Collagen peptide mouth spray for oral use in the mouth

Abstract

Oral spray for the oromucosal administration of collagen peptides with an average molecular weight of 300 to 800 Dalton.

Description

Technical area

[0001] The invention relates to the biomedical and cosmetic application of low-molecular-weight collagen peptides for absorption through the oral mucosa via a spray. It serves, in particular, to improve bioavailability, connective tissue, skin health, and joint health through targeted drug delivery. State of the art

[0002] Collagen peptides are short amino acid sequences obtained by hydrolysis of collagen. Typically, collagen hydrolysates consist of mixtures of different peptide lengths (e.g., di- and tripeptides from -300-800 Da to oligopeptides >2000 Da). Low-molecular-weight peptides (-500 Daltons) are particularly interesting because it is generally accepted that molecules below -500 Da can more easily cross biological barriers. Studies suggest that such smaller peptides, when ingested orally, can improve skin hydration, increase elasticity, and reduce wrinkles. These effects are attributed to the fact that absorbed collagen fragments reach the skin's connective tissue, where they serve as building blocks and, as signaling peptides, stimulate the synthesis of new dermal collagen.

[0003] Conventional collagen supplements are absorbed orally through the digestive tract, with the peptides being partially degraded by digestive enzymes and stomach acid. The absorbable portion varies greatly and is limited.

[0004] The oromucosal route offers the possibility of transferring bioactive substances directly into the systemic circulation and bypassing metabolic degradation pathways and can thus offer advantages over conventional gastrointestinal administration, for example through faster absorption or higher bioavailability of intact peptides. Subject of the invention

[0005] The invention relates to an oral spray containing collagen peptides with an average molecular weight of less than 500 Daltons. The small molecular size enables absorption through the mucosa of the oral cavity (sublingual or buccal). Absorption occurs primarily via the veins of the oral region (sublingual vein, facial vein) and enters the systemic bloodstream, thereby achieving rapid and efficient distribution throughout the body—particularly into the extracellular matrix system of the skin (dermis), i.e., into the skin's connective tissue, or even into the cartilage connective tissue of the joints. Justification for the novelty

[0006] Currently, the market primarily offers orally administered collagen preparations in the form of powders, drinks, tablets, or capsules. These products rely on gastrointestinal absorption of the peptides and are therefore subject to hepatic first-pass metabolism, which reduces bioavailability. Collagen products in the form of oral sprays are not yet available in formulations explicitly designed for oromucosal absorption of small collagen peptides (≤800 Da). Oromucosal application (e.g., as a spray, sublingual, or buccally) is already known and commercially available for vitamins and other micronutrients, for example, but not yet for the absorption of collagen and collagen peptides. Technological progress

[0007] With oromucosal application (e.g., as a spray, sublingual, or buccal), the active ingredient is released in the oral cavity and diffuses directly through the mucosa into the bloodstream. This route bypasses the gastrointestinal tract and the liver's first-pass effect (at least partially, since the oral veins drain into the superior vena cava). Advantages include faster absorption and avoidance of enzymatic degradation in the intestine.

[0008] Characteristic of this path are: • Transcellular and paracellular diffusion of small peptides through the mucosa. • Fast absorption due to good blood flow to the mucous membrane. • Direct bypassing of gastrointestinal degradation (e.g. by peptidases). • Transport to target tissues such as the skin via the bloodstream.

[0009] The mechanism of action in the target tissue is • stimulation of fibroblasts for endogenous collagen synthesis • Improvement of dermal structure, elasticity and hydration • Reduction of fine lines and wrinkles • Improvement of articular cartilage structure

[0010] To compare the bioavailability of the two routes, oral mucosa vs. intestine, the following hypothesis is put forward based on analogous studies: • Peptides with <500 Da are considered to be absorbable via the sublingual mucosa (cf. [Shojaei, J Pharm Pharm Sci]). • Comparative studies for other peptides (e.g. insulin analogues or vasopressin) show up to 10 times faster plasma concentration via the oral mucosa. • Assumption: Increased bioavailability and faster absorption because: ◯ no enzymatic hydrolysis in the stomach / intestine ◯ no first-pass degradation in the liver ◯ more complete peptide profile in the target tissue

[0011] This results in the following estimate of bioavailability: Recording path Bioavailability estimated Special features Gastrointestinal approx. 10-15% Enzymatic decomposition, liver first pass Oromucosal (spray) approx. 30-50% (extrapolated) Fast, enzyme-free, direct blood contact

[0012] In addition to bioavailability, one advantage is the speed of absorption: A major benefit of the oromucosal route of administration is its very rapid absorption, provided the substance is permeable. Drugs that easily penetrate the oral mucosa often reach effective plasma levels within minutes. There are no direct measurements of the Tmax (time to maximum concentration) for collagen peptides via the oral mucosa, but one can extrapolate: With immediate diffusion into the capillary network under the tongue, a peak could occur after as little as 15-30 minutes, significantly faster than the ~1-2 hours with gastrointestinal absorption. This means that a collagen oral spray could achieve a faster onset effect, i.e., cause a steep concentration peak, which is more effective as a signaling stimulus for fibroblasts, for example. With conventional oral administration, peptide levels tend to be more widely distributed over several hours, which is more consistent with a continuous supply of nutrients.Whether a rapid onset effect leads to stronger effects (e.g. stronger collagen synthesis stimulation) is currently speculative - but it is conceivable that higher short-term dipeptide concentrations in the blood trigger certain signaling pathways more strongly.

[0013] This invention represents a novel delivery system for the improved utilization of bioactive peptides. The combination of low molecular mass and oromucosal absorption creates an effective alternative to traditional oral collagen intake with potentially higher efficacy.

[0014] Sources: • Shojaei, A.H. (1998). Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharm Sci, 1(1), 15-30. • Proksch, E. et al. (2014). Oral supplementation of specific collagen peptides improves skin physiology: a double-blind, placebo-controlled study. Skin Pharmacol Physiol, 27(1), 47-55. • Yazaki, M. et al. (2017). Collagen peptide ingestion improves skin hydration and elasticity. J Sci Food Agric, 97(9), 3066-3071. • Czajka, A. et al. (2018). Collagen hydrolysate for skin aging: a literature review. J Med Food, 21(10), 1001-1009. QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited non-patent literature

[0000] Shojaei, A. H. (1998). Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharm Sci, 1(1), 15-30

[0014] Proksch, E. et al. (2014). Oral supplementation of specific collagen peptides improves skin physiology: a double-blind, placebo-controlled study. Skin Pharmacol Physiol, 27(1), 47-55

[0014] Yazaki, M. et al. (2017). Collagen peptide ingestion improves skin hydration and elasticity. J Sci Food Agric, 97(9), 3066-3071

[0014] Czajka, A. et al. (2018). Collagen hydrolysate for skin aging: a literature review. J Med Food, 21(10), 1001-1009

[0014]

Claims

[1] Oral spray for the oromucosal administration of collagen peptides with an average molecular weight of 300 to 800 Dalton. [2] Oral spray according to claim 1, wherein the collagen peptides are derived from the source fish [3] Oral spray according to claim 1, wherein the collagen peptides are derived from the fish source cod (especially Gadus morhua) [4] Oral spray for the oromucosal administration of collagen peptides, the collagen peptides consisting of collagen tri-peptides [5] Oral spray according to claim 1, wherein the collagen peptides are derived from the source bovine [6] Oral spray according to claim 1, wherein the collagen peptides are derived from the source porcine [7] Oral spray according to claim 1, wherein the collagen peptides are from the chicken (avian) source [8] Oral spray according to claim 1, wherein the collagen peptides are derived from biotechnologically synthetic production from recombinant amino acid sequences [9] Oral spray according to claim 1, which additionally contains elastin peptides. [10] Oral spray according to claim 1, which additionally contains elastin peptides with an average molecular weight of 100 to 1000 Dalton. [11] A mouth spray according to any one of the preceding claims, wherein the spray comprises glycerin, ethanol, buffer systems and flavoring. [12] Use of the oral spray to improve skin physiology by increasing dermal collagen synthesis. [13] Use of the oral spray to improve joint physiology by increasing collagen synthesis in the joint, articular cartilage and cartilage connective tissue. [14] Oral spray according to claims 1 to 12, wherein the collagen peptides have an average molecular weight of less than 300 Da