A lutein composition

Abstract

A micronutrient composition for infants and children from 6 months of age, characterized in that it is a liquid oral formulation containing the following main active ingredients: microencapsulated lutein, microencapsulated zeaxanthin, proanthocyanidins, anthocyanins, taurine, zinc, vitamin A and vitamin E, wherein the composition serves to support healthy retinal development in infants, to relieve visual fatigue and to build an antioxidant defense system in the eye.

Description

Technical field

[0001] This invention relates to a trace element supplement with eye-health-promoting ingredients that can support eye development and protect the eye health of infants and children. The trace element supplement may contain lutein, zeaxanthin, taurine, zinc, anthocyanins, proanthocyanidins, vitamin A, and vitamin E. Background technology

[0002] Lutein is a dietary carotenoid that accumulates preferentially in the eyes and brain during early childhood and throughout life. The accumulation of lutein in areas of high metabolism and oxidative stress, such as the eyes and brain, suggests a special role for this component in organ development and maturation.

[0003] Lutein and zeaxanthin are found in cell membranes and can protect cells from oxidative damage through their antioxidant and light-absorbing properties. This is particularly important for eye and brain tissue, especially in early childhood and premature infants. Prematurity increases the risk of oxidative stress. Administering lutein (often in combination with zeaxanthin) is beneficial for premature infants because lutein is a potent antioxidant that can reduce oxidative stress and promote brain and eye development. It may decrease the severity of retinopathy of prematurity (ROP) and improve vision.

[0004] Lutein has been shown to modulate inflammatory responses in the retina, brain, skin and immune cells.

[0005] Lutein and zeaxanthin possess the unique ability to absorb high-energy, short-wavelength visible light (blue light). They not only protect photoreceptor cells from the effects of blue light-induced reactive oxygen species (ROS), but can also positively influence visual function by reducing chromatic aberration and glare, as well as improving contrast sensitivity.

[0006] Studies have also shown that, in addition to its positive effects on eyesight, taking lutein and zeaxanthin can also promote the cognitive abilities of children.

[0007] Infants naturally receive lutein through breast milk and subsequent formula. Exclusive breastfeeding is recommended for at least six months. If exclusive breastfeeding is not possible, infant formula should be introduced. In most parts of the world, this bioactive substance is not included in infant formula. In Europe, lutein is not added to infant formula. This is a significant difference in the composition of breast milk and infant formula and can lead to lower lutein levels in the blood plasma of formula-fed infants. All dark green leafy vegetables are rich in lutein. In 2017, more than one-third of the European population did not consume enough fruit and vegetables. Data from the 2003-2004 NHANES study showed that children and adolescents (1-18 years) consumed less than 0.6 mg of lutein and zeaxanthin per day.It is difficult to obtain these nutrients daily through diet alone, especially during childhood. Therefore, giving additional nutritional supplements to infants and toddlers can fill this gap.

[0008] US11173133B2 concerns the use of the carotenoid pigment zeaxanthin and at least two other ophthalmic nutrients selected from alpha-lipoic acid, omega-3 fatty acids, plant compounds, taurine, carnitine, coenzyme Q10, carnosine and glutathione-stimulating nutrients, for the promotion of ocular health, especially for the prevention or treatment of macular degeneration.

[0009] US7282225B1 relates to a dietary supplement composition containing vitamins, minerals, carotenoids, antioxidants and natural plant extracts for the prevention of retinal diseases and associated visual impairments.

[0010] EP2138055B1 concerns a formulated food containing lutein, zeaxanthin, zinc, and selenium, which has a positive effect on eye health, particularly on improving visual perception in the human eye. It also contributes to the relief of eye fatigue and the improvement of symptoms of visual impairment.

[0011] US20070166354A1 discloses an infant formula containing DHA, lutein and zeaxanthin and a method for using this formula to promote retinal health and visual development in infants, including reducing the severity or risk of retinopathy of prematurity.

[0012] The existing literature focuses either on the prevention or improvement of age-related retinal diseases or on infant formula with added lutein. Currently, there is no specific approach to supplementing inadequate lutein intake in the daily diet of infants and children to promote visual development and protect early childhood eye health. Usable model contents

[0013] To address the aforementioned problems, this invention provides a trace element supplement containing lutein, zeaxanthin, taurine, zinc, vitamin A, vitamin E, anthocyanins, and proanthocyanidins. This supplement promotes eye development in infants and children and protects eye health. In particular, it increases macular pigment density (MPOD), promotes retinal development in infants and children, improves macular protection, and alleviates premature eye strain.

[0014] Lutein and zeaxanthin are the only two dietary carotenoids that form macular pigment in the retina. They selectively accumulate in high concentrations in the fovea of ​​the retina, where they form macular pigment. This pigment acts like "built-in sunglasses" by effectively filtering high-energy blue light (absorption maximum at approximately 460 nm), which can potentially damage the photoreceptor cells of the retina, and by neutralizing light-induced free radicals. This protects the retina from photo-oxidative damage. For infants and young children, sufficient macular pigment density is crucial for the normal development of visual functions, including visual acuity, contrast sensitivity, and processing speed. Mesocecin is a stereoisomer of lutein that is converted in the retina, is particularly abundant in the fovea of ​​the macula, and is an important component of functional macular pigment.To improve the low solubility and instability of lutein and zeaxanthin, ultrafine milling and microencapsulation techniques can solve the dispersion and stability problems of fat-soluble components in aqueous liquids, thereby increasing absorption rates.

[0015] In this invention, lutein and zeaxanthin are microencapsulated. Lutein and zeaxanthin crystals are processed by ultrafine milling into particles with a D90 particle size of less than 5 micrometers. They are then sheared and emulsified to obtain a homogeneous emulsion. The emulsion is then dried into a powder by high-pressure homogenization and spray drying. The advantages of this technology are: High stability: The double protection provided by "crystal oil suspension + microcapsules" significantly reduces the oxidative loss of lutein and zeaxanthin during storage. Good dispersibility: The microencapsulated powder disperses excellently in cold water and is therefore ideally suited for liquid dosage forms. Improved bioavailability: The ultra-fine grinding technology reduces the crystal particle size to the micrometer range, making it easier for the human body to absorb the product (especially in young children with a developing digestive system).

[0016] Proanthocyanidins are highly bioactive, naturally occurring polyphenols with excellent antioxidant properties and the ability to neutralize free radicals. In the eye, proanthocyanidins can improve ciliary muscle microcirculation and alleviate ciliary muscle spasms caused by close-up vision (e.g., when looking at picture books or videos). This helps reduce eye strain and fatigue. At the same time, their strong antioxidant effect protects retinal ganglion cells from damage caused by oxidative stress, thus contributing to the health of retinal neurons.

[0017] Anthocyanins are water-soluble flavonoid pigments. Many fruits and vegetables are rich in anthocyanins, which possess strong antioxidant and anti-inflammatory properties. One cause of myopia in children is excessive contraction of the ciliary muscle during near vision, leading to spastic refractive errors of the lens. Studies have shown that anthocyanins from blackcurrants have a ciliary muscle-relaxing effect. The mechanisms mediated by endothelin B receptors and the NO / cGMP signaling pathway may be related. A number of double-blind, placebo-controlled crossover studies in humans have confirmed that blackcurrant consumption can improve dark adaptation and a temporary myopic shift in refractive state. Therefore, anthocyanins from blackcurrants have the potential to protect eye health in early childhood.

[0018] Taurine is one of the most abundant free amino acids in the human body and plays a particularly important role in the development and function of the retina. In the retina, taurine is present in high concentrations in photoreceptor cells and retinal pigment epithelial cells, fulfilling a variety of physiological functions such as regulating osmotic pressure, stabilizing membranes, providing antioxidant effects, and regulating calcium ion homeostasis. For infants and young children, taurine is considered a "conditionally essential amino acid" because the body can only synthesize limited amounts of it and therefore it must be obtained from external sources (such as breast milk and infant formula) to ensure the normal development of the central nervous system and the retina. Taking taurine supplements helps protect retinal neurons and can alleviate visual fatigue.

[0019] Zinc is an essential trace element for maintaining eye health. It is present in extremely high concentrations in the retina and is a cofactor for many enzymes of the visual cycle (such as retinol dehydrogenase). It plays a crucial role in the conversion of vitamin A to its active form and is involved in the synthesis of the visual pigment rhodopsin. Sufficient zinc is essential for maintaining dark adaptation and protecting retinal pigment epithelial (RPE) cells from oxidative damage. The zinc glycinate selected in this invention is an organically chelated zinc preparation that, compared to conventional zinc sulfate or zinc oxide, exhibits higher bioavailability and causes less gastrointestinal irritation in infants.

[0020] Vitamin A is a major component of the light-sensitive substance rhodopsin in photoreceptor cells and is essential for normal vision in the dark and for color vision. Vitamin A deficiency is a leading cause of night blindness and dry eyes in young children and increases susceptibility to infections, seriously affecting their growth, development, and survival. Adequate vitamin A intake is fundamental for the function of retinal photoreceptor cells and the integrity of the conjunctival epithelium in young children.

[0021] Vitamin E (mainly α-tocopherol) is the most important fat-soluble antioxidant in the human body. It is incorporated into the cell membrane, effectively scavenging and neutralizing free radicals, interrupting the lipid peroxidation chain reaction, and protecting the polyunsaturated fatty acids in the extracellular segment of retinal photoreceptor cells from oxidative stress. In this invention, vitamin E and lutein work synergistically to form a protective system against photooxidative damage.

[0022] As is known, the dosage for infants must be determined with particular care. The dosage range described in this invention has been carefully established based on weight, developmental stage, and existing safety data for children from 6 months of age. The exact dosage can be individually adjusted under medical or nutritional guidance.

[0023] Preferred embodiments are listed below: According to the present invention, the daily dosage of the micronutrient combination preparation is: 1-20 mg lutein, 0.2-4 mg zeaxanthin, 1-200 mg anthocyanins, 1-100 mg proanthocyanidins, 10-300 mg taurine, 0.5-7 mg zinc, 1-430 µg vitamin A, and 1-9 mg vitamin E. The preferred dosage form of the product is an oral liquid solution, and the preferred packaging form is individually wrapped blister strips. Detailed implementation scheme

[0024] Exemplary embodiments of the present invention are listed below. Example 1: Preferred formulation of a liquid oral solution (single dose, approx. 10 ml) Lutein (microencapsulated, from calendula extract): Equivalent to 6 mg lutein Zeaxanthin (microencapsulated, from calendula extract): Equivalent to 1.2 mg zeaxanthin (with a meso-zeaxanthin content of ≥ 1.02 mg) SuperVision® Fruit Extract: 25 mg Proanthocyanidins (from grape seed extract): 14.75 mg Anthocyanins (from blackcurrant extract): 2 mg Taurine: 15 mg Zinc (zinc glycinate, Albion®): Equivalent to 1 mg zinc Vitamin A (e.g. retinyl acetate or retinyl palmitate): 150 µg Vitamin E (e.g. dl-α-tocopherol acetate): 4 mg Excipients: Purified water, sugar alcohol, pectin, citric acid, sodium citrate, flavorings, etc., approx. 10 ml. Example 2: Another possible liquid oral solution (single dose, approx. 10 ml) Lutein (microencapsulated): 1-20 mg Zeaxanthin (microencapsulated): 0.2-4 mg Proanthocyanidins (grape seed extract): 1-100 mg Anthocyanins (blackcurrant): 1-200 mg Taurine: 10-300 mg Zinc (zinc glycine): 0.5-7 mg Vitamin A: 1-430 µg Vitamin E: 1-9 mg Auxiliary materials as needed. Example 3: Powder dosage form (single dose, for dissolution and oral administration) The liquid formulation from Example 1 is processed into a powder by spray drying or other methods and filled into blister strips. Its active ingredient composition is the same as that of Example 1. Quotes in the description

[0025] This list of documents provided by the applicant is automatically generated and is for informational purposes only. Cited patent documents US11173133B2

[0008] US7282225B1

[0009] EP2138055B1

[0010] US20070166354A1

[0011] Cited non-patent literature

[0026] Giampietri M, Lorenzoni F, Moscuzza F, Boldrini A, Ghirri P. Lutein and neurodevelopment in preterm infants. Front Neurosci. 2016 Sep 7;10:411. doi: 10.3389 / fnins.2016.00411. PMID: 27656124; PMCID: PMC5013125.

[0003]

[0027] Johnson EJ. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr Rev. 2014 Sep;72(9):605-12. doi: 10.1111 / nure.12133. Epub 2014 Aug 8. PMID: 25109868.

[0028] EUROSTAT. Do You Eat Fruit and Vegetables Daily? Available online: https: / / ec.europa.eu / eurostat / web / products-eurostat-news / - / DDN-20190401-1

[0007] Johnson, E.J.; Maras, J.E.; Rasmussen, H.M.; Tucker, K.L. Intake of Lutein and Zeaxanthin Differ with Age, Sex, and Ethnicity. J. Am. Diet. Assoc. 2010, 110, 1357-1362.

[0007] Gazzolo D, Picone S, Gaiero A, Bellettato M, Montrone G, Riccobene F, Lista G, Pellegrini G. Early Pediatric Benefit of Lutein for Maturing Eyes and Brain-An Overview. Nutrients. 2021 Sep 17;13(9):3239. doi: 10.3390 / nu13093239. PMID: 34579116; PMCID: PMC8468336.

[0007] Bone RA, Landrum JT, Friedes LM, Gomez CM, Kilburn MD, Menendez E, Vidal I, Wang W. Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res. 1997 Feb;64(2):211-8. doi: 10.1006 / exer.1996.0210. PMID: 9176055.

[0014] Wang H, Zhang C, Lu D, Shu X, Zhu L, Qi R, So KF, Lu D, Xu Y. Oligomeric proanthocyanidin protects retinal ganglion cells against oxidative stress-induced apoptosis. Neural Regen Res. 2013 Sep 5;8(25):2317-26. doi: 10.3969 / j.issn.1673-5374.2013.25.002. PMID: 25206541; PMCID: PMC4146041.

[0016] Matsumoto H, Kamm KE, Stull JT, Azuma H. Delphinidin-3-rutinoside relaxes the bovine ciliary smooth muscle through activation of ETB receptor and NO / cGMP pathway. Exp Eye Res. 2005 Mar;80(3):313-22. doi: 10.1016 / j.exer.2004.10.002. PMID: 15721614.

[0017] Nakaishi H, Matsumoto H, Tominaga S, Hirayama M. Effects of black current anthocyanoside intake on dark adaptation and VDT work-induced transient refractive alteration in healthy humans. Altern Med Rev. 2000 Dec;5(6):553-62. Erratum in: Altern Med Rev 2001 Feb;6(1):60. PMID: 11134978.

[0017] Lourenço R, Camilo ME. Taurine: a conditionally essential amino acid in humans? An overview in health and disease. Nutr Hosp. 2002 Nov-Dec;17(6):262-70. PMID: 12514918. Duan H, Song W, Guo J, Yan W. Taurine: A Source and Application for the Relief of Visual Fatigue. Nutrients. 2023 Apr 12;15(8):1843. doi: 10.3390 / nu15081843. PMID: 37111062; PMCID: PMC10142897.

[0018] Li LH, Lee JC, Leung HH, Lam WC, Fu Z, Lo ACY. Lutein Supplementation for Eye Diseases. Nutrients. 2020 Jun 9;12(6):1721. doi: 10.3390 / nu12061721. PMID: 32526861; PMCID: PMC7352796.

[0019] Rao S, Li T, Li X, Hou L, Sun W. Vitamin A and Its Related Diseases. Food Sci Nutr. 2025 Jul 15;13(7):e70630. doi: 10.1002 / fsn3.70630. PMID: 40672537; PMCID: PMC12263517.

[0020] Brigelius-Flohé R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999 Jul;13(10):1145-55. PMID: 10385606.

[0021] QUOTES INCLUDED IN THE DESCRIPTION

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

[0000] US 11173133B2 [0008, 0025] US 7282225B1 [0009, 0025] EP 2138055B1 [0010, 0025] US 20070166354A1 [0011, 0025] Cited non-patent literature

[0000] Giampietri M, Lorenzoni F, Moscuzza F, Boldrini A, Ghirri P. Lutein and Neurodevelopment in Preterm Infants. Front Neurosci. 2016 Sep 7;10:411. doi: 10.3389 / fnins.2016.00411. PMID: 27656124; PMCID: PMC5013125

[0026] Johnson EJ. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr Rev. 2014 Sep;72(9):605-12. doi: 10.1111 / nure.12133. Epub 2014 Aug 8. PMID: 25109868

[0027] EUROSTAT. Do You Eat Fruit and Vegetables Daily? Available online

[0028] https: / / ec.europa.eu / eurostat / web / products-eurostat-news / - / DDN-20190401-1

[0007] Johnson, E.J.; Maras, J.E.; Rasmussen, H.M.; Tucker, K.L. Intake of Lutein and Zeaxanthin Differ with Age, Sex, and Ethnicity. J. Am. Diet. Assoc. 2010, 110, 1357-1362

[0028] Gazzolo D, Picone S, Gaiero A, Bellettato M, Montrone G, Riccobene F, Lista G, Pellegrini G. Early Pediatric Benefits of Lutein for Maturing Eyes and Brain-An Overview. Nutrients. 2021 Sep 17;13(9):3239. doi: 10.3390 / nu13093239. PMID: 34579116; PMCID: PMC8468336

[0028] Wang H, Zhang C, Lu D, Shu X, Zhu L, Qi R, So KF, Lu D, Xu Y. Oligomeric proanthocyanidin protects retinal ganglion cells against oxidative stress-induced apoptosis. Neural Regen Res. 2013 Sep 5;8(25):2317-26. doi: 10.3969 / j.issn.1673–5374.2013.25.002. PMID: 25206541; PMCID: PMC4146041

[0028] Matsumoto H, Kamm KE, Stull JT, Azuma H. ​​Delphinidin-3-rutinoside relaxes bovine ciliary smooth muscle through activation of ETB receptor and NO / cGMP pathway. Exp Eye Res. 2005 Mar;80(3):313-22. doi: 10.1016 / j.exer.2004.10.002. PMID: 15721614

[0028] Nakaishi H, Matsumoto H, Tominaga S, Hirayama M. Effects of black current anthocyanoside intake on dark adaptation and VDT work-induced transient refractive alteration in healthy humans. Altern Med Rev. 2000 Dec;5(6):553-62. Erratum in: Altern Med Rev 2001 Feb;6(1):60. PMID: 11134978

[0028] Lourenço R, Camilo ME. Taurine: a conditionally essential amino acid in humans? An overview in health and disease. Nutr Hosp. 2002 Nov-Dec;17(6):262-70. PMID: 12514918

[0028] Duan H, Song W, Guo J, Yan W. Taurine: A Source and Application for the Relief of Visual Fatigue. Nutrients. 2023 Apr 12;15(8):1843. doi: 10.3390 / nu15081843. PMID: 37111062; PMCID: PMC10142897

[0028] Li LH, Lee JC, Leung HH, Lam WC, Fu Z, Lo ACY. Lutein Supplementation for Eye Diseases. Nutrients. 2020 Jun 9;12(6):1721. doi: 10.3390 / nu12061721. PMID: 32526861; PMCID: PMC7352796

[0028] Rao S, Li T, Li X, Hou L, Sun W. Vitamin A and Its Related Diseases. Food Sci Nutr. 2025 Jul 15;13(7):e70630. doi: 10.1002 / fsn3.70630. PMID: 40672537; PMCID: PMC12263517.

[0020] Brigelius-Flohé R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999 Jul;13(10):1145-55. PMID: 10385606

[0028]

Claims

[1] A micronutrient composition for infants and children from 6 months of age, characterized by , that it is a liquid oral formulation containing the following main active ingredients: microencapsulated lutein, microencapsulated zeaxanthin, proanthocyanidins, anthocyanins, taurine, zinc, vitamin A and vitamin E, the composition being intended to support healthy retinal development in infants, to relieve visual fatigue and to build an antioxidant defense system in the eye. [2] The composition according to claim 1, characterized by , that, based on a daily dose, it includes the following: 1 mg to 20 mg lutein, 0.2 mg to 4 mg zeaxanthin, 1 mg to 100 mg proanthocyanidins, 1 mg to 200 mg anthocyanins, 10 mg to 300 mg taurine, 0.5 mg to 7 mg zinc, 1 µg to 430 µg vitamin A and 1 mg to 9 mg vitamin E. [3] The composition according to claim 1 or 2, characterized by, that, based on a daily dose, it preferably comprises the following: 6 mg lutein, 1.2 mg zeaxanthin, 14.75 mg proanthocyanidins, 2 mg anthocyanins, 15 mg taurine, 1 mg zinc, 150 µg vitamin A, and 4 mg vitamin E. [4] Composition according to any one of claims 1 to 3, characterized by that the zeaxanthin includes its stereoisomer racemic zeaxanthin and that its content is more than 50% of the total zeaxanthin, preferably ≥ 1.02 mg / day. [5] Composition according to any one of claims 1 to 4, characterized by that lutein and zeaxanthin are extracted from natural marigold (Tagetes erecta) and encapsulated using microencapsulation to increase their water solubility and stability. [6] Composition according to any one of claims 1 to 5, characterized bythat the proanthocyanidins are obtained from grape seed extract (Vitis vinifera) and have a purity of at least 95% (based on proanthocyanidins). The anthocyanin source can be one or more commercially available plant anthocyanin extracts, such as blackcurrant (Ribes nigrum L.), bilberry (Vaccinium myrtillus), maqui berry (Aristotelia chilensis), bilberry (Vaccinium uliginosum L.), and Aronia melanocarpa, with an anthocyanin content of at least 25% in the extract. [7] The composition according to any one of claims 1 to 6, characterized by that the zinc is derived from an organic zinc salt, preferably zinc glycinate, zinc gluconate or zinc citrate. [8] The composition according to any one of claims 1 to 7, characterized by that the dosage form of the composition is selected from an oral liquid, a gel, soft capsules, gummy bears or powder, preferably an individually packaged liquid dosage form. [9] The composition according to any one of claims 1 to 8, characterized by that it contains no artificial colors, artificial fragrances and preservatives, and does not contain common allergens that trigger allergies.