Biopolymer formulations for drug delivery

Abstract

This specification describes a formulation comprising a homogeneous suspension of a biopolymer(s) for drug delivery of an active molecule. In an embodiment, the biopolymer is selected from chitin, chitosan, cellulose, hemicellulose, lignin, amylose, actin, fibrin, collagen, silk, fibroin, keratin, wool, alginic acid, and mixtures thereof. In an embodiment, the biopolymer is mechanically treated with an API under high shear conditions and / or high mechanical energy. The formulation can find particular use in drug delivery systems that involve the transport and release of compounds or molecules for purposes such as pharmaceuticals, drug substances, cosmetics, and the like.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the priority of U.S. Provisional Patent Application 63 / 356,703, filed on June 29, 2022, the entire content of which is incorporated herein by reference.

[0002] (Field of the Invention) The present invention relates to the fields of therapy and cosmetics, and more particularly to a new formulation consisting of a homogeneous suspension of biopolymers for the drug delivery of active molecules.

Background Art

[0003] Drug delivery systems (DDSs) are used to control the rate at which a drug is released and the location within the body where the drug is released. In this regard, there is always a need for new approaches, formulations, manufacturing techniques, storage systems, and scientific technologies that can better transport pharmaceutical compounds to their target sites in order to achieve the desired therapeutic effect.

[0004] Natural polymers or biopolymers have gained popularity as carriers for drug delivery because they offer more advantages than conventional polymers. Biopolymers are non - toxic and biocompatible, making them versatile carriers. They are relatively inexpensive, providing an economic advantage. Biopolymers are biodegradable, providing an environmental advantage. However, the most abundant biopolymers, such as cellulose and chitin, are insoluble, thereby limiting and complicating their use. Advantageously, the applicant has described in WO 2022 / 137184 a novel homogeneous suspension of biopolymers that is homogeneous, stable, and finds numerous uses in DDSs.

[0005] Therefore, there is still a need for new methods of incorporating biopolymers into DDSs.

[0006] There is still a need for drug delivery compositions that include natural, biocompatible, biodegradable, non-toxic components such as cellulose, chitin, and the like.

[0007] The present invention addresses these and other needs, as will become apparent from a review of the disclosure and the description of the features of the invention below. SUMMARY OF THE INVENTION

[0008] According to one aspect, the present invention relates to a composition for delivering a pharmaceutical active ingredient (API) comprising a biopolymer and at least one API.

[0009] According to another aspect, the present invention is a method of delivering a pharmaceutical active ingredient (API) to a subject in need thereof, comprising: (i) providing a composition as defined herein; and (ii) administering the composition to the subject. The present invention relates to a method comprising the above.

[0010] According to another aspect, the present invention is a method of locally delivering a pharmaceutical active ingredient (API) to a subject in need thereof, comprising: (i) providing a delivery composition comprising a biopolymer and at least one API as defined herein; and (ii) applying the composition to the body of the subject. The present invention relates to a method comprising the above.

[0011] According to another aspect, the present invention is a method of orally delivering a pharmaceutical active ingredient (API) to a subject in need thereof, comprising: (i) providing a mixture comprising an API mixed in a biopolymer composition; and (ii) drying the mixture to obtain a dried product; and (iii) orally administering the dried product to the subject. The present invention relates to a method comprising the above.

[0012] According to another aspect, the present invention is a method for manufacturing a delivery composition as defined herein, which comprises mechanically treating an API and a biopolymer(s) together under high shear conditions and / or high mechanical energy to obtain a stable homogeneous aqueous composition.

[0013] Additional aspects, advantages, and features of the present invention will become more apparent upon reading the following non-limiting description of preferred embodiments, which are exemplary and should not be construed as limiting the scope of the present invention.

Brief Description of the Drawings

[0014] For ease of understanding the present invention, embodiments of the present invention are exemplarily shown in the accompanying drawings.

[0015]

Figure 1

[0016]

Figure 2

[0017]

Figure 3

[0018] Further details of the present invention and its advantages will become apparent from the detailed description included below.

[0019] Detailed Description of Embodiments In the following description of embodiments, reference to the accompanying drawings is illustrative of examples in which the present invention can be practiced. It will be understood that other embodiments can be made without departing from the scope of the disclosed invention. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0020] Summary In PCT Publication WO 2022 / 137184, entitled "HOMOGENEOUS BIOPOLYMER SUSPENSIONS, PROCESSES FOR MAKING SAME AND USES THEREOF" (the entire content of which is incorporated herein by reference), the applicant describes the preparation of stable homogeneous suspensions of insoluble and / or semi-soluble biopolymers.

[0021] The inventor(s) has shown that the biopolymer suspensions according to the present invention have the ability to retain hydrophilic and hydrophobic molecules, which makes these suspensions useful in drug delivery systems (DDS) as drug delivery vehicles for transporting and releasing target molecules such as pharmaceutical active ingredients (API) and / or other molecule(s). The biopolymer suspensions of the present invention can be particularly useful considering the minimum components required in the suspension, thereby reducing the possibility of unwanted interactions between the vehicle (i.e., the suspension components) and the API. The present invention includes, but is not limited to, the general specific compositions described in WO 2022 / 137184.

[0022] Accordingly, the present invention generally relates to the use of homogeneous suspensions of biopolymers for drug delivery. As used herein, the term "drug delivery" generally means transporting and releasing a target compound or molecule such as a pharmaceutical, drug substance, cosmetic, etc. In this specification, the terms "composition for drug delivery" and "drug delivery composition" are used interchangeably.

[0023] Biopolymer The drug delivery composition according to the present invention requires a minimal amount of biopolymer. As used herein, the term "biopolymer" means a natural polymer produced by the cells of a living body. Biopolymers consist of monomer units that covalently bond to form larger molecules. The present invention encompasses biopolymers of polypeptides, polysaccharides, and polynucleotides. Other examples of biopolymers include natural rubber (a polymer of isoprene), suberin and lignin (complex polyphenol polymers), cutin and cutan (complex polymers of long-chain fatty acids), and melanin. In an embodiment, the biopolymer used as a starting material and obtained in suspension is substantially pure, i.e., consists only of a purified natural polymer.

[0024] Preferably, the biopolymer used in the drug delivery composition is substantially free of chemical residues, i.e., no chemical residues are present, or are not detected or are present in trace amounts. Not detectable or present in trace amounts. As used herein, "substantially free of chemical residues" means that chemical compounds such as acids, bases, reactive chemicals, organic salts and / or inorganic salts, surfactants, dispersants (e.g., Tween 80 TM )), silanizing reagents, acrylamide, etc. are not present at all or are not detected or are present only in trace amounts in the final composition or final suspension. In an embodiment, the biopolymer constitutes at least 98 wt%, at least 99 wt%, at least 99.9 wt%, or at least 99.99 wt% of the organic compounds in the biopolymer composition or suspension, i.e., the biopolymer composition or suspension contains less than 2 wt%, less than 1 wt%, less than 0.1 wt%, less than 0.01 wt%, or less than 0.001 wt% of organic components other than the biopolymer or degradation products.

[0025] In an embodiment, the biopolymer comprises or consists of biopolymer molecules that have been mechanically treated into a stable, homogeneous aqueous suspension (e.g., a suspension of insoluble and / or semi-soluble biopolymer particles stably dispersed in a polar solvent).

[0026] In the present invention, the biopolymer may be insoluble or semi-soluble in water. As used herein, the term "insoluble biopolymer" means a biopolymer that is "insoluble" in a polar solvent (especially water), and this term encompasses equivalent terms such as "non-water-soluble", or "not soluble in water", or "water-insoluble", or "indissoluble". Insolubility can typically be observed by separation, i.e., by a precipitate / deposit of the biopolymer that is in a separate phase in an aqueous mixture, e.g., at the bottom or floating on top of the aqueous mixture. In the present invention, examples of insoluble biopolymers include, but are not limited to, chitin, chitosan, cellulose, hemicellulose, lignin, amylose, actin, fibrin, collagen, silk, fibroin, keratin, wool, alginic acid, and mixtures thereof. As used herein, the term "semi-soluble biopolymer" means a biopolymer that can be solubilized in a polar solvent such as water, but only under specific conditions (e.g., addition of chemicals such as molecular weight, heat, acid, alcohol, surfactant, etc.). In the present invention, examples of semi-soluble biopolymers include, but are not limited to, gelatin, pectin, starch, amylopectin, agarose, hyaluronic acid, RNA, DNA, xanthan gum, latex, polymannan, suberin, cutin, cutan, and mixtures thereof.

[0027] In an embodiment, the insoluble biopolymer is selected from chitin, chitosan, cellulose, hemicellulose, lignin, amylose, actin, fibrin, collagen, silk, fibroin, keratin, wool, and mixtures thereof. In an embodiment, the semi-soluble biopolymer is selected from gelatin, pectin, starch, amylopectin, agarose, alginic acid, alginate, hyaluronic acid, RNA, DNA, xanthan gum, guar gum, carrageenan, latex, polymannan, suberin, cutin, cutan, and mixtures thereof.

[0028] Sources of various biopolymers can be used and the present invention is not limited to a specific source. For example, suitable sources of chitin include, but are not limited to, green plants, algae, and fungi. Suitable sources of chitin and chitosan include, but are not limited to, fungi, crustaceans (e.g., crabs and shrimp), and insects. In an embodiment, the insoluble or semi-soluble biopolymer is obtained from fungi and mushrooms. In an embodiment, the insoluble or semi-soluble biopolymer is obtained from plant materials including, but not limited to, roots, tubers, leaves, petals, seeds, fruits, etc. Preferred sources are non-animal sources.

[0029] In an embodiment, the biopolymer is 100% natural biopolymer, e.g., SunSpheres Bio TM (microcrystalline cellulose, Dow Chemical), Chemjac TM (amorphophallus konjac root extract and xanthan gum, Chemspire), Kelset TM (sodium alginate, Dupont), Instant Pure-Flo F TM (corn starch, Ingredion), Gelcarin TM GP 379 (carrageenan, iota form, Dupont), Betafib TMMCF (cellulose (and) water-microfibrillated cellulose, Cosun Biobased Products), Betafib TM ETD (cellulose and cellulose gum-microfibrillated cellulose, Cosun Biobased Products), Exilva TM FM02-V,L (cellulose-microfibrillated cellulose, Borregard), Naturesoft TM 800 (cellulose fine powder), Kelcogel TM CG-HA (gellan gum-CP, Kelco), agar agar, and agarose, mushroom chitosan (e.g., GBS003, Qingdao Chibio Biotech), fungal chitosan (e.g., GBS010, Qingdao Chibio Biotech; or from Kraeber & Co), fungus-derived chitosan (e.g., Kiosmetine-CS TM , Kitozyme).

[0030] In an embodiment, the biopolymer is a naturally-derived biopolymer, such as, Natrathix TM biocellulose (cellulose gum, Ashland), Aquasorb TM A500 (cellulose gum, Ashland), Polysurf TM CS 67 / Natrosol TM CS plus 330 (cetyl hydroxyethyl cellulose, Ashland), Structure XL TM (hydroxypropyl starch phosphate, Nouryon), CD-58 (chitosan succinimide, Onlystar Bio-Technology Ltd), carboxymethyl chitosan derivative (GBS010, Qingdao Chibio Biotech), Makimousse TM 7 / 400 (sodium polyacrylate starch - kobo products, Daito Kasei Kogyo), Salanjul / Sanfresh TM1000 / 300sp (sodium polyacrylate starch, Iwase Cosfa USA Inc. / Sanyo), Antaron ECoT ethyl cellulose (ethyl cellulose, Ashland).

[0031] In an embodiment, the biopolymer is Chemjac TM (amorphophallus konjac root extract and xanthan gum, Chemspire), PemuPur TM start (microcrystalline cellulose (and) Sphingomonas fermentation extract (and) cellulose gum, Lubrizol), Nomcort CG (xanthan gum, ceratonia siliqua gum, Ikeda), and other synergistic combinations of biopolymers.

[0032] The biopolymer may also contain other biopolymer active substances such as B-CAN TM 55% (oat beta-glucan, Adams Food Ingredients) and / or mushroom-derived beta-glucan.

[0033] The present invention encompasses mixtures of two, three, four, five or more insoluble biopolymers including, but not limited to, chitin + chitosan, chitin + cellulose, chitin + collagen, chitin + silk, chitosan + silk, chitosan + cellulose, chitosan + collagen, cellulose + collagen, cellulose + silk, collagen + silk, etc. The present invention also encompasses mixtures of two, three, four, five or more semi-soluble biopolymers including, but not limited to, agarose + DNA, xanthan gum + starch, latex + alginate, xanthan gum + DNA, guar gum + cutan, etc. Also contemplated is the mixing of two, three, four, five or more insoluble and semi-soluble biopolymers including, but not limited to, chitin + agarose, chitosan + agarose, chitin + gelatin, chitin + xanthan gum, chitosan + xanthan gum, chitin + sodium hyaluronate, chitosan + sodium hyaluronate, cellulose + sodium hyaluronate, chitin + agarose, chitosan + agarose, cellulose + agarose.

[0034] The present invention also encompasses combinations of hydrophobically modified biopolymers and unmodified biopolymers that are capable of forming water-in-oil emulsions with stable viscosities when dispersed using high shear treatment and / or mechanical energy (regardless of the presence or absence of emulsifiers). Examples of hydrophobically modified biopolymers include Natrosol TM CS Plus 330 / Polysurf TM CS 67 (cetyl hydroxyethyl cellulose, Ashland), StarDesign Ultra TM (sodium starch octenyl succinate, Cargill Beauty), Inutec TM SP1 (inulin lauryl carbamate, Beneo), Texturlux Stabil TM (hydrolyzed corn starch hydroxyethyl ether, Primient).

[0035] In an embodiment, the biopolymer consists of a biopolymer composition containing biopolymer molecules mechanically treated into a stable homogeneous aqueous biopolymer suspension. As used herein, the term "homogeneous" generally means the appearance of the suspension to the naked eye (e.g., uniform color, uniform texture, etc.). "Homogeneous" as used herein does not exclude the possibility that the suspension is "heterogeneous" at the molecular level (e.g., various particle sizes, presence of aggregates, etc.). As used herein, the term "stable homogeneous aqueous biopolymer suspension", or similar terms that may be used interchangeably herein such as "homogeneous biopolymer suspension" or "stable biopolymer suspension" or simply "biopolymer suspension", all mean a suspension of insoluble and / or semi-soluble biopolymer particles stably dispersed in a polar solvent. The polar solvent is a polar protic solvent or a polar aprotic solvent. The polar solvent may be an aqueous solvent. The insoluble and / or semi-soluble biopolymer particles present in the biopolymer suspension may be in the shape of fibers and / or in the shape of aggregated spheres or aggregates. The stability of the biopolymer suspension can be evaluated by any suitable means. In a preferred embodiment, the stability is measured or observed by the absence of separation, i.e., the absence of a precipitate / deposit of biopolymer at the bottom or floating on top of the aqueous mixture, instead of two distinct phases in the aqueous mixture. Preferably, the biopolymer suspension according to the present invention is stable for at least 1 day, or at least 1 week, or at least 1 month, or at least 1 year or more (e.g., without separation).

[0036] Notwithstanding the above, one of ordinary skill in the art understands that insoluble and / or semi-soluble biopolymers never truly become soluble. Instead, they become "swellable" and bind to water. This is the reason why biopolymers become viscous suspensions in the high shear conditions and / or mechanical energy in which the biopolymers are provided in the present invention. Thus, the present invention encompasses both "swellable biopolymers" and "non-swellable biopolymers" because non-swellable polymers can be made swellable using high shear and / or mechanical energy. As used herein, a swellable biopolymer includes a biopolymer that absorbs and binds water, resulting in an increase in particle size and aqueous dispersion viscosity.

[0037] In an embodiment, the biopolymer becomes swellable by wet ball milling. This can include, but is not limited to, chitin, chitosan, hemicellulose, and alpha-corn starch.

[0038] In an embodiment, the biopolymer becomes swellable by high shear processing other than ball milling. This can include, but is not limited to, microcrystalline cellulose, microfibrillated cellulose, nanocellulose, hairy nanocellulose, konjac glucomannan, hydroxypropyl phosphate starch, high acyl type gellan gum, gellan gum, carboxymethyl starch, carboxymethyl cellulose (low ds type), agar agar, and agarose.

[0039] In the present invention, it is also conceivable to use soluble biopolymers including, but not limited to, xanthan gum, diutan gum, sodium alginate, and sclerotium gum.

[0040] In an embodiment, the biopolymer molecules or particles that are part of the drug delivery composition are mechanically treated to form a stable homogeneous aqueous biopolymer suspension. In an embodiment, the mechanical treatment involves high shear conditions and / or high mechanical energy. In an embodiment, the high shear conditions and / or high mechanical energy are obtained by a process including, but not limited to, mechanical shearing, shear thinning, planetary ball milling, rolling mill, vibration ball milling, tumbling stirred ball milling, horizontal media mill, colloid milling. As shown below, the high shear conditions and / or high mechanical energy can be applied for a certain time, with parameters, under appropriate conditions, until desired state changes are obtained, such as color change, viscosity change, change from slurry to paste, ointment, cream, lotion, gel or milk, etc.

[0041] Without wishing to be bound by theory, subjecting the biopolymer to high shear conditions and / or high mechanical energy improves the performance of the biopolymer, such as improvement in rheological properties such as viscosity, shear thinning properties and high yield value, which were not seen in conventional processes. The biopolymer dispersed using high shear treatment may include a lamellar crystalline gel network (LGN) that can synergistically increase the viscosity of the biopolymer dispersion. The oil + water biopolymer dispersion according to the present invention may include a Pickering emulsion in which an oil-in-water or water-in-oil emulsion is stabilized by the biopolymer.

[0042] In an embodiment, high shear conditions and / or high mechanical energy are achieved using suitable apparatus or instruments including, but not limited to, ball mills (e.g., planetary ball mills, rolling mills, vibrating ball mills, tumbling stirred ball mills, horizontal media mills, colloid mills, magnetic mills), twin screw extruders, high pressure homogenizers, blade homogenizers, stirring homogenizers, dispersers, rotor stator homogenizers, high shear mixers, plowshare mixers, dynamic mixers, plow mixers, turbine mixers, speed mixers, attrition millers, ultrasonic processors (e.g., high shear ultrasonication), tissue tearors, celllizers, polytrons, ribbon agitators, microfluidizers, high pressure homogenizers, and combinations thereof. In a preferred embodiment, the present invention utilizes ball milling under wet conditions. Specific examples of ball mills include vertical planetary mills (e.g., Tencan XQM-2A with a 100 mL zirconia jar and 10 mm diameter zirconia balls TM ), Flacktek with a 40 mL zirconia jar equipped with 5 mm diameter zirconia balls or zirconia rings TM Speed mixer (DAC 330-11 SE), 1.5L Supermill Plus equipped with 1.4 - 1.7 mm zirconia beads TM , and Netzsch mill Labstar equipped with 0.6 - 0.8 mm beads or 1.4 - 1.7 mm beads TM , but are not limited thereto.

[0043] In certain embodiments, the biopolymer compositions and suspensions according to the present invention are obtained using a specific protocol herein referred to as the "10 + 1 Alt method". This method involves grinding the biopolymer for a certain period of time (e.g., 10 minutes), followed by a short rest period (e.g., 1 minute), then a certain period of time (e.g., 10 minutes), for a total of 1 hour, or 2 hours, or 3 hours, or 5 hours, 10 hours, or 12 hours, grinding in the reverse direction.

[0044] Advantageously, the viscosity of the composition / suspension can be varied by changing the high shear conditions and / or mechanical energy to which the biopolymer is subjected. These conditions can be adjusted to obtain a stable homogeneous suspension (e.g., a stable colloidal homogeneous suspension) having the desired viscosity. Typically, supplying more mechanical energy increases shear and, correspondingly, decreases the viscosity of the final product. The biopolymer itself and / or the final composition for drug delivery can be formulated as a paste, ointment, cream, lotion, gel or milk.

[0045] In an embodiment, the biopolymer, and / or the biopolymer composition comprising biopolymer molecules or particles, is a colloidal homogeneous biopolymer suspension. In an embodiment, the colloidal homogeneous suspension comprises colloids having a range of from about 1 nm to about 1 μm.

[0046] In an embodiment, the biopolymer, and / or the biopolymer composition comprising biopolymer molecules, comprises biopolymer fibers. In an embodiment, the fibers have a width in the range of from about 1 nm to about 5 μm, or from about 5 nm to about 5 μm, from about 7 nm to about 5 μm, or from about 10 nm to about 5 μm, or from about 20 nm to about 5 μm, or from about 25 nm to about 5 μm, or from about 30 nm to about 5 μm, or from about 35 nm to about 5 μm, or from about 35 nm to about 3 μm. In an embodiment, the fibers have a width of at least 1 nm, or at least 5 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 75 nm, or at least 100 nm, or at least 250 nm, or at least 500 nm, or at least 750 nm, or at least 1 μm, or at least 2 μm, or at least 3 μm, or at least 4 μm, or at least 5 μm, or wider.

[0047] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules, comprises biopolymer fibers having a length of about 1 nm to about 200 μm, about 10 nm to about 100 μm, or about 50 nm to about 10 μm, or about 100 nm to about 10 μm, or about 500 nm to about 10 μm, or about 750 nm to about 10 μm, or about 800 nm to about 10 μm, or about 900 nm to about 5 μm, or about 1 μm to about 10 μm, or about 1 μm to about 5 μm, or about 1 μm to about 3 μm. In an embodiment, the fibers have a length of at least 1 nm, or at least 10 nm, at least 50 nm, or at least 100 nm, or at least 250 nm or at least 500 nm, or at least 750 nm, or at least 800 nm, or at least about 900 nm, or at least 1 μm, or at least 2 μm, or at least 3 μm, or at least 4 μm, or at least 5 μm, or at least 6 μm, or at least 7 μm, or at least 8 μm, or at least 9 μm, or at least 10 μm, or at least 25 μm, or at least 50 μm, or at least 75 μm, or at least 100 μm, or at least 150 μm, or at least 200 μm or longer. In an embodiment, the dry particle size range can be from about 1 nm to about 1 μm, or up to 10 μm, and the wet particle size range can be from about 200 nm to about 20 μm, or up to 200 μm.

[0048] In an embodiment, a biopolymer composition comprising a biopolymer and / or a biopolymer molecule comprises biopolymer fibers having both of the following: (i) a width greater than 20 nm (e.g., at least 25 nm, or at least 40 nm, or at least 50 nm) and a length greater than 50 nm (e.g., at least 100 nm, or at least 500 nm, or at least 1 μm, or at least 2 μm); or (ii) a width greater than 32 nm (e.g., at least 35 nm, or at least 40 nm, or at least 50 nm) and a length greater than 50 nm (e.g., at least 100 nm, or at least 500 nm, or at least 1 μm, or at least 2 μm); or (iii) a width greater than 20 nm (e.g., at least 25 nm, or at least 40 nm, or at least 50 nm) and a length greater than 500 nm (e.g., at least 600 nm, or at least 750 nm, or at least 1 μm, or at least 2 μm); or (iv) a width greater than 30 nm (e.g., at least 35 nm, or at least 40 nm, or at least 50 nm) and a length greater than 800 nm (e.g., at least 900 nm, or at least 1 μm, or at least 2 μm); or, (v) a width greater than 8 nm (e.g., at least 10 nm, at least 25 nm, or at least 35 nm, or at least 40 nm, or at least 50 nm) and a length greater than 340 nm (e.g., at least 350 nm, or at least 500 nm, at least 750 nm, or at least 900 nm, or at least 1 μm, or at least 2 μm); or, (vi) a width greater than 11 nm (e.g., at least 15 nm, at least 25 nm, or at least 35 nm, or at least 40 nm, or at least 50 nm) and a length greater than 166 nm (e.g., at least 200 nm, or at least 350 nm, or at least 500 nm, at least 750 nm, or at least 900 nm, or at least 1 μm, or at least 2 μm);or (viii) a width greater than 32 nm (e.g., at least 35 nm, or at least 40 nm, or at least 50 nm) and a length greater than 800 nm (e.g., at least 900 nm, or at least 1 μm, or at least 2 μm, or at least 3 μm, or at least 4 μm, or at least 5 μm, or at least 6 μm, or at least 7 μm, or at least 8 μm, or at least 9 μm, or at least 10 μm, or at least 25 μm, or at least 50 μm, or at least 75 μm, or at least 100 μm, or at least 150 μm, or at least 200 μm or longer).;

[0049] In an embodiment, a biopolymer, and / or a biopolymer composition containing biopolymer molecules, is a biopolymer fiber, wherein the average width and average length of the fibers in the composition are as defined above in this specification, e.g., an average width greater than 20 nm (e.g., at least 25 nm, or at least 40 nm, or at least 50 nm) and an average length greater than 50 nm (e.g., at least 60 nm, at least 75 nm, or at least 100 nm, or at least 500 nm, at least 750 nm, or at least 1 μm, or at least 2 μm, or at least 3 μm, or at least 4 μm, or at least 5 μm, or at least 6 μm, or at least 7 μm, or at least 8 μm, or at least 9 μm, or at least 10 μm, or at least 25 μm, or at least 50 μm, or at least 75 μm, or at least 100 μm, or at least 150 μm, or at least 200 μm or longer) of biopolymer fibers.

[0050] In an embodiment, a biopolymer suspension and / or a biopolymer composition containing biopolymer molecules has a pH of about 6.5 to about 8.5. In a particular embodiment, the biopolymer suspension is a chitosan suspension having a pH of about 7.8 to about 8.1.

[0051] In an embodiment, a biopolymer composition comprising a biopolymer and / or a biopolymer molecule includes biopolymer fibers having both crystalline regions and amorphous regions. In an embodiment, a stable homogeneous suspension includes spherical biopolymer fibers. In an embodiment, a stable homogeneous suspension consists mainly of, or consists only of, suspended biopolymer nanofibrils.

[0052] Those skilled in the art recognize that particle size measurements can vary depending on the measurement method and the state of the particles (e.g., wet particles are generally larger than the same particles in a dry state). Typically, when measured by dynamic light scattering (DLS), the particles are in a wet or suspended state, and when measured by scanning electron microscopy (SEM), the particles are in a dry state.

[0053] In an embodiment, a biopolymer composition comprising a biopolymer and / or a biopolymer molecule includes alginate agglomerated spheres having an average size of about 40 nm to about 80 nm, or about 45 nm to about 75 nm, as measured by scanning electron microscopy (SEM). In an embodiment, a stable homogeneous suspension includes alginate agglomerated spheres having a median size of about 30 nm to about 70 nm, or about 35 nm to about 65 nm, and an average size of about 40 nm to about 80 nm, or about 45 nm to about 75 nm, as measured by scanning electron microscopy (SEM).

[0054] In an embodiment, a biopolymer composition comprising a biopolymer and / or a biopolymer molecule includes cellulose agglomerated spheres having an average size of about 50 nm to about 80 nm, or about 55 nm to about 75 nm, about 40 nm to about 80 nm, or about 45 nm to about 75 nm, as measured by scanning electron microscopy (SEM). In an embodiment, a stable homogeneous biopolymer suspension includes cellulose agglomerated spheres having a median size of about 35 nm to about 75 nm, or about 40 nm to about 65 nm, and an average size of about 40 nm to about 80 nm, or about 45 nm to about 75 nm, as measured by scanning electron microscopy (SEM).

[0055] In an embodiment, a biopolymer composition comprising a biopolymer and / or biopolymer molecules comprises aggregated spheres of chitin having an average size of about 45 nm to about 85 nm, or about 50 nm to about 80 nm. In an embodiment, a stable homogeneous biopolymer suspension comprises aggregated spheres of cellulose having a central size of about 45 nm to about 80 nm, or about 50 nm to about 75 nm as measured by scanning electron microscopy (SEM).

[0056] In an embodiment, a biopolymer composition comprising a biopolymer and / or biopolymer molecules comprises aggregated spheres of chitosan having an average size of about 75 nm to about 120 nm, or about 80 nm to about 115 nm, or about 85 nm to about 110 nm as measured by scanning electron microscopy (SEM). In an embodiment, a stable homogeneous suspension comprises aggregated spheres of chitosan having a central size of about 70 nm to about 100 nm or about 75 nm to about 95 nm as measured by scanning electron microscopy (SEM).

[0057] In an embodiment, a biopolymer composition comprising a biopolymer and / or biopolymer molecules comprises aggregated spheres of silk having an average size of about 40 nm to about 165 nm, or about 45 nm to about 160 nm as measured by scanning electron microscopy (SEM). In an embodiment, a stable homogeneous biopolymer suspension comprises aggregated spheres of silk having a central size of about 40 nm to about 150 nm or about 45 nm to about 140 nm as measured by scanning electron microscopy (SEM).

[0058] In an embodiment, a biopolymer composition comprising a biopolymer and / or biopolymer molecules comprises one or more particles of alginic acid, cellulose, chitin, chitosan, and silk, and the range of particle sizes measured by SEM is as defined in the tables and figures of WO 2022 / 137184.

[0059] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules is characterized by the visual properties depicted in the SEM images shown in the figures of WO2022 / 137184.

[0060] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules is characterized by the Fourier transform infrared spectroscopy (FTIR) spectrum depicted in the figures of WO 2022 / 137184.

[0061] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules is characterized by the solid-state nuclear magnetic resonance property evaluation (SSNMR) depicted in the figures of WO2022 / 137184.

[0062] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules is characterized by the powder X-ray diffraction (PXRD) pattern(s) depicted in the figures of WO 2022 / 137184.

[0063] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules is characterized by the dynamic light scattering (DLS) measurements reported in WO 2022 / 137184.

[0064] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules is characterized by the transmittance spectrum shown in the figures of WO2022 / 137184.

[0065] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules is characterized by the sweep suspension test reported in WO 2022 / 137184.

[0066] In an embodiment, a biopolymer, and / or a biopolymer composition comprising biopolymer molecules, is characterized by the rheological behavior depicted in the figures of WO 2022 / 137184.

[0067] Pharmaceutical Active Ingredient The present invention particularly aims to provide a vehicle for transporting, delivering and / or releasing a compound of interest.

[0068] In an embodiment, the compound of interest is a "pharmaceutical active ingredient" or "API". As used herein, the term pharmaceutical active ingredient or API encompasses any substance or compound that can provide at least one beneficial health benefit to a subject. For example, the API may be a cosmetic compound, a pharmaceutical compound, or a drug substance, etc.

[0069] As used herein, the term "subject" includes a living body to which delivery of the compound of interest is desired. The term "subject" includes animals (e.g., mammals (e.g., cats, dogs, horses, pigs, cows, goats, sheep, rodents (e.g., mice or rats), rabbits, squirrels, bears, primates (e.g., chimpanzees, monkeys, gorillas and humans)), as well as birds (e.g., chickens, ducks, Pekin ducks, geese), and their transgenic species. Preferably, the subject is a human or a non-human primate (e.g., chimpanzee, monkey, macaque, gorilla). More preferably, the subject is a human. Even more preferably, the subject is a human in need of treatment and having or potentially having one or more undesirable health problems and / or symptoms. In an embodiment, the subject is a human who may benefit from the delivery and release of a pharmaceutical formulation of a cosmetic, for example onto its skin or a layer thereof.

[0070] A pharmaceutical compound can be any compound having pharmaceutical activity, including but not limited to analgesics, anesthetics, antidotes, antibacterial agents, antispasmodics, anti-dementia agents, antidepressants, antiemetics, antifungal agents, antigout agents, anti-inflammatory drugs, anti-migraine agents, anti-myasthenic agents, anti-mycobacterial drugs, anti-cancer drugs, anti-obesity agents, antiparasitics, antiparkinson agents, antipsychotics, antispasticity agents, antiviral agents, anxiolytics, bipolar agents, blood glucose regulators, blood products, cardiovascular drugs, central nervous system drugs, contraceptives, dental and oral agents, topical agents, electrolytes, minerals, metals, vitamins, gastrointestinal agents, genitourinary agents, adrenal hormones, pituitary hormones, prostaglandin hormones, sex hormones, thyroid hormones, adrenal hormone suppressants, pituitary hormone suppressants, thyroid hormone suppressants, immunological agents, infertility agents, inflammatory bowel disease agents, metabolic bone disease agents, ophthalmic agents, otic agents, respiratory tract agents, sexual disorder agents, skeletal muscle relaxants, sleep disorder agents.

[0071] In an embodiment, the pharmaceutical compound is acetaminophen, acetylsalicylic acid, acyclovir, acrivastine, adalimumab, alendronic acid, allopurinol, alogliptin, amitriptyline for depression, amitriptyline for pain / migraine, amlodipine, amoxicillin, anastrozole, apixaban, atenolol, atorvastatin, azathioprine, azithromycin, baclofen, beclomethasone inhaler, beclomethasone nasal spray, beclomethasone skin cream, bendroflumethiazide, benzoyl peroxide, benzydamine, betahistine, betamethasone for eyes / ears / nose, betamethasone for skin, bimatoprost, bisacodyl, bisoprolol, brinzolamide, budesonide inhaler, budesonide nasal spray, budesonide rectal foam and enema, bumetanide, buprenorphine for pain, buscopan (hyoscine butylbromide), candesartan, carbamazepine, carbimazole, carbocysteine, carmellose sodium, carvedilol, cephalexin, cetirizine, varenicline, chloramphenicol, chlorhexidine, chlorphenamine, cinarizine, ciprofloxacin, citalopram, clarithromycin, clobetasol, clobetasone, clonazepam, clopidogrel, clotrimazole, clotrimazole, co-amoxiclav, co-beneldopa, co-careldopa, co-codamol for adults, co-codamol for children, co-codaprin (aspirin and codeine), co-dydramol, codeine, colchicine, cyanocobalamin, cyclizine, dabigatran, dapagliflozin, dexamethasone tablets and dexamethasone solution, diazepam, diclofenac, digoxin, dihydrocodeine, diltiazem, diphenhydramine, dipyridamole, doxart, domperidone, donepezil, dosulepin, doxazosin, doxycycline, duloxetine, edoxaban, empagliflozin, enalapril, eplerenone, erythromycin, escitalopram, esomeprazole, ezetimibe, felodipine, fentanyl, ferrous fumarate, ferrous sulfate,Fexofenadine, Finasteride, Flucroxycillin, Fluconazole, Fluoxetine, Fluticasone inhaler, Fluticasone nasal spray and drops, Fluticasone skin cream, Folic acid, Furosemide, Fusidic acid, Fybogel (ispaghula husk), Gabapentin, Glibenclamide, Glimepiride, Glyceryl trinitrate, Heparinoid, Hydrocortisone, Hydrocortisone buccal tablets, Hydrocortisone for haemorrhoids and anal itching, Hydrocortisone for skin, Hydrocortisone injection, Hydrocortisone rectal foam, Hydrocortisone tablets, Hydroxocobalamin, Hyoscine hydrobromide, Ibuprofen, Indapamide, Irbesartan, Isosorbide mononitrate, Isosorbide dinitrate, Isotretinoin capsules, Isotretinoin gel, Ketoconazole, Labetalol, Lactulose, Lamotrigine, Lansoprazole, Latanoprost, Lercanidipine, Letrozole, Levetiracetam, Levothyroxine, Lidocaine, Linagliptin, Lisinopril, Lithium, Loperamide, Loratadine, Lorazepam, Losartan, Low-dose aspirin, Lomecycline, Macrogol, Mebendazole, Mebeverine, Melatonin, Mesalazine, Metformin, Methadone, Methotrexate, Methylphenidate, Metoclopramide, Metoprolol, Metronidazole, Mirabegron, Mirtazapine, Molnupiravir, Mometasone, Montelukast, Morphine, Naproxen, Nepafenac, Nicorandil, Nifedipine, Nitrofurantoin, Nortriptyline, Nystatin, Olanzapine, Olmesartan, Omeprazole, Oxybutynin, Oxycodone, Pantoprazole, Paroxetine, Nirmatrelvir, Peppermint oil, Perindopril, Phenoxymethylpenicillin, Phenytoin, Pioglitazone, Pravastatin, Prednisolone tablets and prednisolone liquid, Pregabalin, Prochlorperazine, Promethazine, Propranolol, Pseudoephedrine, Rabeprazole, Ramipril, Ranitidine, Remdesivir, Risedronate, Risperidone, Rivaroxaban, Ropinirole, Rosuvastatin, Salbutamol inhaler, Saxagliptin, Senna, Sertraline, Sildenafil,It is selected from simeticone, simvastatin, sitagliptin, sodium valproate, solifenacin, sotalol, sotrovimab, sulfasalazine, sumatriptan, tadalafil, tamsulosin, temazepam, terbinafine, thiamine (vitamin B1), ticagrelor, trosildenafil, topiramate, tramadol, tranexamic acid, trazodone, trimethoprim, valproic acid, valsartan, varenicline, venlafaxine, verapamil, zolpidem and zopiclone.,

[0072] In an embodiment, the pharmaceutical compound is used for acne, acute cholecystitis, acute lymphoblastic leukemia, acute myeloid leukemia, acute pancreatitis, Addison's disease, alcohol-related liver disease, allergic rhinitis, allergy, Alzheimer's disease, anal cancer, Anaphylaxis, angioedema, ankylosing spondylitis, anxiety, anxiety disorder, appendicitis, arthritis, asthma, atopic eczema, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bacterial vaginitis, benign prostatic hyperplasia, cholangiocarcinoma (cholangiocellular carcinoma), overeating, bipolar disorder, bladder cancer, sepsis (pyemia), bone cancer, bowel cancer, fecal incontinence, intestinal polyps, brain tumor, breast cancer, bronchiectasis, bronchitis, bulimia nervosa, warts, carcinoid syndrome and carcinoid tumor, Catarrh, cellulitis, cervical cancer, chest infection, chest pain, chickenpox, chilblains, Chlamydia, chronic fatigue syndrome, chronic kidney disease, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic obstructive pulmonary disease, chronic pancreatitis, cirrhosis, Clostridium difficile, celiac disease, herpes simplex, coma, common cold, Common heart condition, congenital heart disease, conjunctivitis, constipation, Coronavirus (COVID-19), cough, Crohn's disease, croup, cystic fibrosis, cystitis, hydrocele, deep vein thrombosis, dehydration, dementia, Lewy body dementia, dental abscess, depression, dermatitis herpetiformis, diabetes, diarrhea, nummular eczema, diverticular disease and diverticulitis, dizziness (faintness), Down syndrome, dry mouth, dysphagia (swallowing disorder), dystonia, earache, earwax buildup, Ebola virus disease, ectopic pregnancy, endometriosis, epilepsy, erectile dysfunction (impotence), Escherichia coli (E.coli) O157, Ewing sarcoma, Ewing sarcoma: children, eye cancer, febrile convulsions, adult fever, child fever, uterine fibroids, fibromyalgia, flatulence, influenza, fetal alcohol syndrome, food poisoning, Fungal nail infection, gallbladder cancer, gallstones, ganglion cysts, gastroenteritis, gastroesophageal reflux disease (GORD), genital herpes, genital warts, germ cell tumor, glandular fever, gonorrhea, gout, periodontal disease, hemorrhoids (piles), hairy cell leukemia, hand, foot and mouth disease, hay fever, head and neck cancer, head lice andnits), headache, hearing loss, heart failure, hepatitis A, hepatitis B, hepatitis C, hiatal hernia, high cholesterol, HIV, Hodgkin lymphoma, Hodgkin lymphoma: children, Hodgkin lymphoma: teenagers / young adults, Huntington's disease, hyperglycemia (high blood sugar), hyperhidrosis, hypoglycemia (low blood sugar), idiopathic pulmonary fibrosis, impetigo, indigestion, ingrown toenails, inherited heart condition, insomnia, iron deficiency anemia, irritable bowel syndrome (IBS), irritable hip, itching, itchy bottom, Kaposi's sarcoma, kidney cancer, kidney infection, kidney stones, labyrinthitis, lactose intolerance, Langerhans cell histiocytosis, laryngeal (larynx) cancer, laryngitis, lower limb cramps, lichen planus, liver cancer, liver disease, liver tumor, loss of libido, lung cancer, lupus, Lyme disease, lymphoedema, lymphogranuloma venereum (LGV), malaria, malignant brain tumor (cancerous), malnutrition, measles, meningitis, menopause, mesothelioma, middle ear infection (otitis media), migraine, motor neuron disease (MND), mouth cancer, mouth ulcers, multiple myeloma, multiple sclerosis (MS), mumps, Ménière's disease, nasal / sinus cancer, nasopharyngeal cancer, neuroblastoma, neuroendocrine tumor, non-alcoholic fatty liver disease (NAFLD), non-Hodgkin lymphoma, non-Hodgkin lymphoma: children, norovirus, nosebleeds, obesity, obsessive-compulsive disorder (OCD), obstructive sleep apnea, oesophageal cancer, oral thrush in adults, osteoarthritis, osteoporosis, osteosarcoma, otitis externa, ovarian cancer, ovarian cancer: teenagers / young adults, ovarian cysts, overactive thyroid, Paget's disease of the nipple, pancreatic cancer, panic disorder, Parkinson's disease, pelvic inflammatory disease, pelvic organ prolapse, penile cancer, peripheral neuropathy, personality disorder, pleurisy, pneumonia, polymyalgia rheumatica, post-traumatic stress disorder (PTSD), postnatal depression, pregnancy and baby, pressure sores, prostate cancer, psoriasis, psoriatic arthritis, psychosis, pubic lice, rare tumors, Raynaud's symptoms, reactive arthritis, restless legs syndrome, retinoblastoma, retinoblastoma: children, rhabdomyosarcoma, rheumatoid arthritis, ringworm and other fungal infections, scabies, scarlet fever, schizophrenia, scoliosis, septic shock, shingles, shortness of breath, sickle cell disease, sinusitis, Sjögren's syndrome, skin cancer (melanoma), skin cancer (non-melanoma), slapped cheek (infectious erythema)syndrome), soft tissue sarcoma, soft tissue sarcoma: teenagers and young adults, sore throat, spleen problems and splenectomy, stillbirth, stomach pain and abdominal pain, gastric cancer, gastric ulcer, stress, anxiety and depression, stroke, sudden infant death syndrome (SIDS), suicide, sunburn, swollen glands, syphilis, testicular cancer, testicular cancer: teenagers and young adults, testicular lump and swelling, thirst in the throat, threadworms, thrush, thyroid cancer, thyroid cancer, tinnitus, tonsillitis, wisdom teeth, toothache, transient ischemic attack (TIA), trigeminal neuralgia, tuberculosis (TB), type 1 diabetes, type 2 diabetes, trichomonas infection, ulcerative colitis, hypothyroidism, urinary incontinence, urinary tract infection (UTI), urinary tract infection (UTI) in children, urticaria (hives), vaginal cancer, vaginal thrush, varicose eczema, venous leg ulcer, dizziness, vitamin B12 or folic acid deficiency anemia, adult vomiting, vulvar cancer, wart and verruca, whooping cough, Wilms tumor, womb (uterus) cancer, yellow fever, and is a compound for use in the treatment and / or prevention of a medical condition selected from the group consisting of.

[0073] The API can be any compound useful in cosmetics including, but not limited to, a compound for moisturizing the skin, a compound for improving skin appearance, a compound for protecting against environmental damage, a compound for combating the effects of aging, a compound for removing wrinkles and / or sunspots, and / or a compound for preventing any of the following skin symptoms: Acne, acne / folliculitis, acne scars, skin aging, blemishes, broken blood vessels, brown spots or other discolored skin, cellulite, creases around the mouth or nose, deflated or sunken cheeks, temples, lips and around the eyes, dull discolored skin, thick facial or body hair, enlarged pores, tired or fatigued appearance, fine lines and wrinkles, rough cracked skin, flushed appearance, freckles on the forehead, furrows or wrinkles, hair loss, hair removal, hirsutism and hypertrichosis, hyperpigmentation, melasma, rosacea, sagging or loss of volume, skin scarring, skin cancer, spider veins on the legs and face, sun-damaged skin, sunspots, tattoo removal, texture and color changes, tiny lines near the eyes or mouth, visible facial blood vessels, wrinkles and fine lines, etc.

[0074] The API may also be any compound useful in hygiene products such as anti-acne products, toothpaste and anti-caries products, antiperspirants, astringents, corn and keratolytic agents, dandruff products, hair growth / hair removal products, nail clippers, and wart removers. The API may also be a compound useful in other skin products such as skin bleaching agents, sunscreens, topical analgesics, topical antifungals, antimicrobials, etc.

[0075] In an embodiment, the cosmetic compound is selected from antioxidants (e.g., resveratrol, vitamin C), alpha hydroxy acids (AHA), hyaluronic acid, retinoids (e.g., retinol), vitamins (e.g., vitamin A, vitamin E), resorcinol, benzoyl peroxide, salicylic acid, ceramides, niacinamide, sulfur, sodium fluoride, sodium monophosphate, clioquinol, haloprogin, miconazole nitrate, povidone-iodine, tolnaftate, undecylenic acid, calcium undecylenate, copper undecylenate, zinc undecylenate, clotrimazole bacitracin, chlortetracycline, neomycin sulfate, tetracycline hydrochloride, aluminum chloride, aluminum chlorohydrate, aluminum chlorohydrex polyethylene glycol, aluminum chlorohydrex propylene glycol, aluminum dichlorohydrate, aluminum dichlorohydrex polyethylene glycol, aluminum dichlorohydrex propylene glycol, aluminum sesquichlorohydrate, aluminum sesquichlorohydrex polyethylene glycol, aluminum sesquichlorohydrex propylene glycol, aluminum zirconium octachlorohydrate, aluminum zirconium octachlorohydrex gly, aluminum zirconium pentachlorohydrate, aluminum zirconium pentachlorohydrex gly, aluminum zirconium tetrachlorohydrate, aluminum zirconium tetrachlorohydrex gly, aluminum zirconium trichlorohydrate, aluminum zirconium trichlorohydrex gly, allantoin, aluminum hydroxide gel, calamine, cocoa butter, cod liver oil, dimethicone, glycerin, kaolin, lanolin, mineral oil, sodium bicarbonate, zinc acetate, zinc carbonate, zinc oxide, aluminum acetate, aluminum sulfate, witch hazel, selenium sulfide, zinc pyrithione, selenium sulfide, coal tar, hydroquinone, benzocaine, lidocaine.

[0076] Manufacture The drug delivery composition according to the present invention can be manufactured using any suitable method and conditions.

[0077] In an embodiment, obtaining the drug delivery composition involves mixing the API with stable homogeneous aqueous media containing insoluble and / or semi-soluble particles.

[0078] In an embodiment, the manufacture of the drug delivery composition involves mechanically treating the API and the biopolymer together under high shear conditions and / or high mechanical energy to obtain a stable homogeneous aqueous composition as defined herein, the composition containing insoluble and / or semi-soluble particles in which the API(s) is / are dispersed. Some examples of such manufacture are shown in the exemplary section below.

[0079] The drug delivery composition according to the present invention is preferably stable. By stability is meant, at least, that the biopolymer (e.g., fibers, spheres) or any other component of the composition does not sediment to the bottom. In an embodiment, the insoluble and / or semi-soluble biopolymer(s) is / are retained in suspension for at least one week, or at least one month, or at least six months, or at least twelve months, or at least eighteen months, or at least two years, or at least three years or more.

[0080] Preferably, the drug delivery composition according to the present invention also provides a stable environment for the API(s) contained in the composition. A person skilled in the art can readily identify and provide such a stable environment for the API, for example, by selecting a suitable biopolymer or combination thereof, identifying a suitable concentration or ratio for the biopolymer(s) and / or the API, and adding additional compounds (e.g., stabilizers, pH adjusters, binders, salts, cross-linking agents, co-solvents, plasticizers, etc.).

[0081] The pharmaceutical delivery composition according to the present invention can be formulated as a paste, ointment, cream, lotion, gel or emulsion. In an embodiment, the desired formulation is obtained by obtaining a composition having the desired viscosity. In an embodiment, the viscosity of the composition / suspension can be changed by changing the high shear conditions and / or mechanical energy to which the biopolymer(s) is / are subjected. In an embodiment, a stable homogeneous suspension has a viscosity of from about 25 mPa to about 85000 mPa. Table 1 below provides non-limiting examples of desirable viscosities of the composition / suspension according to the present invention.

[0082]

Table 1

[0083] In an embodiment, the viscosity of the pharmaceutical delivery composition according to the present invention can be changed by appropriately selecting the biopolymer contained in the composition and / or API.

[0084] The viscosity of the pharmaceutical delivery composition according to the present invention can be altered depending on the respective ratio or concentration of each of the compounds entering the composition, in addition to the biopolymer. In an embodiment, the weight ratio of biopolymer:API is from about 0.1:20 to about 10:20, or from about 0.5:20 to about 3:20, or about 0.75:20, or about 1.0:20, 1.25:20, or about 1.5:20.

[0085] In an embodiment, the drug delivery composition according to the present invention comprises about 0.01 to 10% w / w of a biopolymer, or 0.01 to 5% w / w of a biopolymer, or 0.01 to 2% w / w of a biopolymer, or 0.01 to 1% w / w of a biopolymer. In an embodiment, the composition according to the present invention comprises about 0.01% w / w of a biopolymer, or about 0.05% w / w of a biopolymer, or about 0.1% w / w of a biopolymer, or about 0.25% w / w of a biopolymer, or about 0.5% w / w of a biopolymer, or about 0.75% w / w of a biopolymer, or about 1% w / w of a biopolymer, or about 1.5% w / w of a biopolymer, or about 2.5% w / w of a biopolymer, or about 5% w / w of a biopolymer.

[0086] The drug delivery composition according to the present invention can also be formulated as a stable emulsion comprising a fatty acid (e.g., C10-C22 fatty acid), an oil and / or a wax, and / or N-acetylglucosamine, and / or an emulsifier and a preservative, and / or an additive (including but not limited to preservatives, stabilizers and emulsifiers). In an embodiment, the additive is selected from cetyl alcohol, glyceryl stearate, soybean butter, PC90, tara gum, PSC3, PEG, guar, xanthan gum, agarose, sodium hyaluronate, Tween 80 TM and glycerol. The additive(s) can be added before, during, or after combining the biopolymer and the API.

[0087] The drug delivery composition of the present invention can also be provided in a dry form and formulated as tablets, capsules, pellets, granules, films, transdermal patches, implants, scaffolds, suppositories, etc.

[0088] Delivery Methods and Related Uses The composition according to the present invention can find numerous applications in delivering the compound of interest (e.g., API) to a subject in need thereof.

[0089] In one aspect, the present invention relates to a method of delivering a pharmaceutical active ingredient (API) to a subject in need thereof. In one embodiment, the method comprises providing a composition as defined herein and administering the composition to the subject. The composition can be administered using any suitable route that enables delivery and release of the API at the desired site.

[0090] For example, the formulation can be manufactured to provide a composition formulated in a form suitable for any of the routes such as topical administration, oral administration, sublingual administration, buccal administration, rectal administration, intravaginal administration, intraocular administration, otic administration, nasal administration, dermal administration, and transdermal administration. In a preferred embodiment, the route of administration is topical administration or oral administration.

[0091] According to a particular aspect, the administration is topical administration and the present invention relates to a method for topical delivery. In one embodiment, the method comprises providing an aqueous composition comprising a biopolymer and at least one API, and topically applying the composition onto the subject's body.

[0092] The composition can be applied to any desired surface of the subject, including but not limited to the hands, arms, legs, feet, torso, chest, face, neck, scalp, etc. In an embodiment, the composition is applied to an area of the skin, including wounds, scars, wrinkles, and any other type of injury. For topical use, the composition can be formulated as a paste, ointment, cream, lotion, gel, or emulsion.

[0093] According to a particular aspect, the administration is oral administration and the present invention relates to a method for oral delivery. In one embodiment, the method comprises: (i) providing a mixture comprising an API mixed in a biopolymer composition; (ii) drying the mixture to obtain a dried product; and (iii) orally administering the dried product to the subject. For oral administration, the dried product can take the form of tablets, capsules, pellets, granules, etc. As other methods of administration, the dried product can take the form of films, transdermal patches, implants, scaffolds, suppositories, etc.

[0094] One skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims appended hereto. This invention is further illustrated by the following examples, which should not be construed as further limiting or in any way particularizing.

Example

[0095] In the present invention, experiments were conducted to demonstrate the release of small pharmaceutical molecules or APIs from the biopolymer composition.

[0096] A biopolymer suspension with a known amount of API added was easily prepared. Next, the suspension containing the API was dried to form pellets. Next, these pellets were added to a known amount of water, and aliquots of water were periodically removed to determine the release rate of the API. The concentration of the API was measured using UV / VIS spectroscopy.

[0097] Example 1: Acetaminophen in Chitin The acetaminophen - biopolymer suspension was produced by grinding 21.88 g of chitin suspension (1.05:20) and 0.50 g of acetaminophen with 50 units of 10 mm balls at 670 RPM using the 10 + 1 Alt method (a total grinding method of 2 hours, grinding for 10 minutes, then resting for 1 minute, and then grinding in the reverse direction for 10 minutes). The acetaminophen concentration in the resulting aqueous suspension was 2.23% w / w. In a 20 L batch, a 1.5 L Supermill Plus equipped with 1.4 - 1.7 mm zirconia beads TM was used to produce the chitin suspension by grinding with 982 mL of 1.4 - 1.7 mm zirconia beads under general grinding conditions of a pump flow rate of 7.3 GPH (gallons per hour) and a rotational speed of 2400 FPM (feet per minute), where 20 liters of slurry was treated at 5% solids (1.05:20).

[0098]

Table 2

[0099] The sample was dried in an oven at 50 °C for 3 hours and then in air for 10 hours. The acetaminophen concentration in the dried product was 29.58% w / w.

[0100] The acetaminophen - biopolymer suspension was successful in the release of acetaminophen as shown in Figure 1. This figure represents the release of acetaminophen from a chitin suspension doped with dry acetaminophen into water, where the concentration of acetaminophen (g / L) is plotted against time (minutes). As can be seen, most of the acetaminophen is released in the first 35 - 50 minutes and then slowly released over 23 hours. This suggests zero - order controlled release.

[0101] Example 2: Acetaminophen in Chitosan The acetaminophen - biopolymer suspension was produced by grinding 22.64 g of chitosan suspension (1.05:20) and 0.50 g of acetaminophen with 50 units of 10 mm balls at 670 RPM using the 10 + 1 Alt method (a total of 2 hours of grinding method where it is ground for 10 minutes, then rested for 1 minute, and then ground in the reverse direction for 10 minutes). The concentration of acetaminophen in the aqueous suspension thus obtained was 2.16% w / w. In a 20 L batch, a 1.5 L Supermill Plus equipped with 1.4 - 1.7 mm zirconia beads TM was used to produce the chitosan suspension by grinding with 982 mL of 1.4 - 1.7 mm zirconia beads at a pump flow rate of 7.3 GPH (gallons per hour) and a rotational speed of 2400 FPM (feet per minute) under general grinding conditions, where 20 liters of slurry was treated at 5% solids (1.05:20).

[0102]

Table 3

[0103] The sample was dried in an oven at 50 °C for 10 hours and then for 3 hours in air. The concentration of acetaminophen in the dried matter was 25.23% w / w.

[0104] As shown in Figure 2, the acetaminophen - biopolymer suspension was successful in the release of acetaminophen. This figure represents the release of acetaminophen from a chitosan suspension doped with dry acetaminophen into water, where the concentration of acetaminophen (g / L) is plotted against time (minutes). As can be seen, most of the acetaminophen was released in the first 35 - 50 minutes, and then it was released slowly over the next 23 hours. This suggests zero - order controlled release.

[0105] Example 3: Acetylsalicylic Acid in Chitosan The acetylsalicylic acid - biopolymer suspension was produced by grinding 22.09 g of chitosan and 0.50 g of acetylsalicylic acid using the 10 + 1 Alt method (a total grinding method of 2 hours, where it is ground for 10 minutes, then rested for 1 minute, and then ground in the reverse direction for 10 minutes) with 50 pieces of 10 - mm balls at 670 RPM. The concentration of acetylsalicylic acid in the aqueous suspension thus obtained was 2.21% w / w. In a 20 - L batch, a 1.5 - L Supermill Plus equipped with 1.4 - 1.7 mm zirconia beads TM was used to produce a chitosan suspension by grinding with 982 mL of 1.4 - 1.7 mm zirconia beads at a pump flow rate of 7.3 GPH (gallons per hour) and a rotational speed of 2400 FPM (feet per minute) under general grinding conditions, where 20 liters of slurry was treated at 5% solids (1.05:20).

[0106]

Table 4

[0107] The sample was dried in an oven at 50 °C for 10 hours and then for 3 hours in air. The acetylsalicylic acid concentration in the dried product was 34.99% w / w.

[0108] As shown in Figure 3, the acetylsalicylic acid - biopolymer suspension was successful in the release of acetaminophen. This figure represents the release of acetylsalicylic acid from the dry acetylsalicylic acid - doped chitosan suspension into water, with the concentration of acetylsalicylic acid (g / L) plotted against time (minutes). As can be seen, most of the acetylsalicylic acid was released in the first 35 - 50 minutes and then released slowly over 23 hours. This suggests zero - order controlled release.

[0109] Discussion Since both acetaminophen and acetylsalicylic acid were added to the biopolymer suspension and then released from the dry suspension later, this example demonstrates that the biopolymer composition according to the present invention can be successfully used for drug delivery.

[0110] Since the release of acetaminophen from the dry biopolymer matrix was slower than that of acetylsalicylic acid, this example also shows that the biopolymer suspension of the present invention is useful for controlling the release of different drugs.

[0111] In this regard, without wishing to be bound by theory, the particle size of the polymer may affect the release rate. Therefore, it would be possible to control the release rate of the desired API by changing the particle size of the polymer suspension.

[0112] Headings are provided herein to assist in referencing and identifying the location of particular sections. These headings are not intended to limit the scope of the concepts described therein, which may be applicable to other sections throughout this document. Accordingly, the present invention is not intended to be limited to the embodiments shown herein, but rather is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

[0113] The singular forms "a", "an", and "the" include corresponding plural references unless the context clearly dictates otherwise. Thus, for example, reference to "a biopolymer" includes one or more such biopolymers, and reference to "a method" includes reference to equivalent steps and methods known to those skilled in the art that can modify or substitute the methods described herein.

[0114] Unless otherwise indicated, all numbers expressing amounts of ingredients, reaction conditions, concentrations, properties, etc. used in the specification and claims are to be understood as being modified in all instances by the term "about". At a minimum, each numerical parameter should be construed in light of the reported significant digits and by applying ordinary rounding techniques. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the properties sought to be obtained. Although numerical ranges and parameters representing the broad scope of embodiments are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. However, any numerical value inherently contains certain errors resulting from variations in experiments, test measurements, statistical analyses, etc.

[0115] The examples and embodiments described herein are for illustrative purposes only, and various changes or modifications may be suggested to those skilled in the art in light of them, and it is understood that they are included within the present invention and the appended claims.

Claims

**Claim 1** A composition for delivering a pharmaceutical active ingredient (API), comprising a biopolymer and at least one API. **Claim 2** The composition according to claim 1, wherein the API and the biopolymer are stably dispersed to form the composition together. **Claim 3** The composition according to claim 1 or 2, wherein the composition comprises biopolymer molecules mechanically treated into a stable homogeneous aqueous suspension. **Claim 4** The composition according to any one of claims 1 to 3, wherein the composition comprises a homogeneous aqueous suspension of insoluble and / or semi-soluble biopolymer particles. **Claim 5** The composition according to claim 4, wherein the stable homogeneous aqueous suspension comprises insoluble and / or semi-soluble biopolymer particles stably dispersed in a polar solvent. **Claim 6** The composition according to any one of claims 1 to 5, wherein the biopolymer consists of a stable homogeneous aqueous suspension composed of insoluble and / or semi-soluble biopolymer particles. **Claim 7** The composition according to any one of claims 1 to 6, wherein the biopolymer is selected from the group consisting of chitin, chitosan, cellulose, hemicellulose, lignin, amylose, actin, fibrin, collagen, silk, fibroin, keratin, wool, alginic acid, and mixtures thereof. **Claim 8** The composition according to any one of claims 1 to 6, wherein the biopolymer is selected from the group consisting of gelatin, pectin, starch, amylopectin, agarose, alginic acid, alginate, hyaluronic acid, RNA, DNA, xanthan gum, guar gum, latex, polymannan, suberin, cutin, cutan, and mixtures thereof. **Claim 9** The composition according to any one of claims 1 to 8, wherein the composition is formulated as a paste, ointment, cream, lotion, gel, or milk. **Claim 10** The composition according to any one of claims 1 to 8, wherein the composition is in a dry form. **Claim 11** The composition according to claim 10, wherein the composition is formulated as a tablet, capsule, pellet, granule, transdermal patch, implant, scaffold, or suppository. **Claim 12** The composition according to any one of claims 1 to 11, wherein the API is a pharmaceutical product selected from the group consisting of analgesics, anesthetics, antidotes, antibacterial agents, antispasmodics, anti-dementia agents, antidepressants, antiemetics, antifungal agents, antigout agents, anti-inflammatory drugs, anti-headache agents, anti-myasthenic agents, anti-mycobacterial drugs, anti-cancer drugs, anti-obesity agents, anti-parasitic agents, anti-Parkinson agents, antipsychotics, antispasmodics, antiviral agents, anxiolytics, bipolar agents, blood glucose regulators, blood products, cardiovascular drugs, central nervous system drugs, contraceptives, dental and oral agents, topical agents, electrolytes, minerals, metals, vitamins, gastrointestinal agents, genitourinary agents, adrenal hormones, pituitary hormones, prostaglandin hormones, sex hormones, thyroid hormones, adrenal hormone suppressants, pituitary hormone suppressants, thyroid hormone suppressants, immunological agents, infertility agents, inflammatory bowel disease agents, metabolic bone disease agents, ophthalmic agents, otic agents, respiratory tract agents, sexual disorder agents, skeletal muscle relaxants, sleep disorder agents, and mixtures thereof.

13. The pharmaceutical product contains acetaminophen, acetylsalicylic acid, acyclovir (including Zovirax TM ), acrivastine, adalimumab, alendronic acid, allopurinol, alogliptin, amitriptyline for depression, amitriptyline for pain / headache, amlodipine, amoxicillin, anastrozole, apixaban, aspirin TM , atenolol, atorvastatin, azathioprine, azithromycin, baclofen, beclometasone inhaler, beclometasone nasal spray, beclometasone skin cream, bendroflumethiazide, benzoyl peroxide, benzydamine, betahistine, betamethasone for eyes / ears / nose, betamethasone for skin, bimatoprost, bisacodyl, bisoprolol, brinzolamide, budesonide inhaler, budesonide nasal spray, budesonide rectal foam and enema, bumetanide, buprenorphine for pain, buscopan (hyoscine butylbromide), candesartan, carbamazepine, carbimazole, carbocisteine, carboxymethylcellulose sodium, carvedilol, cephalexin, cetirizine, Champix TM (varenicline), chloramphenicol, chlorhexidine, chlorphenamine (Piriton TM ), cinarizine, ciprofloxacin, citalopram, clarithromycin, clobetasol, clobetasone, clonazepam, clopidogrel, clotrimazole, clotrimazole for thrush (Canesten TM ) Co-amoxiclav, co-beneldopa, co-careldopa, co-codamol for adults, co-codamol for children, co-codaprin (aspirin and codeine), co-dydramol, codeine, colchicine, cyanocobalamin, cyclizine, dabigatran, dapagliflozin, dexamethasone tablets and solutions, diazepam, diclofenac, digoxin, dihydrocodeine, diltiazem, diphenhydramine, dipyridamole, doxart, domperidone, donepezil, dosulepin, doxazosin, doxycycline, duloxetine, edoxaban, empagliflozin, enalapril, eplerenone, erythromycin, escitalopram, esomeprazole, ezetimibe, felodipine, fentanyl, ferrous fumarate, ferrous sulfate, fexofenadine, finasteride, flucloxacillin, fluconazole, fluoxetine (Prozac TM ) Fluticasone inhalers, fluticasone nasal sprays and drops, fluticasone skin creams, folic acid, furosemide, fusidic acid, fybogel (ispaghula husk), gabapentin, GavisconT (alginic acid), gliclazide, glimepiride, glyceryl trinitrate (gtn), heparinoids, hydrocortisone, hydrocortisone buccal tablets, hydrocortisone for haemorrhoids and itching, hydrocortisone for skin, hydrocortisone injections, hydrocortisone rectal foam, hydrocortisone tablets, hydroxocobalamin, hyoscine hydrobromide (kwells and joy-rides), ibuprofen and codeine, ibuprofen for adults (Nurofen TM ) Ibuprofen for children, indapamide, irbesartan, isosorbide mononitrate and isosorbide dinitrate, isotretinoin capsules (Roaccutane TM ) Isotretinoin gel (Isotrex TM ) Ketoconazole, Labetalol, Lactulose, Lamotrigine, Lansoprazole, Latanoprost, Lercanidipine, Letrozole, Levetiracetam, Levothyroxine, Lidocaine for Oral and Throat, Lidocaine for Hemorrhoids and Anal Itching, Lidocaine Skin Cream, Linagliptin, Lisinopril, Lithium, Loperamide, Loratadine (Clarityn TM ) Lorazepam, Losartan, Low-dose Aspirin, Lymecycline, Macrogol, Mebendazole, Mebeverine, Melatonin, Mesalazine, Metformin, Methadone, Methotrexate, Methylphenidate for Adults, Methylphenidate for Children, Metoclopramide, Metoprolol, Metronidazole, Mirabegron, Mirtazapine, Molnupiravir (Lagevrio TM ) Mometasone for Skin, Mometasone Inhaler, Mometasone Nasal Spray, Montelukast, Morphine, Naproxen, Nepafenac, Nicorandil, Nifedipine, Nitrofurantoin, Nortriptyline, Nystatin, Olanzapine, Olmesartan, Omeprazole, Oxybutynin, Oxycodone, Pantoprazole, Paracetamol for Adults, Paracetamol for Children (including Calpol), Paroxetine, Paxlovid, Peppermint Oil, Pepto-Bismol TM Perindopril, Phenoxymethylpenicillin, Phenytoin, Pioglitazone, Pravastatin, Prednisolone Tablets and Prednisolone Solution, Pregabalin, Prochlorperazine, Promethazine (Phenergan TM ) Propranolol, Pseudoephedrine (including Sudafed TM ), Rabeprazole, Ramipril, Ranitidine, Remdesivir (VekluryT), Risedronate, Risperidone, Rivaroxaban, Ropinirole, Rosuvastatin, Salbutamol Inhaler, Saxagliptin, Senna, Sertraline, Sildenafil (Viagra TM ), Simeticone, Simvastatin, Sitagliptin, Sodium Valproate, Solifenacin, Sotalol, Sotrovimab (Xevudy TM ) Sulfasalazine, Sumatriptan, Tadalafil, Tamsulosin, Temazepam, Terbinafine, Thiamine (Vitamin B1), Ticagrelor, Toltrazuril, Topiramate, Tramadol, Tranexamic acid, Trazodone, Trimethoprim, Valproic acid, Valsartan, Varenicline (Champix TM ) The composition according to claim 12, selected from the group consisting of Venlafaxine, Verapamil, Zolpidem, Zopiclone and mixtures thereof.

14. The composition according to any one of claims 1 to 11, wherein the API is a cosmetic selected from the group consisting of compounds for moisturizing the skin, compounds for improving the skin appearance, compounds for protecting against environmental damage, compounds for combating the effects of aging, compounds for removing wrinkles and / or sunspots, and / or compounds for preventing any of the following skin conditions: Acne, acne / folliculitis, acne scars, skin aging, blemishes, broken blood vessels, brown spots or other discolored skin, cellulite, creases around the mouth or nose, deflated or sunken cheeks, temples, lips and around the eyes, dull, discolored skin, thick facial or body hair, enlarged pores, tired or fatigued appearance, fine lines and creases, rough, cracked skin, flushed appearance, freckles on the forehead, furrows or wrinkles, hair loss, hair removal, hirsutism and hypertrichosis, hyperpigmentation, melasma, rosacea, sagging or volume loss, skin scarring, skin cancer, spider veins on the legs and face, sun-damaged skin, sunspots, tattoo removal, texture and color changes, tiny lines near the eyes or mouth, visible facial blood vessels, wrinkles and fine lines and mixtures thereof.

15. The composition according to any one of claims 1 to 11, wherein the API is a cosmetic compound selected from the group consisting of antioxidants (e.g., resveratrol, vitamin C), alpha-hydroxy acids (AHA), hyaluronic acid, retinoids (e.g., retinol), vitamins (e.g., vitamin A, vitamin E), resorcinol, benzoyl peroxide, salicylic acid, ceramides, niacinamide, sulfur, sodium fluoride, sodium monophosphate, clioquinol, haloprogin, miconazole nitrate, povidone-iodine, tolnaftate, undecylenic acid, calcium undecylenate, copper undecylenate, zinc undecylenate, clotrimazole bacitracin, chlortetracycline, neomycin sulfate, tetracycline hydrochloride, aluminum chloride, aluminum chlorohydrate, aluminum chlorohydrex polyethylene glycol, aluminum chlorohydrex propylene glycol, aluminum dichlorohydrate, aluminum dichlorohydrex polyethylene glycol, aluminum dichlorohydrex propylene glycol, aluminum sesquichlorohydrate, aluminum sesquichlorohydrex polyethylene glycol, aluminum sesquichlorohydrex propylene glycol, aluminum zirconium octachlorohydrate, aluminum zirconium octachlorohydrex gly, aluminum zirconium pentachlorohydrate, aluminum zirconium pentachlorohydrex gly, aluminum zirconium tetrachlorohydrate, aluminum zirconium tetrachlorohydrex gly, aluminum zirconium trichlorohydrate, aluminum zirconium trichlorohydrex gly, allantoin, aluminum hydroxide gel, calamine, cocoa butter, cod liver oil, dimethicone, glycerin, kaolin, lanolin, mineral oil, sodium bicarbonate, zinc acetate, zinc carbonate, zinc oxide, aluminum acetate, aluminum sulfate, witch hazel, selenium sulfide, zinc pyrithione, selenium sulfide, coal tar, hydroquinone, benzocaine, lidocaine and mixtures thereof.

16. A method of delivering a pharmaceutical active ingredient (API) to a subject in need thereof, comprising (i) To provide a delivery composition according to any one of claims 1 to 15; and (ii) Administering the composition to a subject, A method comprising.

17. The method according to claim 16, wherein the composition is administered by an administration route selected from the group consisting of topical administration, oral administration, sublingual administration, buccal administration, rectal administration, vaginal administration, intraocular administration, intratympanic administration, nasal administration, cutaneous administration and transdermal administration.

18. The method according to claim 16 or 17, wherein the composition is formulated as a paste, ointment, cream, lotion, gel or emulsion (milk).

19. The method according to claim 16 or 17, wherein the composition is in the form of a tablet, capsule, pellet, granule, film, transdermal patch, implant, scaffold or suppository.

20. A method for topically delivering a pharmaceutical active ingredient (API) to a subject in need thereof, comprising: (i) Providing a delivery composition comprising a biopolymer according to any one of claims 1 to 15 and at least one API; (ii) Applying the composition to the body of the subject, A method comprising.

21. The method according to claim 20, wherein the composition is applied to the surface of the body of the subject selected from the group consisting of hands, arms, legs, feet, torso, chest, face, neck and scalp.

22. The method according to claim 20, wherein the composition is applied as a paste, ointment, cream, lotion, gel or emulsion (milk).

23. The method according to claim 20, wherein the composition is applied as a transdermal patch.

24. A method for orally delivering a pharmaceutical active ingredient (API) to a subject in need thereof, comprising: (i) Providing a mixture comprising an API mixed in a biopolymer composition; and (ii) Drying the mixture to obtain a dried product; and (iii) Orally administering the dried product to the subject, A method comprising.

25. The method according to claim 24, wherein the composition is formulated as a tablet, capsule, pellet or granule.

26. A method for manufacturing a delivery composition according to any one of claims 1 to 15, comprising mechanically treating an API and a biopolymer(s) together under high shear conditions and / or under high mechanical energy to obtain a stable homogeneous aqueous composition.

27. The method according to claim 26, wherein the mechanical treatment is carried out until a stable homogeneous aqueous suspension is obtained, said suspension comprising insoluble and / or semi-soluble particles in which the API is dispersed.

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