive compounds by using methods known in the state of the art.
  • microalgae biomass paste or freeze-dried
  • bioactive compounds both hydrophilic and hydrophobic

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Abstract

La présente invention concerne une composition destinée à être utilisée en tant que médicament entérique, nutraceutique ou complément alimentaire, ladite composition gastro-résistante comprenant : 5 % (p/v) à 60 % (p/v) d'une matrice polymère, comprenant un polymère choisi parmi le carraghénane, la pectine, le chitosane, la gomme gellane, le dextrane, ou des combinaisons de ceux-ci; une quantité efficace d'un principe actif entérique, de préférence une quantité thérapeutiquement efficace; le polymère étant ioniquement réticulé par du chlorure de calcium, du citrate de sodium, de l'acide adipique, du chlorure de potassium, de l'acide gallique, de l'acide tannique, de la vanilline, du polyanion tripolyphosphate ou des combinaisons de ceux-ci; et le principe actif étant encapsulé dans une particule polymère comprenant un polymère choisi parmi le carraghénane, la pectine, le chitosane, la gomme gellane, le dextrane ou des combinaisons de ceux-ci, de préférence une combinaison d'au moins deux polymères.
PCT/IB2025/057753 2024-07-30 2025-07-30 Composition gastro-résistante et ses utilisations Pending WO2026028128A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PT119629 2024-07-30
PT11962924 2024-07-30

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WO2026028128A1 true WO2026028128A1 (fr) 2026-02-05

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0877604A1 (fr) 1996-01-18 1998-11-18 Perio Products Ltd Systeme pour l'administration de medicaments dans le tube digestif
CN101744760A (zh) * 2008-12-18 2010-06-23 梁颖 用于难溶性或易分解性药物的缓释体
US20190175507A1 (en) 2016-06-03 2019-06-13 Tamarisk Technologies Group Llc Compositions for oral administration of active agents
EP4406532A1 (fr) 2023-01-27 2024-07-31 Instituto Politécnico da Guarda Formulation de gel pour le traitement d'intoxication médicamenteuse et son procédé d'obtention

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0877604A1 (fr) 1996-01-18 1998-11-18 Perio Products Ltd Systeme pour l'administration de medicaments dans le tube digestif
CN101744760A (zh) * 2008-12-18 2010-06-23 梁颖 用于难溶性或易分解性药物的缓释体
US20190175507A1 (en) 2016-06-03 2019-06-13 Tamarisk Technologies Group Llc Compositions for oral administration of active agents
EP4406532A1 (fr) 2023-01-27 2024-07-31 Instituto Politécnico da Guarda Formulation de gel pour le traitement d'intoxication médicamenteuse et son procédé d'obtention

Non-Patent Citations (18)

* Cited by examiner, † Cited by third party
Title
BENNETT, A.BOGORAD, L.: "Complementary chromatic adaptation in a filamentous blue-green alga", THE JOURNAL OF CELL BIOLOGY, vol. 58, no. 2, 1973, pages 419 - 435
COUTINHO P, FERREIRA M, FREIRE I, OTERO A: "Enriching Rotifers with "Premium" Microalgae:Rhodomanas lens", MARINE BIOTECHNOLOGY, vol. 22, no. 1, 1 February 2020 (2020-02-01), pages 118 - 129
COUTINHO PALVES, AMARTINS, IRIBEIRO, MPRODRIGUES, MARAUJO, ARTS: "PW199 Effects of 17-b-estradiol and diclofenac on growth and chlorophyllcontent of Chlorella vulgaris", 8TH CONGRESS OF EUROPEAN MICROBIOLOGISTS - FEMS 2019, 7 July 2019 (2019-07-07)
DA SILVA, A. F.MOREIRA, A. F.MIGUEL, S. F.COUTINHO, P.: "Recent advances in microalgae encapsulation techniques for biomedical applications", ADVANCES IN COLLOID AND INTERFACE SCIENCE, vol. 333, 2024, pages 103297
DOMINGUEZ AFERREIRA MCOUTINHO PFABREGAS JOTERO A: "Delivery of astaxanthin from Haematococcus pluvialis to the food chain", AQUACULTURE, vol. 250, 1 January 2005 (2005-01-01), pages 424 - 430
GARCIA J L ET AL: "Microalgae, old sustainable food and fashion nutraceuticals", MICROBIAL BIOTECHNOLOGY,, vol. 10, no. 5, 1 September 2017 (2017-09-01), pages 1017 - 1024, XP009513178, ISSN: 1751-7907, [retrieved on 20170815], DOI: 10.1111/1751-7915.12800 *
GARCÍA JLDE VICENTE MGALÁN B: "Microalgae, old sustainable food and fashion nutraceuticals", MICROBIAL BIOTECHNOLOGY, vol. 10, no. 5, 2017, pages 1017 - 1024, XP009513178, DOI: 10.1111/1751-7915.12800
GARG, D.BALA, S.PHUTELA, U. G.: "Microalgal nutraceuticals: unravelling solution to food-health nexus", PHYTOCHEMISTRY REVIEWS, vol. 23, no. 2, 2024, pages 321 - 348
HABIBZADEH MCHAIBAKHSH NNAEEMI AS: "Optimized treatment of wastewater containing cytotoxic drugs by living and dead biomass of the freshwater microalga, Chlorella vulgaris", ECOLOGICAL ENGINEERING, vol. 111, 1 February 2018 (2018-02-01), pages 85 - 93
HU HZHONG DLI WLIN XHE JSUN YWU YSHI MCHEN XXU F: "Microalgae-based bioactive hydrogel loaded with quorum sensing inhibitor promotes infected wound healing", NANO TODAY, vol. 42, 1 February 2022 (2022-02-01), pages 101368
ISMAIL DPRAKASA MNUGROHO P, THE EFFECT OF ADDING MICROALGAE EXTRACT SPIRULINA PLATENSIS CONTAINING FLAVONOID IN THE FORMATION OF SUNSCREEN TOWARDS CREAM STABILITY AND SPF VALUES, pages 22552020
MIGUEL SPRIBEIRO MPOTERO ACOUTINHO P: "Application of microalgae and microalgal bioactive compounds in skin regeneration", ALGAL RESEARCH, vol. 58, 1 October 2021 (2021-10-01), pages 102395
NOVEL FOOD STATUS CATALOGUE (NEW, 29 July 2024 (2024-07-29), Retrieved from the Internet <URL:https://food.ec.europa.eu/safety/novel-food/novel-food-status-catalogue_en>
PAPADAKI, S.TRICHA, N.PANAGIOTOPOULOU, M.KROKIDA, M.: "Innovative Bioactive Products with Medicinal Value from Microalgae and Their Overall Process Optimization through the Implementation of Life Cycle Analysis-An Overview", MARINE DRUGS, vol. 22, no. 4, 2024, pages 152
PROSENC FPIECHOCKA JSKUFCA DHEATH EGRIESSLER BULC TLSTENIČ DBUTTIGLIERI G: "Microalgae-based removal of contaminants of emerging concern:Mechanisms in Chlorella vulgaris and mixed algal-bacterial cultures", JOURNAL OF HAZARDOUS MATERIALS, vol. 418, 15 September 2021 (2021-09-15), pages 126284
RIBEIRO M P ET AL: "Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing", MATERIALS SCIENCE AND ENGINEERING C, ELSEVIER SCIENCE S.A, CH, vol. 33, no. 5, 24 March 2013 (2013-03-24), pages 2958 - 2966, XP028584741, ISSN: 0928-4931, DOI: 10.1016/J.MSEC.2013.03.025 *
SANTAEUFEMIA STORRES EMERA RABALDE J: "Bioremediation of oxytetracycline in seawater by living and dead biomass of the microalga Phaeodactylum tricornutum", JOURNAL OF HAZARDOUS MATERIALS, vol. 320, 15 December 2016 (2016-12-15), pages 315 - 325
ZHANG SHANGWEN ET AL: "Carboxymethyl chitosan microspheres loaded hyaluronic acid/gelatin hydrogels for controlled drug delivery and the treatment of inflammatory bowel disease", INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, ELSEVIER BV, NL, vol. 167, 18 November 2020 (2020-11-18), pages 1598 - 1612, XP086440336, ISSN: 0141-8130, [retrieved on 20201118], DOI: 10.1016/J.IJBIOMAC.2020.11.117 *

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