WO2020113289A1 - Formulations comprising non-animal derived hydroxyproline and their use - Google Patents
Formulations comprising non-animal derived hydroxyproline and their use Download PDFInfo
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- WO2020113289A1 WO2020113289A1 PCT/AU2019/051349 AU2019051349W WO2020113289A1 WO 2020113289 A1 WO2020113289 A1 WO 2020113289A1 AU 2019051349 W AU2019051349 W AU 2019051349W WO 2020113289 A1 WO2020113289 A1 WO 2020113289A1
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- hydroxyproline
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Classifications
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Definitions
- THIS INVENTION relates to formulations having a non-animal-derived source of hydroxyproline.
- the formulations are useful for a variety of applications, such as treatment of hydroxyproline deficiency associated with, for example, vegan or vegetarian diets that are deficient in animal collagen and/or the promotion of collagen synthesis.
- hydroxyproline is an essential component of creating collagen and will directly stimulate collagen production, renewal and repair.
- Hydroxyproline is not an essential amino acid as it can be made in our body by hydroxylating proline with vitamin C. However, it may be conditionally essential when dietary supply fails to meet body requirements in times of increased physical demand, growth phases, aging and/or inadequate dietary supply of vitamin C and proline or insufficient endogenous production to meet demands. Further to the above, plant sources of hydroxyproline such as moss, are not commonly consumed in adequate levels to be a reliable or common source of plant-based hydroxyproline.
- the present invention is directed to formulations and methods for preventing or treating hydroxyproline deficiency and/or promoting collagen production. Also disclosed are methods for making said formulation, such as a dietary supplement or a topical formulation.
- the invention relates to formulations, such as orally administrable and topical formulations, comprising one or a plurality of non-animal- derived and/or plant-derived hydroxyproline sources and optionally one or more of a sweetening agent, a flavouring agent and a further amino acid for use in preventing and/or treating a hydroxyproline deficiency in a subject.
- the formulation is substantially free of animal-derived components, such as animal-derived amino acids.
- the invention provides a formulation comprising, consisting or consisting essentially of:
- the formulation is a substantially vegetarian and/or vegan formulation.
- the non-animal-derived hydroxyproline is or comprises L-hydroxyproline .
- the non- animal-derived hydroxyproline is, is derived from or comprises a bacteria-derived hydroxyproline source, an algae-derived hydroxyproline source and/or a plant-derived hydroxyproline source.
- the plant-derived hydroxyproline source is or comprises a corn-derived hydroxyproline source and/or a moss-derived hydroxyproline source.
- the further amino acid is selected from the group of glycine, proline, alanine, leucine, isoleucine, valine, lysine, glutamine, threonine, phenylalanine, methionine, tryptophan, histidine, taurine, and any combination thereof.
- the formulation comprises from about 1 wt% to about 99 wt% of the non- animal-derived hydroxyproline source. In one embodiment, the formulation comprises from about 1 wt% to about 95 wt% of the further amino acid.
- the formulation comprises from about 0.5 wt% to about 5 wt% of the sweetening agent.
- the formulation comprises from about 0.5 wt% to about 5 wt% of the colouring agent.
- the formulation comprises from about 1 wt% to about 10 wt% of the flavouring agent.
- the formulation of the present aspect further comprises a saponin source.
- the saponin source is preferably derived from Astragalus membranaceus and/or Panax notoginseng.
- the formulation comprises from about 0.1 wt% to about 2 wt% of the saponin source.
- the formulation is in the form of a supplement.
- the formulation is a protein supplement.
- the formulation is in the form of a food product.
- the formulation is in the form of a topical formulation.
- the formulation is for preventing or treating a hydroxyproline deficiency and/or promoting collagen production in a subject
- the invention resides in a supplement formulation comprising:
- a further amino acid such as glycine, proline, alanine and any combination thereof;
- the vitamin is selected from the group consisting of vitamin A, vitamin Bi, vitamin B2, vitamin B3, vitamin B ⁇ , vitamin B7, vitamin B12, vitamin C, vitamin D3, vitamin E and any combination thereof.
- the invention provides a method of producing the formulation of the first aspect, including the step of combining the non-animal- derived hydroxyproline source or non-animal-derived hydroxyproline and/or one or more components or derivatives thereof with the further amino acid, the vitamin, the one or more natural extracts, the sweetening agent, the colouring agent, the flavouring agent and/or the pharmaceutically acceptable carrier, diluent and/or excipient to thereby produce the formulation.
- the invention provides a formulation produced according to the method of the second aspect.
- the invention provides a formulation according to the first and third aspects, for use in:
- the invention provides a method of promoting collagen production in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation according to the first and third aspects, to thereby promote collagen production in the subject.
- the invention provides a method of treating and/or preventing a hydroxyproline deficiency in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation according to the first and third aspects, to thereby treat and/or prevent said hydroxyproline deficiency in the subject.
- the hydroxyproline deficiency is characterised by one or more of collagen deficiency, gastrointestinal dysfunction, arthritis, osteoarthritis, wrinkles, premature ageing, chronic fatigue syndrome, fibromyalgia, pain and recurrent injuries.
- the subject is suitably a human.
- indefinite articles“a” and“an” may refer to one entity or a plurality of entities and are not to be read or understood as being limited to a single entity.
- “a” subject includes one subject, one or more subjects or a plurality of subjects
- the present inventors have created an improved formulation, which is suitable for use by vegetarians and/or vegans, and when administered, for example, orally or topically to a subject is designed to compensate for a dietary hydroxyproline deficiency.
- the formulations described herein which include a non- animal-derived hydroxyproline source and optionally one or more of a pharmaceutically acceptable carrier, diluent and/or excipient, a further amino acid, a sweetening agent, a colouring agent and/or a flavouring agent, are designed to, for example, promote the production of collagen in a subject upon administration thereto.
- the formulation is in the form of a dietary supplement, a fortified food product and/or a topical product.
- the invention provides a formulation for preventing or treating a hydroxyproline deficiency in a subject comprising, consisting or consisting essentially of:
- non- animal-derived hydroxyproline such as from one or a plurality of non- animal-derived hydroxyproline sources
- a pharmaceutically acceptable carrier diluent and/or excipient, a further amino acid, a vitamin, a natural extract, a mineral, a sweetening agent, a colouring agent and/or a flavouring agent.
- hydroxyproline is an amino acid produced by hydroxylation of the amino acid, proline. Hydroxyproline differs from proline by the presence of a hydroxyl (OH) group attached to the C (gamma) atom. Other forms of hydroxyproline also exist in nature, notably 2,3-cis 3,4-trans-dihydroxyproline, as well as L- and D-isomers.
- hydroxyproline as used herein broadly refers to all the above mentioned forms, unless expressly stated otherwise.
- the non-animal-derived hydroxyproline source is or comprises L- hydroxyproline.
- the invention also relates to ionic forms and other derivatives of hydroxyproline that may be transformed to the pure form during digestion and/or intestinal absorption.
- the invention further relates to hydroxyproline derivatives, such as chelated hydroxyproline compounds (e.g., for slow release), hydroxyproline-rich glycoproteins (HRGPs; a major group of plant and/or algal wall glycoproteins), acylated derivatives, alkali metal salts, earth alkali metal salts, acid addition salts, esters, amides and ethers of hydroxyproline and the N-alkyl derivatives as well as oligo- and polypeptides thereof.
- the plant- derived hydroxyproline source is or comprises an algal-derived hydroxyproline source.
- the non- animal-derived hydroxyproline source of the present invention may be produced by any method known in the art.
- Nonlimiting examples include proteolytic extraction, chemical synthesis (see, e.g., JP2002088059A), microbial fermentation and enzymatic conversion (e.g., of proline).
- Methods of microbial fermentation to produce hydroxyproline are disclosed in CN105837488A and CN103509813A, which are incorporated by reference herein.
- Extraction and purification of components of plant extracellular matrix extract is well known in the art.
- the extraction and purification of hydroxyproline-rich protein is described by Hood et ah, 1988, Plant Physiol. 87:138-142, which is incorporated by reference herein.
- the relative proportion of plant-derived hydroxyprolines can vary depending upon the source of the extract, i.e., the type of plant used and on the extraction technique employed. For example, an extract of Kudzu leaves contains more hydroxyproline-rich glycoproteins than an extract from maize.
- the non-animal-derived hydroxyproline source may be obtainable or derivable, at least in part, from any non-animal source, such as microbe-derived (e.g., bacterial-derived, fungal-derived and algal-derived) and/or plant-derived hydroxyproline.
- the term also includes synthetically manufactured hydroxyproline, although hydroxyproline derived from natural sources is preferred.
- the plant-derived or plant-based hydroxyproline source may be obtainable or derivable from any plant or plant part.
- Plant-based sources include trees, vines, plant seeds, bark, roots, leaves, bulbs, tubers, nuts and/or fruit, although without limitation thereto.
- Plants may include grasses, such as bamboo, cereals, legumes (e.g ., Alfalfa - Medicago sativa ), seaweed, leafy vegetables, cruciform vegetables, mosses (e.g., Chondrus crispus) and fungi, although without limitation thereto.
- the non-animal-derived hydroxyproline sources are or comprise a plant-derived hydroxyproline source, such as a com or maize-derived hydroxyproline source or a moss-derived hydroxyproline source.
- the non-animal-derived hydroxyproline source is isolated or substantially purified.
- isolated or purified is meant material that has been removed from its natural state or otherwise been subjected to human manipulation.
- Isolated or purified material may be substantially or essentially free from components that normally accompany it in its natural state, or may be manipulated so as to be in an artificial state together with components that normally accompany it in its natural state.
- Isolated material may be in native, chemical synthetic or recombinant form.
- the formulation suitably includes the one or plurality of non- animal-derived hydroxyproline sources in a wt% concentration of about 0.1% to about 99% or any range therein such as, but not limited to, about 1% to about 75% or about 2% to about 30%.
- the one or plurality of non-animal-derived hydroxyproline sources are present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 5.75, 6, 6.25, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 8.25, 8.5, 8.75, 9, 9.25, 9.5, 9.75, 10, 10.25, 10.5, 10.75, 11, 11.25, 11.5, 11.75, 12, 12.25, 12.5, 12.75, 13, 13.25, 13.5, 13.75, 14, 14.25, 14.5, 14.75, 15, 15.25, 15.5, 15.75, 16, 16.25, 16.5, 16.75, 17, 17.25, 17.5, 17.75, 18, 18.25, 18.5, 18.75, 19, 19.25, 19.5, 19.75, 20, 21,
- the formulation comprises from about 1 wt% to about 95 wt% of the one or plurality of non-animal-derived hydroxyproline sources.
- the formulation suitably includes non- animal-derived hydroxyproline in a wt% concentration of about 0.1% to about 99% or any range therein such as, but not limited to, about 1% to about 75% or about 2% to about 30%.
- non- animal-derived hydroxyproline is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2,
- the formulation comprises from about 1 wt% to about 95 wt% of non- animal-derived hydroxyproline.
- the formulation of the present aspect is a substantially vegetarian and/or vegan formulation.
- the term“ vegetarian” refers to a product or formulation, including but not limited to foods and supplements, which are not made from or with the aid of products derived from animals that have died, have been slaughtered, or animals that die as a result of being eaten. Such animals may include farmed, wild or domestic animals, including, but not limited to, livestock poultry, game, fish, shellfish, Crustacea, amphibians, tunicates, echinoderms, molluscs and insects.
- a product can be vegetarian if it includes dairy products and eggs.
- the term“vegan” refers to a product including, but not limited to foods and supplements, which are not made from or with the aid of animals or animal products (including products from living animals).
- the formulation of the present aspect is in the form of a supplement, such as a protein supplement.
- a supplement refers to a supplement intended to supplement a diet of food and water, where the diet is sufficient to support life.
- a supplement may contain vitamins, minerals, herbs or other botanicals, amino acids, enzymes, organ tissues, glandular metabolites, or combinations thereof.
- Supplements may be administered by any convenient means, including parenteral or enteral routes. Enteral routes may include oral, gastric, or subgastric administration, including rectal administration. In a preferred form, the supplements of the present invention are administered orally.
- the formulation may be in the form of a capsule, a cachet, a pill, a tablet, a powder, a granule, a pellet, a bead, a particle, a troche, a lozenge, and/or a gel.
- the formulation is in the form of a food product.
- suitable food products include a bar, such as a cereal or protein bar, a breakfast cereal, such as granola, a cracker, a biscuit and a snack, such as a snack chip.
- a bar such as a cereal or protein bar
- a breakfast cereal such as granola
- a cracker such as granola
- a biscuit such as a snack chip.
- the formulation is a topical formulation.
- a topical formulation of the invention may comprise a pharmaceutically acceptable carrier, diluent or excipient, including, but without limitation thereto, an effective amount of a moisturising, solubilising and/or substantive ingredient.
- a pharmaceutically acceptable carrier, diluent or excipient including, but without limitation thereto, an effective amount of a moisturising, solubilising and/or substantive ingredient.
- a useful reference describing pharmaceutically acceptable carriers, diluents and excipients is Remington’s Pharmaceutical Sciences (Mack Publishing Co. NJ USA, 1991).
- the formulation has a semi-solid consistency of a mousse, gel, cream, lotion, oil, spray or paint for ease of storage and application.
- the formulation preferably has the consistency of a cream.
- an effective amount of a thickener may be incorporated within the formulation to obtain the desired viscosity and consistency of the product for example, as use as a cream, lotion or ointment.
- the formulation may be delivered using the following non-limiting examples: carbomer gel, serum, spray, bath oils, massage oils, patches, nanopatches, nanodelivery systems, compresses, poultices, tape, bandages, strapping tape, dose delivery devices, slow release devices, epidermal injection, subcutaneous injection, dropper, clothing, dressings, gauze and/or injection.
- the further amino acid of the present aspect can be any known in the art, inclusive of essential and non-essential amino acids, as well as derivatives or variants thereof, such as amino acid salts.
- Nonlimiting examples include leucine, isoleucine, valine, lysine, glutamine, threonine, phenylalanine, methionine, tryptophan, histidine, taurine, arginine, serine, proline, glycine, alanine, ornithine, citrulline, urocanic acid, asparagine and tyrosine.
- the further amino acid is selected from the group of leucine, isoleucine, valine, lysine, glutamine, threonine, phenylalanine, methionine, tryptophan, histidine, taurine, and any combination thereof.
- the formulation may include one or more further amino acids in addition to hydroxyproline, such as those hereinbefore described, in a wt% concentration of about 0.1% to about 99% or any range therein such as, but not limited to, about 1% to about 35% or about 2% to about 20%.
- the further amino acid is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3,
- the formulation comprises from about 1 wt% to about 95 wt% of the further amino acid.
- sweetening agent refers to natural or artificial compounds used to increase the sweetness of the present formulation.
- sweetening agents include carbohydrate sweetening agents, (i.e., sugars and other carbohydrate sweetening agents) and non-carbohydrate sweetening agents.
- sucrose refers to sucrose and the constituents of sucrose (e.g., glucose and/or fructose, sugar syrup, malt syrup, maple syrup, starch syrup, glucose syrup, high-fructose syrups such as high-fructose corn syrup, honey, molasses) and other carbohydrates that can be used as sweetening agents or a source of these.
- other carbohydrate sweetening agents refers to, for example, sugar alcohols, such as xylitol, maltitol, lactitol and sorbitol.
- suitable examples of the non-carbohydrate sweetening agents include e.g. stevia, aspartame (phenylalanine), acesulfame potassium (Ace-K), saccharin, cyclamates and sucralose.
- the sweetener may include a low calorie sweetener, a natural sweetener, a non-nutritive sweetener and/or an artificial sweetener. Additionally, the sweetener may be naturally or synthetically derived.
- the sweetening agent or combination of sweetening agents are present at a concentration of about 0.01 to about 20 wt%, more preferably about 0.05 to about 10 wt% or even more preferably about 0.1 to about 2 wt%.
- the formulation of the invention can include one or more sweetening agents, such as those hereinbefore described, in a wt% concentration of about 0.1% to about 10% or any range therein such as, but not limited to, about 1% to about 5% or about 0.2% to about 2%.
- the sweetening agent is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 5.75, 6, 6.25, 6.5,
- the formulation comprises from about 0.5 wt% to about 5 wt% of the sweetening agent.
- the colouring agent may be any as are known in the art.
- a wide range of food grade colouring agents is used by the food industry in order to enhance the optical appearance of food, dietary supplements and the like.
- known food grade colouring agents only a few are natural, such as betanoin or chlorophyll, for instance.
- Most food grade colouring agents are either synthetic analogues of naturally occurring substances - so-called nature identical substances - or are fully artificial.
- the formulation of the invention can include one or more colouring agents, such as those hereinbefore described, in a wt% concentration of about 0.1% to about 20% or any range therein such as, but not limited to, about 1% to about 15% or about 2% to about 12%.
- the colouring agent is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1,
- the formulation comprises from about 0.5 wt% to about 5 wt% of the colouring agent.
- the flavouring agents of the invention may be any natural or non-natural substance which adds or enhances flavour.
- the flavouring agents may also comprise natural or non-natural stabilizers, anti-caking and/or flow agents.
- Flavouring agents are typically comprised of a flavoured substance(s) and complexes manufactured or extracted from nature in liquid or powdered form to impart a particular flavour into a product.
- Excipients are added to preserve, stabilize and maintain form and colour.
- Typical excipients may include flow agents, anticaking agents, antioxidants, including but not exclusively, maltodextrin, gum acacia, tapioca starch, propylene glycol and triacetin.
- the formulation may include one or more flavouring agents, such as those hereinbefore described, in a wt% concentration of about 0.1% to about 20% or any range therein such as, but not limited to, about 1% to about 15% or about 2% to about 10%.
- the flavouring agent is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1,
- the formulation comprises from about 1 wt% to about 10 wt% of the flavouring agent.
- the formulation of the present aspect further includes a filler, such as those known in the art.
- a filler is an ingredient added to provide bulk or some other non-nutritive purpose to a composition or formulation.
- the formulation further comprises a saponin source including one or more saponins, such as that derived from Astragalus membranaceus and/or Panax notoginseng.
- a preferred saponin source is AstraGin® which contains purified saponins isolated from the Astragalus membranaceus and Panax notoginseng plants.
- glycosidic triterpenoid compounds which produce foam in aqueous solution, have haemolytic activity in most cases, and possess immune adjuvant activity. It will also be appreciated that the term encompasses the saponin per se, as well as natural and pharmaceutically acceptable salts and pharmaceutically acceptable derivatives thereof. The term “saponin” also encompasses biologically active fragments thereof.
- the term“ saponin source” generally refers to any saponin source that is, or can be, obtained or derived from plants or plant parts, including synthetically manufactured saponins. Natural saponins, however, are preferred.
- the saponin source is or comprises a saponin- rich extract or concentrate. It will be appreciated that such saponin-rich extracts or concentrates may be in any form, including liquid and solid forms.
- the formulation comprises from about 0.1 wt% to about 5 wt% (e.g., about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, and any range therein) of the saponin source. More particularly, the formulation comprises from about 0.1 wt% to about 2 wt% of the saponin source.
- the formulation of the present aspect further comprises one or more vitamins and/or minerals, such as electrolytes.
- vitamins include vitamin A (e.g., vitamin Ai retinol, axerophthol, a-carotene, b-carotene, g-carotene), B vitamins (e.g., Bi vitamins including: thiamin, aneurin, thiamine, pyrophosphate, cocarboxylase; B2 vitamins including riboflavin, vitamin G, lactoflavin, hepatoflavin, ovoflavin, verdoflavin, riboflavin mononucleotide, FMN, riboflavin dinucleotide, FAD; Vitamin B 3 (niacin), Vitamin Be (pyridoxine, pyridoxal-5-phosphate), Vitamin B 7 (biotin), Vitamin B 12 (cobalamin, methylcobalamin)), Vitamin C (ascorbic acid, antiscorbutic vitamin, dehydro
- concentration may refer to percent weight/volume (w/v), percent weight/weight (w/w) or percent volume/volume (v/v) of a particular ingredient within the formulation as applicable.
- the formulation further comprises a pH modifier.
- the pH modifier may be any agent, substance or molecule that facilitates obtaining and/or maintaining an optimal pH for the formulation.
- the pH modifier may be a buffering agent, acid or base that facilitates achieving an acidic pH, an alkaline pH or neutral pH (i.e., about pH 7).
- the pH modifier is an acid, such as an organic acid.
- Organic acids may be any food acid, such as a carboxylic acid, that is suitable for human consumption and includes salts of said organic acids.
- Non-limiting examples include tartaric acid, citric acid, lactic acid, benzoic acid, acetic acid, malic acid, ascorbic acid, succinic acid, fumaric acid, oxalic acid and their salts (e.g tartrates, citrates, lactates etc).
- Preferred organic acids are citric acid, malic acid and ascorbic acid.
- the pH modifiers are present at a concentration of about 1-10% (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 wt% or any range therein) by weight in total, or preferably about 2-7% by weight in total.
- malic acid and/or citric acid is present at about up to 7.0% by weight of the formulation.
- the formulation of the present aspect may include one or more natural ingredients or extracts (inclusive of plant extracts and algal extracts), such as those that can serve as effective ingredients for reducing undesirable traits associated with aging and/or compounds for facilitating wound care in different skin care applications.
- Non limiting examples of such natural ingredients include fucoidan or extracts thereof, Moringa oleifera or extracts thereof, Aloe or extracts thereof, soy or extracts thereof, Cyathea medularis or extracts thereof, Centipeda cunninghamii or extracts thereof, Phyllanthus emblica or extracts thereof, Aphanizomenon flos-aquae or extracts thereof, Chlorella vulgaris or extracts thereof, Broccoli ( Brassica oleracea var.
- Chia e.g., Salvia hispanica, Salvia columbariae
- Chia e.g., Salvia hispanica, Salvia columbariae
- Citrus aurantium or extracts thereof Lonicera japonica or extracts thereof
- Olea europaea or extracts thereof Polypodium leucotomos or extracts thereof
- Camellia sinensis or extracts thereof Aristotelia chilensis or extracts thereof, berries or extracts thereof
- Theobroma cacao or extracts thereof Cocos nucifera or extracts thereof (inclusive of coconut water powder), Vitellaria nilotica or extracts thereof, Rosa rubiginosa or extracts thereof, Ceteryl olivate or extracts thereof, Theobroma cacao or extracts thereof, Glycine max or extracts thereof, Citrus sinensis or extracts thereof,
- the formulation is a supplement formulation comprising:
- a further amino acid such as glycine, proline, alanine and any combination thereof;
- a vitamin such as vitamin A, vitamin Bi, vitamin B 2 , vitamin B 3 , vitamin Be, vitamin B 7 , vitamin B 12 , vitamin C, vitamin D 3 , vitamin E and any combination thereof;
- the invention provides a method of producing the formulation according to the aforementioned aspect, including the step of combining the non-animal-derived hydroxyproline and/or one or more components or derivatives thereof with the further amino acid, the vitamin, the mineral, the natural extract, the sweetening agent, the colouring agent, the flavouring agent and/or the pharmaceutically acceptable carrier, diluent and/or excipient to thereby produce the formulation.
- the method of the present aspect suitably preserves the ability of the hydroxyproline to, for example, promote collagen synthesis and/or treat a hydroxyproline deficiency or a disease, disorder or condition associated therewith.
- preserving these properties may be achieved by avoiding exposing the formulation to excessive heat.
- combining the ingredients of the formulation at room temperature may improve the efficacy thereof.
- the invention provides a formulation produced according to the aforementioned aspect.
- the invention provides a formulation described herein, for use in: (i) promoting collagen production; and/or
- the hydroxyproline deficiency is characterised by one or more of collagen deficiency, gastrointestinal dysfunction, arthritis, osteoarthritis, wrinkles, premature ageing, chronic fatigue syndrome, fibromyalgia, pain, recurrent injuries.
- the invention provides a method of promoting collagen production in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation described herein, to thereby promote collagen production in the subject.
- administering is meant the introduction of a formulation (e.g., a formulation comprising, consisting or consisting essentially of a non- animal-derived hydroxyproline source, and one or more of a further amino acid, a sweetening agent, a colouring agent, a flavouring agent, a vitamin, a mineral, a natural extract and/or a pharmaceutically acceptable carrier, diluent and/or excipient) into a subject by a chosen route, and in particular by the oral and/or topical route.
- a formulation e.g., a formulation comprising, consisting or consisting essentially of a non- animal-derived hydroxyproline source, and one or more of a further amino acid, a sweetening agent, a colouring agent, a flavouring agent, a vitamin, a mineral, a natural extract and/or a pharmaceutically acceptable carrier, diluent and/or excipient
- terapéuticaally effective amount describes a quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent. For example, this can be the amount of the formulation hereinbefore described to: (a) promote collagen production; and/or (b) reduce, alleviate and/or prevent a disease, disorder or condition associated with the hydroxyproline deficiency.
- a“therapeutically effective amount” is sufficient to reduce or eliminate a symptom of such a disease, disorder or condition.
- a“therapeutically effective amount” is an amount sufficient to achieve a desired biological effect, for example an amount that is effective to promote collagen production in a subject with the hydroxyproline deficiency.
- a therapeutically effective amount of an agent is an amount sufficient to induce the desired result without causing a substantial cytotoxic effect in the subject.
- the effective amount of the formulation useful for, for example, reducing, alleviating and/or preventing a disease, disorder or condition associated with a hydroxyproline deficiency will be dependent on the subject being treated, the type and severity of any associated disease, disorder and/or condition, and the manner of administration of the therapeutic composition.
- a given dosage of the formulation is applied as a single application or a plurality of applications over a given time period (e.g ., for as long as the subject requires treatment), where the dosing schedule is administered over a given time period, examples of which include hourly, daily, weekly, biweekly or monthly dosing schedules.
- one or more additional agents as are known in the art for reducing, alleviating and/or preventing a disease, disorder and/or condition associated with hydroxyproline deficiency, or one or more symptoms associated therewith, may be administered to a subject in need thereof in addition to a therapeutically effective amount of the formulation described herein. That is, one or more additional agents traditionally used for the treatment and/or prevention of a disease, disorder and/or condition associated with hydroxyproline deficiency, such as an anti-inflammatory agent, may be administered to a subject in addition to a therapeutically effective amount of the formulation.
- any safe route of administration may be employed for providing a subject with a formulation of the present aspect.
- oral, rectal, parenteral, sublingual, buccal, intravenous, intra-articular, intra-muscular, intra-dermal, subcutaneous, inhalational, intraocular, intraperitoneal, intracerebroventricular, transdermal, and the like may be employed.
- the formulation is orally and/or topically (i.e., transdermally) administered.
- Dosage forms include powder, tablets, dispersions, suspensions, injections, solutions, syrups, troches, capsules, suppositories, aerosols, transdermal patches, liquid drops, diluted in beverage, gum, confectionary, oral strips, gel, jelly, and the like. These dosage forms may also include injecting or implanting controlled releasing devices designed specifically for this purpose or other forms of implants modified to act additionally in this fashion.
- the above formulations may be administered in a manner compatible with the dosage formulation, and in such amount as is pharmaceutically/therapeutically- effective.
- the dose administered to a subject should be sufficient to effect a beneficial response (e.g., a reduction or amelioration in symptoms of a disease, disorder or condition associated with hydroxyproline deficiency) in a subject over an appropriate period of time.
- the quantity of the formulation to be administered may depend on the subject to be treated, inclusive of the age, sex, weight and general health condition thereof, factors that will depend on the judgement of a practitioner of ordinary skill in the art.
- the invention provides a method of treating and/or preventing a hydroxyproline deficiency in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation described herein, to thereby treat and/or prevent said hydroxyproline deficiency in the subject.
- treating “treat” or“ treatment” refers to a therapeutic intervention, course of action or protocol that at least ameliorates a symptom of a disease, disorder or condition associated with the hydroxyproline deficiency after said disease, disorder or condition and/or its symptoms have at least started to develop.
- preventing refers to therapeutic intervention, course of action or protocol initiated prior to the onset of a disease, disorder or condition associated with the hydroxyproline deficiency and/or a symptom thereof so as to prevent, inhibit or delay or development or progression of said disease, disorder or condition or the symptom.
- a“ prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of a disease, disorder or condition associated with hydroxyproline deficiency or exhibits only early signs for the purpose of decreasing the risk of developing such a disease, disorder or condition.
- the hydroxyproline deficiency may be characterised by one or more diseases, disorders or conditions as are known in the art.
- the hydroxyproline deficiency is characterised by one or more of collagen deficiency, gastrointestinal dysfunction, arthritis, osteoarthritis, wrinkles, premature ageing, chronic fatigue syndrome, fibromyalgia, pain, and recurrent injuries.
- hydroxyproline is a major component of the protein collagen. Hydroxyproline and proline play key roles for collagen stability. Defects in collagen synthesis lead to easy bruising, internal bleeding, breakdown of connective tissue of the ligaments and tendons, and increased risk to blood vessel damage.
- Increased spill of hydroxyproline in the urine is generally associated with breakdown of connective tissue due to a disease process and may also be a manifestation of vitamin C deficiency. Deficiency of hydroxyproline is only known to occur if there is a deficiency of vitamin C.
- subject includes both human and veterinary subjects.
- administration to a subject can include administration to a human subject or a veterinary subject.
- the subject is a human.
- therapeutic uses according to the invention may also be applicable to mammals such as domestic and companion animals, performance animals such as horses, livestock, and laboratory animals.
- Example 1 provides an embodiment of the formulation as a dietary protein supplement.
- Example 2 provides a further embodiment of the formulation as a dietary protein supplement.
- Example 3 provides an embodiment of the formulation of the invention as an oral capsule designed as a cosmetic or beauty product to promote collagen production.
- the two powdered ingredients each at 250 mg are mixed together to make 500mg, which is subsequently encapsulated into a vegan capsule with optionally a suitable amount of a natural excipient, flow agent or filler.
- Amla Plantanthus emblica
- ascorbate or seabuckthorn fruit extract
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Abstract
Provided herein is a formulation that contains non-animal-derived hydroxyproline, and one or more of a further amino acid, a sweetening agent, a colouring agent, a flavouring agent, a vitamin, a mineral, a natural extract and/or a pharmaceutically acceptable carrier, diluent and/or excipient as well as methods of making same. Methods of promoting collagen production and treating a hydroxyproline deficiency in a subject using said formulation is further described herein.
Description
TITLE
FORMULATIONS COMPRISING NON-ANIMAL DERIVED HYDROXYPROLINE AND THEIR USE
TECHNICAL FIELD
THIS INVENTION relates to formulations having a non-animal-derived source of hydroxyproline. The formulations are useful for a variety of applications, such as treatment of hydroxyproline deficiency associated with, for example, vegan or vegetarian diets that are deficient in animal collagen and/or the promotion of collagen synthesis.
BACKGROUND
Over time our food and dietary habits have changed. Cultural habits, traditions and food choices are becoming less diverse. By way of example, the modern western diet is becoming increasingly deficient in collagen. Organ meats, offal, gristle, tendons, tongue, brawn, stocks from carcass, skins and rind etc., which are a source of collagen, are not a regular part of most diets.
Additional vegan and vegetarian subjects avoid animal products and therefore generally have little or no animal-derived collagen in their diet. However; historically human and animal herbivores have consumed insects within their plant matter that supplied animal proteins and collagen.
Animal collagen supplies a particular amino acid, that is hydroxyproline. Hydroxyproline is an essential component of creating collagen and will directly stimulate collagen production, renewal and repair. Hydroxyproline is not an essential amino acid as it can be made in our body by hydroxylating proline with vitamin C. However, it may be conditionally essential when dietary supply fails to meet body requirements in times of increased physical demand, growth phases, aging and/or inadequate dietary supply of vitamin C and proline or insufficient endogenous production to meet demands. Further to the above, plant sources of hydroxyproline such as moss, are not commonly consumed in adequate levels to be a reliable or common source of plant-based hydroxyproline.
Accordingly, there exists a need for improved formulations or supplements having one or more non- animal-derived sources of hydroxyproline suitable for preventing or treating hydroxyproline deficiency and in doing so may further promote collagen production in a subject.
SUMMARY
The present invention is directed to formulations and methods for preventing or treating hydroxyproline deficiency and/or promoting collagen production. Also disclosed are methods for making said formulation, such as a dietary supplement or a topical formulation.
In a broad form, the invention relates to formulations, such as orally administrable and topical formulations, comprising one or a plurality of non-animal- derived and/or plant-derived hydroxyproline sources and optionally one or more of a sweetening agent, a flavouring agent and a further amino acid for use in preventing and/or treating a hydroxyproline deficiency in a subject. Suitably, the formulation is substantially free of animal-derived components, such as animal-derived amino acids.
In a first aspect the invention provides a formulation comprising, consisting or consisting essentially of:
(i) non- animal-derived hydroxyproline and/or one or more components or derivatives thereof; and
(ii) one or more of a further amino acid, a sweetening agent, a colouring agent, a flavouring agent, a vitamin, a mineral, a natural extract and/or a pharmaceutically acceptable carrier, diluent and/or excipient.
In one embodiment, the formulation is a substantially vegetarian and/or vegan formulation.
In some embodiments, the non-animal-derived hydroxyproline is or comprises L-hydroxyproline .
Suitably, the non- animal-derived hydroxyproline is, is derived from or comprises a bacteria-derived hydroxyproline source, an algae-derived hydroxyproline source and/or a plant-derived hydroxyproline source. Preferably, the plant-derived hydroxyproline source is or comprises a corn-derived hydroxyproline source and/or a moss-derived hydroxyproline source.
In certain embodiments, the further amino acid is selected from the group of glycine, proline, alanine, leucine, isoleucine, valine, lysine, glutamine, threonine, phenylalanine, methionine, tryptophan, histidine, taurine, and any combination thereof.
In particular embodiments, the formulation comprises from about 1 wt% to about 99 wt% of the non- animal-derived hydroxyproline source.
In one embodiment, the formulation comprises from about 1 wt% to about 95 wt% of the further amino acid.
In particular embodiments, the formulation comprises from about 0.5 wt% to about 5 wt% of the sweetening agent.
In some embodiments, wherein the formulation comprises from about 0.5 wt% to about 5 wt% of the colouring agent.
In one embodiment, the formulation comprises from about 1 wt% to about 10 wt% of the flavouring agent.
Suitably, the formulation of the present aspect further comprises a saponin source. In this regard, the saponin source is preferably derived from Astragalus membranaceus and/or Panax notoginseng.
In one embodiment, the formulation comprises from about 0.1 wt% to about 2 wt% of the saponin source.
Suitably, the formulation is in the form of a supplement. Preferably, the formulation is a protein supplement.
In some embodiments, the formulation is in the form of a food product.
In alternative embodiments, the formulation is in the form of a topical formulation.
Suitably, the formulation is for preventing or treating a hydroxyproline deficiency and/or promoting collagen production in a subject
In one embodiment, the invention resides in a supplement formulation comprising:
(i) non- animal-derived hydroxyproline;
(ii) a further amino acid, such as glycine, proline, alanine and any combination thereof;
(iii) a vitamin and/or a mineral; and
(i) optionally one or more natural extracts.
In particular embodiments, the vitamin is selected from the group consisting of vitamin A, vitamin Bi, vitamin B2, vitamin B3, vitamin Bό, vitamin B7, vitamin B12, vitamin C, vitamin D3, vitamin E and any combination thereof.
In a second aspect, the invention provides a method of producing the formulation of the first aspect, including the step of combining the non-animal- derived hydroxyproline source or non-animal-derived hydroxyproline and/or one or
more components or derivatives thereof with the further amino acid, the vitamin, the one or more natural extracts, the sweetening agent, the colouring agent, the flavouring agent and/or the pharmaceutically acceptable carrier, diluent and/or excipient to thereby produce the formulation.
In a third aspect, the invention provides a formulation produced according to the method of the second aspect.
In a fourth aspect, the invention provides a formulation according to the first and third aspects, for use in:
(i) promoting collagen production; and/or
(ii) the therapeutic and/or prophylactic treatment of a hydroxyproline deficiency;
in a subject.
In a fifth aspect, the invention provides a method of promoting collagen production in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation according to the first and third aspects, to thereby promote collagen production in the subject.
In a sixth aspect, the invention provides a method of treating and/or preventing a hydroxyproline deficiency in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation according to the first and third aspects, to thereby treat and/or prevent said hydroxyproline deficiency in the subject.
Suitably, the hydroxyproline deficiency is characterised by one or more of collagen deficiency, gastrointestinal dysfunction, arthritis, osteoarthritis, wrinkles, premature ageing, chronic fatigue syndrome, fibromyalgia, pain and recurrent injuries.
With respect to the invention of the fourth, fifth and sixth aspects, the subject is suitably a human.
Throughout this specification, unless otherwise indicated, “ comprise “ comprises” and“ comprising” are used inclusively rather than exclusively, so that a stated integer or group of integers may include one or more other non-stated integers or groups of integers. Conversely, the terms“consist”,“ consists” and“ consisting” are used exclusively, such that a stated integer or group of integers are required or mandatory, and no other integers may be present.
The phrase“ consisting essentially of’ indicates that a stated integer or group
of integers are required or mandatory, but that other elements that do not interfere with or contribute to the activity or action of the stated integer or group of integers are optional.
As used in this specification the indefinite articles“a” and“an” may refer to one entity or a plurality of entities and are not to be read or understood as being limited to a single entity. For example,“a” subject includes one subject, one or more subjects or a plurality of subjects
DETAILED DESCRIPTION
The present inventors have created an improved formulation, which is suitable for use by vegetarians and/or vegans, and when administered, for example, orally or topically to a subject is designed to compensate for a dietary hydroxyproline deficiency. In this regard, the formulations described herein, which include a non- animal-derived hydroxyproline source and optionally one or more of a pharmaceutically acceptable carrier, diluent and/or excipient, a further amino acid, a sweetening agent, a colouring agent and/or a flavouring agent, are designed to, for example, promote the production of collagen in a subject upon administration thereto. Suitably, the formulation is in the form of a dietary supplement, a fortified food product and/or a topical product.
In one aspect, the invention provides a formulation for preventing or treating a hydroxyproline deficiency in a subject comprising, consisting or consisting essentially of:
(i) non- animal-derived hydroxyproline, such as from one or a plurality of non- animal-derived hydroxyproline sources; and
(ii) optionally one or more of a pharmaceutically acceptable carrier, diluent and/or excipient, a further amino acid, a vitamin, a natural extract, a mineral, a sweetening agent, a colouring agent and/or a flavouring agent.
It will be appreciated that hydroxyproline (Hyp) is an amino acid produced by hydroxylation of the amino acid, proline. Hydroxyproline differs from proline by the presence of a hydroxyl (OH) group attached to the C (gamma) atom. Other forms of hydroxyproline also exist in nature, notably 2,3-cis 3,4-trans-dihydroxyproline, as well as L- and D-isomers. The term hydroxyproline as used herein broadly refers to
all the above mentioned forms, unless expressly stated otherwise. In one particular embodiment, the non-animal-derived hydroxyproline source is or comprises L- hydroxyproline.
The invention also relates to ionic forms and other derivatives of hydroxyproline that may be transformed to the pure form during digestion and/or intestinal absorption. The invention further relates to hydroxyproline derivatives, such as chelated hydroxyproline compounds (e.g., for slow release), hydroxyproline-rich glycoproteins (HRGPs; a major group of plant and/or algal wall glycoproteins), acylated derivatives, alkali metal salts, earth alkali metal salts, acid addition salts, esters, amides and ethers of hydroxyproline and the N-alkyl derivatives as well as oligo- and polypeptides thereof. Accordingly, in certain embodiments, the plant- derived hydroxyproline source is or comprises an algal-derived hydroxyproline source.
The non- animal-derived hydroxyproline source of the present invention may be produced by any method known in the art. Nonlimiting examples include proteolytic extraction, chemical synthesis (see, e.g., JP2002088059A), microbial fermentation and enzymatic conversion (e.g., of proline). Methods of microbial fermentation to produce hydroxyproline are disclosed in CN105837488A and CN103509813A, which are incorporated by reference herein.
Extraction and purification of components of plant extracellular matrix extract, such as HRGPs, is well known in the art. By way of example, the extraction and purification of hydroxyproline-rich protein is described by Hood et ah, 1988, Plant Physiol. 87:138-142, which is incorporated by reference herein. The relative proportion of plant-derived hydroxyprolines can vary depending upon the source of the extract, i.e., the type of plant used and on the extraction technique employed. For example, an extract of Kudzu leaves contains more hydroxyproline-rich glycoproteins than an extract from maize.
Broadly, the non-animal-derived hydroxyproline source may be obtainable or derivable, at least in part, from any non-animal source, such as microbe-derived (e.g., bacterial-derived, fungal-derived and algal-derived) and/or plant-derived hydroxyproline. The term also includes synthetically manufactured hydroxyproline, although hydroxyproline derived from natural sources is preferred.
By way of example, the plant-derived or plant-based hydroxyproline source may be obtainable or derivable from any plant or plant part. Plant-based sources include trees, vines, plant seeds, bark, roots, leaves, bulbs, tubers, nuts and/or fruit, although without limitation thereto. Plants may include grasses, such as bamboo, cereals, legumes ( e.g ., Alfalfa - Medicago sativa ), seaweed, leafy vegetables, cruciform vegetables, mosses (e.g., Chondrus crispus) and fungi, although without limitation thereto. In one embodiment, the non-animal-derived hydroxyproline sources are or comprise a plant-derived hydroxyproline source, such as a com or maize-derived hydroxyproline source or a moss-derived hydroxyproline source.
In particular embodiments, the non-animal-derived hydroxyproline source is isolated or substantially purified. For the purposes of this invention, by“ isolated” or “ purified' is meant material that has been removed from its natural state or otherwise been subjected to human manipulation. Isolated or purified material may be substantially or essentially free from components that normally accompany it in its natural state, or may be manipulated so as to be in an artificial state together with components that normally accompany it in its natural state. Isolated material may be in native, chemical synthetic or recombinant form.
The formulation suitably includes the one or plurality of non- animal-derived hydroxyproline sources in a wt% concentration of about 0.1% to about 99% or any range therein such as, but not limited to, about 1% to about 75% or about 2% to about 30%. In particular embodiments the one or plurality of non-animal-derived hydroxyproline sources are present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 5.75, 6, 6.25, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 8.25, 8.5, 8.75, 9, 9.25, 9.5, 9.75, 10, 10.25, 10.5, 10.75, 11, 11.25, 11.5, 11.75, 12, 12.25, 12.5, 12.75, 13, 13.25, 13.5, 13.75, 14, 14.25, 14.5, 14.75, 15, 15.25, 15.5, 15.75, 16, 16.25, 16.5, 16.75, 17, 17.25, 17.5, 17.75, 18, 18.25, 18.5, 18.75, 19, 19.25, 19.5, 19.75, 20, 21,
22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,
45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67,
68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90,
91, 92, 93, 94, 95, 96, 97, 98, 99 and any range therein. In particularly preferred embodiments, the formulation comprises from about 1 wt% to about 95 wt% of the one or plurality of non-animal-derived hydroxyproline sources.
In view of the above, the formulation suitably includes non- animal-derived hydroxyproline in a wt% concentration of about 0.1% to about 99% or any range therein such as, but not limited to, about 1% to about 75% or about 2% to about 30%. In particular embodiments, non- animal-derived hydroxyproline is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2,
2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 5.75, 6, 6.25, 6.5,
6.75, 7, 7.25, 7.5, 7.75, 8, 8.25, 8.5, 8.75, 9, 9.25, 9.5, 9.75, 10, 10.25, 10.5, 10.75, 11,
11.25, 11.5, 11.75, 12, 12.25, 12.5, 12.75, 13, 13.25, 13.5, 13.75, 14, 14.25, 14.5,
14.75, 15, 15.25, 15.5, 15.75, 16, 16.25, 16.5, 16.75, 17, 17.25, 17.5, 17.75, 18, 18.25,
18.5, 18.75, 19, 19.25, 19.5, 19.75, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,
33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55,
56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78,
79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 and any range therein. In particular embodiments, the formulation comprises from about 1 wt% to about 95 wt% of non- animal-derived hydroxyproline.
Suitably, the formulation of the present aspect is a substantially vegetarian and/or vegan formulation.
As used herein, the term“ vegetarian” refers to a product or formulation, including but not limited to foods and supplements, which are not made from or with the aid of products derived from animals that have died, have been slaughtered, or animals that die as a result of being eaten. Such animals may include farmed, wild or domestic animals, including, but not limited to, livestock poultry, game, fish, shellfish, Crustacea, amphibians, tunicates, echinoderms, molluscs and insects. In one example, a product can be vegetarian if it includes dairy products and eggs.
As used herein, the term“vegan” refers to a product including, but not limited to foods and supplements, which are not made from or with the aid of animals or animal products (including products from living animals).
In one particular embodiment, the formulation of the present aspect is in the form of a supplement, such as a protein supplement. As used herein, the term “ supplement” refers to a supplement intended to supplement a diet of food and water, where the diet is sufficient to support life. A supplement may contain vitamins, minerals, herbs or other botanicals, amino acids, enzymes, organ tissues, glandular metabolites, or combinations thereof. Supplements may be administered by any
convenient means, including parenteral or enteral routes. Enteral routes may include oral, gastric, or subgastric administration, including rectal administration. In a preferred form, the supplements of the present invention are administered orally. As such, the formulation may be in the form of a capsule, a cachet, a pill, a tablet, a powder, a granule, a pellet, a bead, a particle, a troche, a lozenge, and/or a gel.
In another embodiment, the formulation is in the form of a food product. Examples of suitable food products include a bar, such as a cereal or protein bar, a breakfast cereal, such as granola, a cracker, a biscuit and a snack, such as a snack chip. The preparation of these products is well known to the skilled person and does not require further detail here.
In an alternative embodiment, the formulation is a topical formulation. To this end, such a topical formulation of the invention may comprise a pharmaceutically acceptable carrier, diluent or excipient, including, but without limitation thereto, an effective amount of a moisturising, solubilising and/or substantive ingredient. A useful reference describing pharmaceutically acceptable carriers, diluents and excipients is Remington’s Pharmaceutical Sciences (Mack Publishing Co. NJ USA, 1991).
In some embodiments, the formulation has a semi-solid consistency of a mousse, gel, cream, lotion, oil, spray or paint for ease of storage and application. The formulation preferably has the consistency of a cream.
In one embodiment, an effective amount of a thickener may be incorporated within the formulation to obtain the desired viscosity and consistency of the product for example, as use as a cream, lotion or ointment.
In one embodiment, the formulation may be delivered using the following non-limiting examples: carbomer gel, serum, spray, bath oils, massage oils, patches, nanopatches, nanodelivery systems, compresses, poultices, tape, bandages, strapping tape, dose delivery devices, slow release devices, epidermal injection, subcutaneous injection, dropper, clothing, dressings, gauze and/or injection.
Suitably, the further amino acid of the present aspect can be any known in the art, inclusive of essential and non-essential amino acids, as well as derivatives or variants thereof, such as amino acid salts. Nonlimiting examples include leucine, isoleucine, valine, lysine, glutamine, threonine, phenylalanine, methionine, tryptophan, histidine, taurine, arginine, serine, proline, glycine, alanine, ornithine,
citrulline, urocanic acid, asparagine and tyrosine. In particular embodiments, the further amino acid is selected from the group of leucine, isoleucine, valine, lysine, glutamine, threonine, phenylalanine, methionine, tryptophan, histidine, taurine, and any combination thereof.
With respect to the present aspect, the formulation may include one or more further amino acids in addition to hydroxyproline, such as those hereinbefore described, in a wt% concentration of about 0.1% to about 99% or any range therein such as, but not limited to, about 1% to about 35% or about 2% to about 20%. In particular embodiments the further amino acid is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3,
3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 5.75, 6, 6.25, 6.5, 6.75, 7, 7.25, 7.5,
7.75, 8, 8.25, 8.5, 8.75, 9, 9.25, 9.5, 9.75, 10, 10.25, 10.5, 10.75, 11, 11.25, 11.5,
11.75, 12, 12.25, 12.5, 12.75, 13, 13.25, 13.5, 13.75, 14, 14.25, 14.5, 14.75, 15, 15.25, 15.5, 15.75, 16, 16.25, 16.5, 16.75, 17, 17.25, 17.5, 17.75, 18, 18.25, 18.5, 18.75, 19,
19.25, 19.5, 19.75, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 and any range therein. In particularly preferred embodiments, the formulation comprises from about 1 wt% to about 95 wt% of the further amino acid.
As generally used herein, the term " sweetening agent " refers to natural or artificial compounds used to increase the sweetness of the present formulation. It will be appreciated that sweetening agents include carbohydrate sweetening agents, (i.e., sugars and other carbohydrate sweetening agents) and non-carbohydrate sweetening agents. As used here the term "sugar” refers to sucrose and the constituents of sucrose (e.g., glucose and/or fructose, sugar syrup, malt syrup, maple syrup, starch syrup, glucose syrup, high-fructose syrups such as high-fructose corn syrup, honey, molasses) and other carbohydrates that can be used as sweetening agents or a source of these. The term "other carbohydrate sweetening agents" refers to, for example, sugar alcohols, such as xylitol, maltitol, lactitol and sorbitol. Suitable examples of the non-carbohydrate sweetening agents include e.g. stevia, aspartame (phenylalanine), acesulfame potassium (Ace-K), saccharin, cyclamates and sucralose. Accordingly, the sweetener may include a low calorie sweetener, a natural sweetener, a non-nutritive
sweetener and/or an artificial sweetener. Additionally, the sweetener may be naturally or synthetically derived. Suitably, the sweetening agent or combination of sweetening agents are present at a concentration of about 0.01 to about 20 wt%, more preferably about 0.05 to about 10 wt% or even more preferably about 0.1 to about 2 wt%.
The formulation of the invention can include one or more sweetening agents, such as those hereinbefore described, in a wt% concentration of about 0.1% to about 10% or any range therein such as, but not limited to, about 1% to about 5% or about 0.2% to about 2%. In particular embodiments the sweetening agent is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 5.75, 6, 6.25, 6.5,
6.75, 7, 7.25, 7.5, 7.75, 8, 8.25, 8.5, 8.75, 9, 9.25, 9.5, 9.75, 10 and any range therein. In particularly preferred embodiments, the formulation comprises from about 0.5 wt% to about 5 wt% of the sweetening agent.
It will be appreciated that the colouring agent may be any as are known in the art. To this end, a wide range of food grade colouring agents is used by the food industry in order to enhance the optical appearance of food, dietary supplements and the like. Of the known food grade colouring agents, only a few are natural, such as betanoin or chlorophyll, for instance. Most food grade colouring agents are either synthetic analogues of naturally occurring substances - so-called nature identical substances - or are fully artificial.
Further to the above, the formulation of the invention can include one or more colouring agents, such as those hereinbefore described, in a wt% concentration of about 0.1% to about 20% or any range therein such as, but not limited to, about 1% to about 15% or about 2% to about 12%. In particular embodiments the colouring agent is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1,
1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,
5.75, 6, 6.25, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 8.25, 8.5, 8.75, 9, 9.25, 9.5, 9.75, 10,
10.25, 10.5, 10.75, 11, 11.25, 11.5, 11.75, 12, 12.25, 12.5, 12.75, 13, 13.25, 13.5,
13.75, 14, 14.25, 14.5, 14.75, 15, 15.25, 15.5, 15.75, 16, 16.25, 16.5, 16.75, 17, 17.25, 17.5, 17.75, 18, 18.25, 18.5, 18.75, 19, 19.25, 19.5, 19.75, 20 and any range therein. In particularly preferred embodiments, the formulation comprises from about 0.5 wt% to about 5 wt% of the colouring agent.
The flavouring agents of the invention may be any natural or non-natural substance which adds or enhances flavour. The flavouring agents may also comprise natural or non-natural stabilizers, anti-caking and/or flow agents. Flavouring agents are typically comprised of a flavoured substance(s) and complexes manufactured or extracted from nature in liquid or powdered form to impart a particular flavour into a product. Excipients are added to preserve, stabilize and maintain form and colour. Typical excipients may include flow agents, anticaking agents, antioxidants, including but not exclusively, maltodextrin, gum acacia, tapioca starch, propylene glycol and triacetin.
Referring to the present aspect, the formulation may include one or more flavouring agents, such as those hereinbefore described, in a wt% concentration of about 0.1% to about 20% or any range therein such as, but not limited to, about 1% to about 15% or about 2% to about 10%. In particular embodiments the flavouring agent is present at a wt% concentration of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1,
1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,
5.75, 6, 6.25, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 8.25, 8.5, 8.75, 9, 9.25, 9.5, 9.75, 10,
10.25, 10.5, 10.75, 11, 11.25, 11.5, 11.75, 12, 12.25, 12.5, 12.75, 13, 13.25, 13.5,
13.75, 14, 14.25, 14.5, 14.75, 15, 15.25, 15.5, 15.75, 16, 16.25, 16.5, 16.75, 17, 17.25, 17.5, 17.75, 18, 18.25, 18.5, 18.75, 19, 19.25, 19.5, 19.75, 20 and any range therein. In particularly preferred embodiments, the formulation comprises from about 1 wt% to about 10 wt% of the flavouring agent.
In particular embodiments, the formulation of the present aspect further includes a filler, such as those known in the art. It will be appreciated that a filler is an ingredient added to provide bulk or some other non-nutritive purpose to a composition or formulation.
In one embodiment, the formulation further comprises a saponin source including one or more saponins, such as that derived from Astragalus membranaceus and/or Panax notoginseng. In this regard, a preferred saponin source is AstraGin® which contains purified saponins isolated from the Astragalus membranaceus and Panax notoginseng plants.
The term "saponin" as used herein includes glycosidic triterpenoid compounds which produce foam in aqueous solution, have haemolytic activity in most cases, and possess immune adjuvant activity. It will also be appreciated that the term
encompasses the saponin per se, as well as natural and pharmaceutically acceptable salts and pharmaceutically acceptable derivatives thereof. The term "saponin" also encompasses biologically active fragments thereof.
For purposes of this invention, the term“ saponin source" generally refers to any saponin source that is, or can be, obtained or derived from plants or plant parts, including synthetically manufactured saponins. Natural saponins, however, are preferred. In particular embodiments, the saponin source is or comprises a saponin- rich extract or concentrate. It will be appreciated that such saponin-rich extracts or concentrates may be in any form, including liquid and solid forms.
Suitably, the formulation comprises from about 0.1 wt% to about 5 wt% (e.g., about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, and any range therein) of the saponin source. More particularly, the formulation comprises from about 0.1 wt% to about 2 wt% of the saponin source.
Suitably, the formulation of the present aspect further comprises one or more vitamins and/or minerals, such as electrolytes. Exemplary vitamins include vitamin A (e.g., vitamin Ai retinol, axerophthol, a-carotene, b-carotene, g-carotene), B vitamins (e.g., Bi vitamins including: thiamin, aneurin, thiamine, pyrophosphate, cocarboxylase; B2 vitamins including riboflavin, vitamin G, lactoflavin, hepatoflavin, ovoflavin, verdoflavin, riboflavin mononucleotide, FMN, riboflavin dinucleotide, FAD; Vitamin B3 (niacin), Vitamin Be (pyridoxine, pyridoxal-5-phosphate), Vitamin B7 (biotin), Vitamin B12 (cobalamin, methylcobalamin)), Vitamin C (ascorbic acid, antiscorbutic vitamin, dehydroascorbic acid), D vitamins (antirachitic vitamin, vitamin D2, D3, cholecalciferol, etc), Vitamin E, Vitamin K, and the like. Nonlimiting examples of minerals include sodium, selenium, zinc, magnesium, calcium, iron, manganese, copper, chromium, phosphorous, iodine, potassium and molybdenum.
As used herein,
concentration”, unless otherwise specified, may refer to percent weight/volume (w/v), percent weight/weight (w/w) or percent volume/volume (v/v) of a particular ingredient within the formulation as applicable.
The terms“ component” and“ derivative” refer to any product/s which may be derived using a downstream processing technique or techniques (e.g. a series of techniques) known in the art, such as extraction and purification techniques.
In some embodiments, the formulation further comprises a pH modifier. The pH modifier may be any agent, substance or molecule that facilitates obtaining and/or maintaining an optimal pH for the formulation. The pH modifier may be a buffering agent, acid or base that facilitates achieving an acidic pH, an alkaline pH or neutral pH (i.e., about pH 7). Typically, the pH modifier is an acid, such as an organic acid. Organic acids may be any food acid, such as a carboxylic acid, that is suitable for human consumption and includes salts of said organic acids. Non-limiting examples include tartaric acid, citric acid, lactic acid, benzoic acid, acetic acid, malic acid, ascorbic acid, succinic acid, fumaric acid, oxalic acid and their salts (e.g tartrates, citrates, lactates etc). Preferred organic acids are citric acid, malic acid and ascorbic acid.
Suitably, the pH modifiers are present at a concentration of about 1-10% (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 wt% or any range therein) by weight in total, or preferably about 2-7% by weight in total. In an embodiment, malic acid and/or citric acid is present at about up to 7.0% by weight of the formulation.
Further to the above, the formulation of the present aspect, inclusive of topical and orally administrable formulations, may include one or more natural ingredients or extracts (inclusive of plant extracts and algal extracts), such as those that can serve as effective ingredients for reducing undesirable traits associated with aging and/or compounds for facilitating wound care in different skin care applications. Non limiting examples of such natural ingredients include fucoidan or extracts thereof, Moringa oleifera or extracts thereof, Aloe or extracts thereof, soy or extracts thereof, Cyathea medularis or extracts thereof, Centipeda cunninghamii or extracts thereof, Phyllanthus emblica or extracts thereof, Aphanizomenon flos-aquae or extracts thereof, Chlorella vulgaris or extracts thereof, Broccoli ( Brassica oleracea var. italica ) or extracts thereof, Chia (e.g., Salvia hispanica, Salvia columbariae), inclusive of Chia seeds, or extracts thereof, bamboo or extracts thereof, Punica granatum or extracts thereof, Croton lechleri or extracts thereof, colostrum or extracts thereof, Citrus aurantium or extracts thereof, Lonicera japonica or extracts thereof, Olea europaea or extracts thereof, Polypodium leucotomos or extracts thereof, Camellia sinensis or extracts thereof, Aristotelia chilensis or extracts thereof, berries or extracts thereof, Theobroma cacao or extracts thereof, Cocos nucifera or extracts thereof (inclusive of coconut water powder), Vitellaria nilotica or extracts thereof,
Rosa rubiginosa or extracts thereof, Ceteryl olivate or extracts thereof, Theobroma cacao or extracts thereof, Glycine max or extracts thereof, Citrus sinensis or extracts thereof, Quillaja saponaria or extracts thereof, Helianthus annuus or extracts thereof, NAG6P, E. coli or extracts thereof, Rosa damascena or extracts thereof, Jasminum grandiflorum or extracts thereof, Cananga odorata or extracts thereof, Citrus reticulata or extracts thereof, and/or Vanilla or extracts thereof.
In one particular embodiment of the present aspect, the formulation is a supplement formulation comprising:
(i) non- animal-derived hydroxyproline;
(ii) a further amino acid, such as glycine, proline, alanine and any combination thereof;
(iii) a vitamin, such as vitamin A, vitamin Bi, vitamin B2, vitamin B3, vitamin Be, vitamin B7, vitamin B12, vitamin C, vitamin D3, vitamin E and any combination thereof; and
(i) optionally one or more natural extracts, such as those hereinbefore described.
In a further aspect, the invention provides a method of producing the formulation according to the aforementioned aspect, including the step of combining the non-animal-derived hydroxyproline and/or one or more components or derivatives thereof with the further amino acid, the vitamin, the mineral, the natural extract, the sweetening agent, the colouring agent, the flavouring agent and/or the pharmaceutically acceptable carrier, diluent and/or excipient to thereby produce the formulation.
The method of the present aspect suitably preserves the ability of the hydroxyproline to, for example, promote collagen synthesis and/or treat a hydroxyproline deficiency or a disease, disorder or condition associated therewith. By way of example, preserving these properties may be achieved by avoiding exposing the formulation to excessive heat. As such, combining the ingredients of the formulation at room temperature may improve the efficacy thereof.
In a related aspect, the invention provides a formulation produced according to the aforementioned aspect.
In another aspect, the invention provides a formulation described herein, for use in:
(i) promoting collagen production; and/or
(ii) the therapeutic and/or prophylactic treatment of a hydroxyproline deficiency;
in a subject.
Suitably, the hydroxyproline deficiency is characterised by one or more of collagen deficiency, gastrointestinal dysfunction, arthritis, osteoarthritis, wrinkles, premature ageing, chronic fatigue syndrome, fibromyalgia, pain, recurrent injuries.
In yet another aspect, the invention provides a method of promoting collagen production in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation described herein, to thereby promote collagen production in the subject.
By “administration” or “administering” is meant the introduction of a formulation (e.g., a formulation comprising, consisting or consisting essentially of a non- animal-derived hydroxyproline source, and one or more of a further amino acid, a sweetening agent, a colouring agent, a flavouring agent, a vitamin, a mineral, a natural extract and/or a pharmaceutically acceptable carrier, diluent and/or excipient) into a subject by a chosen route, and in particular by the oral and/or topical route.
The term “therapeutically effective amount” describes a quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent. For example, this can be the amount of the formulation hereinbefore described to: (a) promote collagen production; and/or (b) reduce, alleviate and/or prevent a disease, disorder or condition associated with the hydroxyproline deficiency. In some embodiments, a“therapeutically effective amount” is sufficient to reduce or eliminate a symptom of such a disease, disorder or condition. In other embodiments, a“therapeutically effective amount” is an amount sufficient to achieve a desired biological effect, for example an amount that is effective to promote collagen production in a subject with the hydroxyproline deficiency.
Ideally, a therapeutically effective amount of an agent is an amount sufficient to induce the desired result without causing a substantial cytotoxic effect in the subject. The effective amount of the formulation useful for, for example, reducing, alleviating and/or preventing a disease, disorder or condition associated with a hydroxyproline deficiency will be dependent on the subject being treated, the type and
severity of any associated disease, disorder and/or condition, and the manner of administration of the therapeutic composition.
In one embodiment, a given dosage of the formulation, such as orally or topically, is applied as a single application or a plurality of applications over a given time period ( e.g ., for as long as the subject requires treatment), where the dosing schedule is administered over a given time period, examples of which include hourly, daily, weekly, biweekly or monthly dosing schedules.
It would also be appreciated that one or more additional agents as are known in the art for reducing, alleviating and/or preventing a disease, disorder and/or condition associated with hydroxyproline deficiency, or one or more symptoms associated therewith, may be administered to a subject in need thereof in addition to a therapeutically effective amount of the formulation described herein. That is, one or more additional agents traditionally used for the treatment and/or prevention of a disease, disorder and/or condition associated with hydroxyproline deficiency, such as an anti-inflammatory agent, may be administered to a subject in addition to a therapeutically effective amount of the formulation.
Any safe route of administration may be employed for providing a subject with a formulation of the present aspect. For example, oral, rectal, parenteral, sublingual, buccal, intravenous, intra-articular, intra-muscular, intra-dermal, subcutaneous, inhalational, intraocular, intraperitoneal, intracerebroventricular, transdermal, and the like may be employed. Most preferably, the formulation is orally and/or topically (i.e., transdermally) administered.
Dosage forms include powder, tablets, dispersions, suspensions, injections, solutions, syrups, troches, capsules, suppositories, aerosols, transdermal patches, liquid drops, diluted in beverage, gum, confectionary, oral strips, gel, jelly, and the like. These dosage forms may also include injecting or implanting controlled releasing devices designed specifically for this purpose or other forms of implants modified to act additionally in this fashion.
The above formulations may be administered in a manner compatible with the dosage formulation, and in such amount as is pharmaceutically/therapeutically- effective. The dose administered to a subject, in the context of the present invention, should be sufficient to effect a beneficial response (e.g., a reduction or amelioration in symptoms of a disease, disorder or condition associated with hydroxyproline
deficiency) in a subject over an appropriate period of time. The quantity of the formulation to be administered may depend on the subject to be treated, inclusive of the age, sex, weight and general health condition thereof, factors that will depend on the judgement of a practitioner of ordinary skill in the art.
In a related aspect, the invention provides a method of treating and/or preventing a hydroxyproline deficiency in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation described herein, to thereby treat and/or prevent said hydroxyproline deficiency in the subject.
As used herein, “ treating “treat” or“ treatment” refers to a therapeutic intervention, course of action or protocol that at least ameliorates a symptom of a disease, disorder or condition associated with the hydroxyproline deficiency after said disease, disorder or condition and/or its symptoms have at least started to develop. As used herein, “preventing” , “ prevent” or “ prevention” refers to therapeutic intervention, course of action or protocol initiated prior to the onset of a disease, disorder or condition associated with the hydroxyproline deficiency and/or a symptom thereof so as to prevent, inhibit or delay or development or progression of said disease, disorder or condition or the symptom. In this regard, a“ prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of a disease, disorder or condition associated with hydroxyproline deficiency or exhibits only early signs for the purpose of decreasing the risk of developing such a disease, disorder or condition.
It will be appreciated that the hydroxyproline deficiency may be characterised by one or more diseases, disorders or conditions as are known in the art. In particular embodiments, the hydroxyproline deficiency is characterised by one or more of collagen deficiency, gastrointestinal dysfunction, arthritis, osteoarthritis, wrinkles, premature ageing, chronic fatigue syndrome, fibromyalgia, pain, and recurrent injuries. To this end, it will be appreciated that hydroxyproline is a major component of the protein collagen. Hydroxyproline and proline play key roles for collagen stability. Defects in collagen synthesis lead to easy bruising, internal bleeding, breakdown of connective tissue of the ligaments and tendons, and increased risk to blood vessel damage. Increased spill of hydroxyproline in the urine is generally associated with breakdown of connective tissue due to a disease process and may also
be a manifestation of vitamin C deficiency. Deficiency of hydroxyproline is only known to occur if there is a deficiency of vitamin C.
The term “ subject”, as used herein, includes both human and veterinary subjects. For example, administration to a subject can include administration to a human subject or a veterinary subject. Preferably, the subject is a human. However, therapeutic uses according to the invention may also be applicable to mammals such as domestic and companion animals, performance animals such as horses, livestock, and laboratory animals.
All computer programs, algorithms, patent and scientific literature referred to herein is incorporated herein by reference.
So that the present invention may be more readily understood and put into practical effect, the skilled person is referred to the following non-limiting examples.
EXAMPLE 1
Example 1 provides an embodiment of the formulation as a dietary protein supplement.
Ingredient _ Amount
EXAMPLE 2
Example 2 provides a further embodiment of the formulation as a dietary protein supplement.
Ingredient _ Amount
EXAMPLE 3
Example 3 provides an embodiment of the formulation of the invention as an oral capsule designed as a cosmetic or beauty product to promote collagen production. In this regard, the two powdered ingredients each at 250 mg are mixed together to make 500mg, which is subsequently encapsulated into a vegan capsule with optionally a suitable amount of a natural excipient, flow agent or filler.
Ingredient _ Amount
Amla (Phyllanthus emblica) water extract standardised 250mg to ascorbate (or seabuckthorn fruit extract)
Hydroxyproline 250mg
Claims
1. A formulation comprising, consisting or consisting essentially of:
(i) non- animal-derived hydroxyproline and/or one or more components or derivatives thereof; and
(ii) one or more of a further amino acid, a sweetening agent, a colouring agent, a flavouring agent, a vitamin, a mineral, a natural extract and/or a pharmaceutically acceptable carrier, diluent and/or excipient.
2. The formulation of Claim 1, wherein the formulation is a substantially vegetarian and/or vegan formulation.
3. The formulation of Claim 1 or Claim 2, wherein the non-animal-derived hydroxyproline is or comprises L-hydroxyproline.
4. The formulation of any one of the preceding claims, wherein the non-animal- derived hydroxyproline is or comprises a bacteria-derived hydroxyproline source, an algae-derived hydroxyproline source and/or a plant-derived hydroxyproline source.
5. The formulation of Claim 4, wherein the plant-derived hydroxyproline source is or comprises a corn-derived hydroxyproline source and/or a moss-derived hydroxyproline source.
6. The formulation of any one of the preceding claims, wherein the further amino acid is selected from the group of glycine, proline, alanine, leucine, isoleucine, valine, lysine, glutamine, threonine, phenylalanine, methionine, tryptophan, histidine, taurine, and any combination thereof.
7. The formulation of any one of the preceding claims, wherein the formulation comprises from about 1 wt% to about 99 wt% of the non-animal-derived hydroxyproline.
8. The formulation of any one of the preceding claims, wherein the formulation comprises from about 1 wt% to about 95 wt% of the further amino acid.
9. The formulation of any one of the preceding claims, wherein the formulation comprises from about 0.5 wt% to about 5 wt% of the sweetening agent.
10. The formulation of any one of the preceding claims, wherein the formulation comprises from about 0.5 wt% to about 5 wt% of the colouring agent.
11. The formulation of any one of the preceding claims, wherein the formulation comprises from about 1 wt% to about 10 wt% of the flavouring agent.
12. The formulation of any one of the preceding claims, further comprising a saponin source.
13. The formulation of Claim 12, wherein the saponin source is derived from Astragalus membranaceus and/or Panax notoginseng.
14. The formulation of Claim 13, wherein the formulation comprises from about 0.1 wt% to about 2 wt% of the saponin source.
15. The formulation of any one of the preceding claims, wherein the formulation is in the form of a supplement.
16. The formulation of Claim 15, wherein the formulation is a protein supplement.
17. The formulation of any one of the preceding claims, wherein the formulation is in the form of a food product.
18. The formulation of any one of Claims 1 to 14, wherein the formulation is in the form of a topical formulation.
19. The formulation of any one of the preceding claims, comprising:
(i) non- animal-derived hydroxyproline;
(ii) a further amino acid;
(iii) a vitamin and/or a mineral; and
(iv) optionally one or more natural extracts.
20. A method of producing the formulation according to Claims 1 to 19, including the step of combining the non- animal-derived hydroxyproline and/or one or more components or derivatives thereof with the further amino acid, the sweetening agent, the colouring agent, the flavouring agent, the vitamin, the mineral, the natural extract and/or the pharmaceutically acceptable carrier, diluent and/or excipient to thereby produce the formulation.
21. A formulation produced according to the method of Claim 20.
22. A formulation according to the any one of Claims 1 to 19 and 21, for use in:
(i) promoting collagen production; and/or
(ii) the therapeutic and/or prophylactic treatment of a hydroxyproline deficiency;
in a subject.
23. A method of promoting collagen production in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation according to any one of Claims 1 to 19 and 21, to thereby promote collagen production in the subject.
24. A method of treating and/or preventing a hydroxyproline deficiency in a subject, said method including the step of administering to said subject a therapeutically effective amount of the formulation according to any one of Claims 1 to 19 and 21, to thereby treat and/or prevent said hydroxyproline deficiency in the subject.
25. The use of Claim 22 or the method of Claim 24, wherein the hydroxyproline deficiency is characterised by one or more of collagen deficiency, gastrointestinal
dysfunction, arthritis, osteoarthritis, wrinkles, premature ageing, chronic fatigue syndrome, fibromyalgia, pain and recurrent injuries.
26. The method or use according to any one of Claims 22 to 25, wherein the subject is a human.
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AU2018904658A AU2018904658A0 (en) | 2018-12-07 | Formulation and method of use | |
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AU2019101234A AU2019101234B4 (en) | 2018-12-07 | 2019-10-09 | Formulation and method of use |
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