Production method for a transdermal food supplement from nanofibers

Abstract

The invention relates to a method for producing a transdermal food supplement, wherein an active ingredient is encapsulated in a nanofiber structure via electrospinning, thereby allowing the release of the active ingredient to maintain sustained release over time.

Description

[0001] PRODUCTION METHOD FOR A TRANSDERMAL FOOD SUPPLEMENT FROM NANOFIBERS

[0002] Technical Field

[0003] The invention relates to a method for producing a transdermal food supplement, wherein an active ingredient is encapsulated in a nanofiber structure via electrospinning, thereby allowing the release of the active ingredient to maintain sustained release over time.

[0004] Prior Art

[0005] Food supplements are generally taken orally and are in the form of tablets, pills, or syrup. In some cases, it is also possible for them to be administered under a doctor's supervision in the form of an intravenous serum or as an injection with a needle.

[0006] The characteristics of orally taken food supplements — their passing to the intestines after spending 2-3 hours in the stomach, their mixing into the blood within 2-3 hours after passing to the intestines, and the expected effect not being continuous and at the same level but rather reaching a peak point and then decreasing — have been described in many studies in the literature. Due to a number of reasons, such as the active and bioactive substances that are expected to exhibit the effects of food supplements not being resistant to stomach acidity (pH approximately 2) and the matrix effect, generally 50% of the concentration expected to mix into the blood in the intestines and of the expected beneficial effect is observed. The concentration of the active ingredient that mixes into the blood from the intestines decreases after reaching a maximum level in the blood. The fact that the expected effect is both seen hours later and does not last for a very long time shows that orally taken food supplements are not very effective. Because almost half, and sometimes more, is broken down by the time it mixes into the blood, the concentration of active ingredients taken as one dose in the form of a tablet, pill, or syrup is too high to be given directly into the blood. This also, in fact, shows that oral administration is not effective and that almost half of it is wasted. Transdermal food supplements, compared to oral administration, are both at a lower dose and are an application that can mix directly into the blood when it passes the skin layers. However, here there are problems of the active ingredient mixing directly into the blood suddenly and in a high dose (burst release). For this, it can be ensured that the active ingredient is micro / nano-encapsulated by various methods using polymers and that the release is controlled, for a long time, and at the same level (controlled, sustained and longterm release).

[0007] US11357710B2 discloses a solid mask and a method for producing this mask.

[0008] When the studies existing in the prior art are examined, a need has been arisen for the development of a method for producing a transdermal food supplement wherein an active ingredient is encapsulated in a nanofiber structure via electrospinning, and which thereby allows the release of the active ingredient to maintain sustained release over time.

[0009] Objectives of the Invention

[0010] The object of this invention is to develop a method for producing a transdermal food supplement wherein an active ingredient is encapsulated in a nanofiber structure via electrospinning, thereby allowing the release of the active ingredient to maintain sustained release over time.

[0011] A further object of the present invention is to develop a method for producing a transdermal food supplement that allows the release of the active ingredient to begin within a very short period of time (within 5-10 minutes), in comparison to oral administration.

[0012] A further object of the present invention is to develop a method for producing a transdermal food supplement in which unwanted burst release can be prevented.

[0013] A further object of the present invention is to develop a method for producing a transdermal food supplement that facilitates the passage of the active ingredient through the lipid-containing layers of the skin. Detailed Description of the Invention

[0014] A method for producing a transdermal food supplement, wherein the active ingredient is encapsulated in a nanofiber structure via electrospinning, thereby enabling the release of the active ingredient to maintain sustained release over time, it comprises;

[0015] a) preparing solutions, emulsions, or double emulsions containing 1-5% by weight of an active ingredient, 5-30% by weight of a polymer / biopolymer or mixtures thereof, and the remainder as 65-94% of a solvent or solvent mixtures,

[0016] b) producing uniaxial and coaxial nanofibers from the prepared polymer solutions, or from the polymer-containing emulsions or double emulsions, via electrospinning,

[0017] c) producing the transdermal food supplement by fabricating the resulting uniaxial or coaxial nanofibers as a single layer, or by producing them layer- by-layer on top of one another.

[0018] In the method that is the subject of the invention; solutions, emulsions, or double emulsions are prepared, comprising 1-5% by weight of an active ingredient, 5-30% by weight of a polymer / biopolymer or mixtures thereof, with the remainder being 65-94% of a solvent or solvent mixtures. In the case that an emulsion is prepared, the solvents are prepared so as to also include oil.

[0019] Examples of the prepared mixtures include pullulan-sodium alginate (solvent: water), pullulan-pectin (solvent: water), pullulan-inulin (solvent: water-ethyl alcohol), zein (water-ethyl alcohol), gelatin (water-acetic acid), gelatin-collagen (water-ethyl alcohol), gelatin-collagen-hyaluronic acid (water-ethyl alcohol), gelatin-pectin (water-acetic acid), gelatin-sodium alginate (water-acetic acid), gelatin-chitosan (water-acetic acid), gelatin-cellulose acetate (water-acetic acid), gelatin-lactalbumin (water-acetic acid), keratin (dimethyl sulfoxide-acetone), polyvinyl alcohol (water), gelatin-polyvinyl alcohol (water-acetic acid), or polycaprolactone (acetone-acetic acid). The specified synthetic or biopolymers or mixtures thereof are stirred for 2-6 hours at 40-60 °C in the solvents specified in parentheses. Afterwards, 1-5% of the active ingredient is added according to the type of polymer. This mixture is obtained as uniaxial nanofibers on a collector plate at a distance of 5-20 cm by being fed into an electrospinning device at a flow rate in the range of 0.5-1.5 ml / h and by applying a voltage in the range of 5-35 kV. The thickness of the nanofiber layer, and consequently the amount of the active ingredient, can be adjusted according to the production time of these nanofibers. By bringing this uniaxial nanofiber layer into direct contact with the skin, the passage of the active ingredient from the skin into the bloodstream is enabled. While the uniaxial nanofiber layer can be of different thicknesses, it can also be obtained as two or three different uniaxial nanofiber layers on top of one another (i.e., in successive layers). To prevent the sudden release of the active ingredient into the blood (burst release) and to make the active ingredient release long-lasting, one of the nanofiber layers can be produced without containing the active ingredient.

[0020] With the same polymer or polymer mixtures, coaxial nanofibers can be produced with the active ingredient on the inner side. In the production of coaxial nanofibers, the electrospinning process involves two separate feeding mechanisms. The active ingredient for the inner part and the polymer or polymer mixture for the outer part are pumped separately to the nozzle where voltage is applied. The flow rate of the active ingredient for the inner part is slower, at half or one-third the rate of the polymer solution pumped for the outer part. The applied voltage ranges and the collector plate distance range are the same as in the production of uniaxial nanofibers.

[0021] In the production of uniaxial and coaxial nanofibers, the feeding solutions can also be an emulsion or a double emulsion. The release of the active ingredient to the skin from nanofibers obtained from an emulsion or double emulsion occurs more easily, due to the oil content in the emulsion, as the skin is also hydrophobic in nature.

[0022] In the production of uniaxial nanofibers, after the hydrophilic polymer or polymer mixture is dissolved in water, it is mixed with the active ingredient (an emulsion can also be obtained without the addition of the active ingredient) and an emulsifier such as lecithin or polyglycerol polyricinoleate in a range of 0.5-1%, and is dispersed at high speed in olive oil, sunflower oil, or a vegetable oil. In this way, a polymer or polymer mixture in an emulsion structure containing the active ingredient is obtained. Nanofibers are obtained via electrospinning under the same conditions as in the production of uniaxial nanofibers.

[0023] For a double emulsion, after the hydrophilic polymer or polymer mixture is dissolved in water, it is mixed with the active ingredient (an emulsion can also be obtained without the addition of the active ingredient) and an emulsifier such as lecithin or polyglycerol polyricinoleate in a range of 0.5-1%, and is dispersed at high speed in olive oil, sunflower oil, or a vegetable oil. Subsequently, this mixture is mixed with water to obtain a double emulsion (wl / o / w2). With this double emulsion, the production of uniaxial and coaxial nanofibers is carried out in the manner described above.

[0024] In the method that is the subject of the invention, examples of the active (active / bioactive) ingredients to be encapsulated in the nanofiber include: NaCl (can be used to provide electrolyte balance); isotonic, hypotonic, and hypertonic serums (can be used for dehydration); bee products such as propolis, royal jelly, or their active ingredients; essential fatty acids (e.g., omega-3 and omega-6 fatty acids); medicinal and aromatic oils (e.g., St. John's wort oil, black seed oil, etc.); plant, fruit, vegetable, and spice extracts, or their active ingredients with anticancer, antimicrobial, antioxidant, anti-inflammatory properties (e.g., hesperidin in St. John's wort, resveratrol in grapes, catechins in the tea plant, etc.); antioxidants (glutathione, ginkgo, coenzyme Q10, quercetin, etc.), minerals (iron, copper, zinc, magnesium, calcium, selenium, chromium or their compounds, etc.), vitamins (B group, C, A, D, E, K, folic acid, etc.), amino acids; peptides; bioactive peptides, aroma components, etc.

[0025] In the method that is the subject of the invention, the production of uniaxial nanofibers consists of the following steps. - Emulsions or double emulsions of synthetic polymers, biopolymers, or mixtures thereof (at a concentration of 5-30%, w / v), containing the active (bioactive) ingredient, are prepared using a suitable solvent or solvent mixtures.

[0026] - This prepared feeding solution or emulsion is placed in a syringe and, by means of a micropump (at flow rates in the range of 0.01-3 mL / h), is jetted upwards from a needle tip to which a voltage or potential difference in the range of 5-35 kV is applied.

[0027] - The distance between the needle tip and a stationary or moving collector plate made of a conductive metal is adjusted to 5-20 cm.

[0028] - During the process, the solvent of the feeding solution, which is jetted from the voltage-applied needle tip by means of a micropump, evaporates, and the active ingredient and polymer are collected on the collector plate in the form of nanometer-diameter fibers.

[0029] - During the process, the temperature can be ambient temperature or it can be maintained constant at 20-25 °C.

[0030] - During the process, the humidity may be the natural ambient humidity, or if the environment is humid, the humidity can be reduced according to the polymers used. Ventilation may be applied to remove the solvent that evaporates during the process and / or to reduce the humidity.

[0031] The production of coaxial nanofibers comprises the following steps:

[0032] - The active ingredient is prepared by being dissolved in water or oil. The active ingredient concentration is prepared as w / v (weight / volume), at a concentration that is dependent on the active ingredient and is required to meet the amounts permitted in the Turkish Food Codex.

[0033] - The synthetic polymer, biopolymer, or mixtures thereof are prepared at a concentration of 5-30% (w / v) using a suitable solvent.

[0034] - In the coaxial needle system, two micropumps are used.

[0035] - The active ingredient solution is pumped to the inner needle of the coaxial needle system by a micropump. - The polymer solution is pumped to the outer part of the coaxial needle system by another micropump.

[0036] Simultaneously, both the active ingredient solution and the polymer solution are pumped upwards from the needle tip, and a voltage (potential difference) is applied to the needle tip.

[0037] - The solvent evaporates during the process, and the coaxial nanofiber structure is collected on the stationary or moving collector plate.

[0038] - The process parameters are the core flow rate, the shell flow rate, the applied voltage, and the collector plate distance.

Claims

CLAIMS1. A method for producing a transdermal food supplement, wherein the active ingredient is encapsulated in a nanofiber structure via electrospinning, thereby enabling the release of the active ingredient to maintain sustained release over time, characterized in that it comprises;- preparing solutions, emulsions, or double emulsions containing 1- 5% by weight of an active ingredient, 5-30% by weight of a polymer / biopolymer or mixtures thereof, and the remainder as 65- 94% of a solvent or solvent mixtures,- producing uniaxial and coaxial nanofibers from the prepared polymer solutions, or from the polymer-containing emulsions or double emulsions, via electrospinning,- producing the transdermal food supplement by fabricating the resulting uniaxial or coaxial nanofibers as a single layer, or by producing them layer-by-layer on top of one another.

2. The method for producing a transdermal food supplement according to claim 1, characterized in that the prepared solutions or emulsions comprise 1-5% by weight of an active ingredient, 5-30% by weight of a polymer / biopolymer or mixtures thereof, and 65-94% by weight of a solvent or solvent mixtures.

3. The method for producing a transdermal food supplement according to claim 2, characterized in that the prepared solutions or emulsions are stirred in the solvent for 2-6 hours at 40-60 °C.

4. The method for producing a transdermal food supplement according to claim 3, characterized in that, in the production of uniaxial nanofibers, the electrospinning is performed at a flow rate in the range of 0.5-1.5 ml / h by applying a voltage in the range of 5-35 kV.