WO2005110114A1 - Liquid nutritional supplement and method for preparing same - Google Patents

Liquid nutritional supplement and method for preparing same Download PDF

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Publication number
WO2005110114A1
WO2005110114A1 PCT/FR2005/050296 FR2005050296W WO2005110114A1 WO 2005110114 A1 WO2005110114 A1 WO 2005110114A1 FR 2005050296 W FR2005050296 W FR 2005050296W WO 2005110114 A1 WO2005110114 A1 WO 2005110114A1
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WO
WIPO (PCT)
Prior art keywords
nutritional supplement
composition
vitamin
supplement according
copper
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PCT/FR2005/050296
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French (fr)
Inventor
Olivier Roche
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Olivier Roche
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Publication date
Application filed by Olivier Roche filed Critical Olivier Roche
Priority to EP05759824A priority Critical patent/EP1753305A1/en
Publication of WO2005110114A1 publication Critical patent/WO2005110114A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A23P10/35—Encapsulation of particles, e.g. foodstuff additives with oils, lipids, monoglycerides or diglycerides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/34—Copper; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to the field of nutritional supplements useful in geriatrics, ophthalmology and which are in particular capable of fighting against ocular aging and retinal degeneration.
  • AMD 182,000 and 300,000 blind or partially sighted people following an AMD.
  • AMD is currently the leading cause of blindness in the Western world. Between 20 and 25 million people worldwide are affected. A figure that should triple in the next 30-40 years.
  • medical research directs scientists towards a role of food in the protection against this disease.
  • the French average age is currently evolving towards an aging population. This trend, which started a few years ago, is not corrected by the birth rate.
  • the demographic indicators highlight a growing and exponential proportion of subjects over the age of 45 for the years to come. This segment of the population has an above-average purchasing power and an increased demand for medical care with advancing age.
  • AMD age-related macular degeneration
  • the disease can appear in several clinical forms, some of which can benefit from laser or surgical techniques, but more often than not, the disease is beyond any therapeutic resource (advanced atrophic or neovascular form).
  • the results of these treatments most often consist of stabilization of the disease which has definitively settled; they sometimes irreparably impair the patient's visual capacity.
  • Pigmentary retinopathies are a set of degenerative diseases of the retina that lead to blindness. There is no preventive or curative treatment.
  • Zinc In the AREDS study, several cocktails were tested and also Zinc alone, which brings a reduction in the risk but by 25% less of the risk of worsening of the disease in people with treated, compared to untreated, and 13% less risk of visual impairment in people treated, compared to those not treated.
  • Lutein / Zeaxanthin Retinal pigments used in the physiological constitution of retinal cells. Blood and tissue levels lowered in people with AMD. Only possible intake, food (not synthesized by the body)
  • the nutritional supplements available to date are in solid forms such as capsules, tablets or the like.
  • European standards are different from those of the USA, more stringent in Europe on food supplements.
  • the problem lies in the fact that the dosage form of the product must give the consumer the possibility of absorbing only 100% of the recommended daily allowance (RDA): it is the legislation on the food supplement and not that of the drug.
  • RDA recommended daily allowance
  • the consumer is free to consume more if he wishes or if his doctor has prescribed it.
  • the most limiting factor for ease of intake is vitamin E, the quantity to be brought in compared to the AREDS study (reference) is the highest compared to the RDA (28 to 40 times depending on the form of vitamin E).
  • the subject of the present invention is also a liquid nutritional supplement characterized in that it consists of a composition comprising a combination of Cu (copper) and Zn
  • the enteral administration envisaged for this nutritional supplement includes liquid forms such as liquid compositions consumed orally (drinks, syrups) but also by gastric tube ( via tubes: jejunostomy, gastrostomy, nasoduodenal route).
  • the solution of the present invention providing for the first time in particular in the form of drinkable liquid said nutritional supplement, makes it possible to follow the recommendations of the AREDS study while eliminating the discomfort inevitably caused by a daily intake by patients of a large number of tablets (10 per day) or capsules (or capsules).
  • the present invention also relates to a method for preparing a liquid nutritional supplement comprising the steps consisting in (i) preparing a combination of Cu (copper) and Zn (zinc) in the form of lipodispersible microcapsules and (ii) dispersing the preparation ai nsi obtained in a mixture of vitamin E and vitamin C.
  • the present invention has finally been used for the composition according to the invention in the manufacture of a preparation for ru enteral administration in geriatrics, ophthalmology, especially for the treatment of DM LA, reti nopathies and ocular aging.
  • the present invention may now be described in detail and with the aid of exemplary embodiments which are given purely by way of non-limiting illustration.
  • Example 1 Drinkable oily form of the composition in accordance with the invention comprising Cu + Zn microencapsules + Vit E + Vit C.
  • Preparation of copper oxide microcapsules and d 'zinc oxide Particles of copper oxide powder are made to fluidize in a fluidized bed. The movement of the particles is adapted in front of the nozzles of a spraying device by which the encapsulating fat is sprayed in the liquid state in the fluidization tube. The whole is cooled with the aid of freezing the fat.
  • the fat consists of palm oil fractions with a melting point of 45 ° C to 65 ° C.
  • the micro-stirring is carried out so as to deposit 5 to 20%, preferably 1 0 to 1 5%, of fatty matter around the particles.
  • the microcapsules have an average diameter of the order of 1 00 to 500 microns, preferably 250 microns.
  • the "fines" which constitute the material not or not fully robed.
  • these can be removed by filtration, by choosing a sieve cutoff threshold of the order of 1,00 microns. This embodiment is particularly advantageous because it greatly reduces the pro-oxidant effect of copper.
  • Another variant of this technique consists in carrying out a second granulation / taping run in encapsulation tu nnel for carrying out a double coating.
  • the temperature of the fat must be lower than the melting point of the first coating fat in order to preserve the integrity of the microcapsules.
  • Zinc oxide microcapsules are prepared in an identical manner. Such microcapsules are in particular available from the company POLARIS. Copper can also be incorporated in a form different from copper oxide and chosen from the group consisting of carbonate, citrate, gluconate, copper sulphate.
  • Vitamin preparation is made liposoluble. Vit C esterifies a relatively long chain fatty acid such as pal mitic acid: Vit C is used here in the form of ascorbyl pal mitate, commonly available commercially.
  • the vitamin E used is advantageously in the form of D-alpha-tocopherol acetate because used in high doses the non-esterified form then has a prooxidative effect.
  • Vitamin E is in particular available from the company POLARIS under the trade name D-alpha-Tocopherol acetate.
  • a natural antioxidant can be added such that a mixture containing at least 70% of tocopherols (rich in delta and gamma form).
  • a chelating agent is added to the composition in an oily state such as soy lecithin (not GMO-I P ) for example.
  • Such a product is available in particular from the company STERN under the name Sterncithine.
  • the desired viscosity of the composition according to the invention is from 75 to 80 Mpa.s.
  • a flavor can be added such as strawberry, caramel chocolate, strawberry chocolate, tutti frutti, banana or lemon.
  • Such aromas are available from the company G IVAU DAN.
  • the operations of mixing the various constituent elements of the composition are preferably carried out in avoiding any heating and advantageously under vacuum or under an inert atmosphere (nitrogen, argon).
  • a typical composition comprises by weight per cent of the total composition: Zn 1.06% Cu 0.03% Vit C 23.93% Vit E 3.07%
  • the optional additives or excipients are typically present at the rate of: Antioxidant 0.29% Aroma 1.07% MCT qs 1 00%
  • Example 2 Oily form of the composition according to the invention comprising other active agents, in particular omega 3 and Vit. A, lutei ne, Zéaxanthi ne, and Sonuliu m.
  • At least one polyunsatu fatty acid of the “Omega 3” type thus docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alphalinolenic acid (ALA) alone or as a mixture.
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • ALA alphalinolenic acid
  • a mixture preferably containing 20-93% of DHA is added, the remainder being essentially formed of EPA.
  • Such a product is available from POLARIS under the trade name EPAX 1 050 TG (1 0% EPA, 50% DHA).
  • Vitami ne A preferably to be added in the form of its precursor beta-carotene available in particular from the company ROCHE under the trade name Beta-carotene 30% FS or in the form of Vitaminate.
  • Lutein is also added: it is in the form of a powder made liposoluble in a mixture of medium to medium triglycerides and short chains (MCT) prior to its addition.
  • MCT medium to medium triglycerides and short chains
  • Such a product is in particular available from the company SOPRAL under the trade name Lutei n powder OS 24.
  • Zeaxanthi ne before being added to the mixture it is preferably dissolved in an alcohol, for example ethanol.
  • Such a product is available from the company PIVEG under the trade name Zeaxanthin oil 20%.
  • Selenium trace element added in the form of particles of selected yeast powder suspended in oil. Such a product is available from QU IM DIS
  • Antioxidants such as a mixture of tocopherols, such as the product which is available from POLARIS under the trade name Oxynat 70 IP, or Coenzyme Q1 0, or an extract de romari n, pre-emulsion born so as to be dispersible in oil.
  • Agent chelateu r lecithi ne already mentioned above.
  • Sugars to be added in the form of glucose syrup, fructose, forming a dispersion or sweeteners, in particular aspartame
  • Example of an oily composition in accordance with the invention Vit. C (ascorbyl palmitate) 23.93% Omega 3 14.56% Vit. E (D-alpha-tocopherol) 3.07% Zinc oxide (microencapsulated) 1.06% Vit.
  • Vitamin C (beta carotene) 0.47% Lutein 0.31% Copper oxide (microencapsulated) 0.03% Zeaxanthi ne 0.01% Selenium 0.01% MCT 55, 1 9% Strawberry flavor 1.07% Antioxidant 0.29%
  • the percentages by weight percent of Vitamin C of the constituents of a typical composition according to the invention are as follows: Copper 0.11% Zinc 4.42 % Vit E 12.84% Vit A 1.98% and those of the optional constituents, when present, are as follows: Omega 3 60.83% Lutein 1.31% Zeaxanthin 0.03% Selenium 0.02% Antioxidant 1.21%
  • Example 3 Form of drinkable aqueous emulsion type of the composition in accordance with the invention
  • the emulsion is prepared as follows: To an aqueous solution comprising all the water-soluble compounds is added an emulsifier such as lecithin and poured under vigorous stirring - by example, using a device with 2 rotors rotating in opposite directions to have a strong shear - the oily composition of example 1 or 2 with the exception of the microcapsules which are then added and mixed with a gentle stirring - for example with a paddle stirrer. Size of the oily particles from 3 to 10 microns, preferably from 4 to 6 microns. Beyond 10 microns, there is a risk of coalescence.
  • an emulsifier such as lecithin
  • poured under vigorous stirring - by example, using a device with 2 rotors rotating in opposite directions to have a strong shear - the oily composition of example 1 or 2 with the exception of the microcapsules which are then added and mixed with
  • a typical emulsion according to the invention comprises: Aqueous phase 30-40% Emulsifier 3-7% Oily phase qs 100% In the aqueous phase, it is advantageous to add a gum of the guar, xanthan or related gum type.
  • the addition of the oily phase is carried out with vigorous stirring using a homogenizer such as Ultratu rax or equivalent.
  • the microcapsules are only added, with slow stirring, once the emulsion has been produced.
  • Example 4 Form of drinkable gel type of the composition in accordance with the invention 4.1.
  • Example of a preparation of a gel type emulsion 1 / Disperse sodium alginate (1%) in water with vigorous stirring.
  • a gel is obtained.
  • Another example It is possible to also use carrageenans (0.5%) in solution in water and in the presence of sodium citrate (0.25%). Steps to prepare a gel-type emulsion: 1 / Dry mix the carrageenans and soda citrate m. 2 / Disperse the mixture obtained in 1 / in water with vigorous stirring.
  • a typical gel according to the invention comprises: Water 25-50% Algi nate of sodiu m 1% Sulfate of calciu m 1% Emulsion 48-73% Instead of the emulsion one can consider incorporating the oil , as previously mentioned.
  • Example 5 Dry preparation for nutritional supplement drinkable liquid extemporaneous such as all forms of powder (s), granulate (s), water-soluble tablets constitutable extemporaneous in a little water or a liquid.
  • the basic composition is for example formed from: - Powder of microcapsules of zinc oxide and of copper - Vit. E which is microencapsulated by putting in the form of powder sprayed by nebulization above a support. It is preferably prepared by adsorption on a support of the amorphous silica type on which the fatty encapsulation material is then deposited.
  • - Vit C can be added as it is or in microencapsulated form or else in the form of ascorbyle palmitate.
  • - Omega 3 are in microencapsule form and are preferably obtained from an emulsion comprising omega 3 in water, one or more emulsifiers. This emulsion is then dried and then encapsulated. To obtain a water-soluble powder, an atomization process is applied on a specific preparation or oil-based emulsion consisting of at least 40% dry form of caseinate. This initial oily mixture may contain in the proportions already described for the oily liquid form of omega 3, vitamins A and E and lutein. Assets water-soluble type vitamin C, lycopene, selenium yeast or trace elements such as zinc and copper (respectively in the form of oxide or gluconate) are then added to this powder in the proportions already defined.
  • the atomization consists of the injection under pressure by a spray nozzle, into an enclosure heated by air drawn at 80 ° C. at the heart, of the mixture described above.
  • the flavoring of the mixture can be obtained either by adding a flavoring powder, or by incorporating an aromatic oil into the initial oily mixture before spraying.
  • Such a product is available from the POLARIS company under the trade name omegacaps® DHA C.

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Abstract

A liquid nutritional supplement, characterised in that it consists of a composition comprising a Cu (copper) and Zn (zinc) combination in the form of fat-dispersible microcapsules in a vitamin E and C mixture. The present invention also relates to a method for preparing a liquid nutritional supplement including (i) preparing a Cu (copper) and Zn (zinc) combination in the form of fat-dispersible microcapsules and (ii) dispersing the resulting preparation in a vitamin E and C mixture. The nutritional supplement according to the invention, administered by enteral delivery, is useful in geriatrics and ophthalmology, in particular in the treatment of age-related maculopathy, of retinitis pigmentosa and eye ageing.

Description

« Complément nutritionnel liquide et procédé de préparation de ce complément » "Liquid nutritional supplement and process for preparing this supplement"
DOMAINE DE L'INVENTIONFIELD OF THE INVENTION
La présente invention a trait au domaine des compléments nutritionnels utiles en gériatrie, ophtalmologie et qui sont notamment aptes à lutter contre le vieillissement oculaire et la dégénérescence rétinienne.The present invention relates to the field of nutritional supplements useful in geriatrics, ophthalmology and which are in particular capable of fighting against ocular aging and retinal degeneration.
ART ANTERIEURPRIOR ART
Depuis plusieurs années, l'absence de traitement contre la DMLA (dégénérescence maculaire liée à l'âge), une maladie fréquente mais ignorée du grand public est un problème quotidien des consultations ophtalmologiques. Un rapport de l'ONU estime à 20-25 millions les individus présentant une DMLA. L'OMS estime à 8 millions la population de malvoyants dans le monde. Le nombre de personnes âgées de plus de 60 ans devrait passer de 606 millions en 2000 à 2 milliards en 2050. On s'attend à ce que la population au-dessus de 80 ans passe de 69 millions en 2000 à 379 millions en 2050. Les personnes âgées de plus de 60 ans représentent environ 20% de la population dans la plupart des régions développées du globe et représenterons environ 33% en 2050. Au Royaume Uni on estime qu'il y aura environ 16 millions de personnes au-dessus de 60 ans en 2040. Dans une étude récente, Fletcher et al. estiment entreFor several years, the lack of treatment for AMD (age-related macular degeneration), a frequent disease but ignored by the general public, has been a daily problem in ophthalmological consultations. A UN report estimates that 20-25 million people have AMD. WHO estimates that 8 million people are visually impaired worldwide. The number of people over the age of 60 is expected to increase from 606 million in 2000 to 2 billion in 2050. The population over the age of 80 is expected to increase from 69 million in 2000 to 379 million in 2050. People over the age of 60 make up around 20% of the population in most developed regions of the globe and will account for around 33% in 2050. In the UK it is estimated that there will be around 16 million people above 60 years in 2040. In a recent study, Fletcher et al. estimate between
182000 et 300000 les personnes aveugles ou partiellement voyantes suite à une DMLA. La DMLA est à l'heure actuelle la principale cause de cécité dans le monde occidental. Entre 20 et 25 millions de person nes dans le monde en sont affectées. U n chiffre qui devrait tripler dans les prochaines 30-40 an nées. Dans le même temps, la recherche médicale oriente les scientifiques vers un rôle des aliments dans la protection contre cette maladie. L'âge moyen français évolue actuellement vers u n vieillissement de la population. Cette tendance amorcée depuis quelques an nées n'est pas corrigée par la natalité. Les indicateu rs démographiques mettent en évidence u ne proportion grandissante et exponentielle des sujets âgés de plus de 45 ans pou r les années à veni r. Cette tranche de la population a un pouvoi r d'achat supérieu r à la moyenne et une demande de soins médicaux accrue à mesure de l'avance de l'âge. Dans les pays développés, la première cause de cécité du sujet âgé de plus de 50 ans est la dégénérescence maculai re liée à l'âge (DMLA) ; la cécité ne signifie pas une absence totale de vision mais une acuité visuelle inférieu re à 1 /20e. Il existe deux formes cli niques distinctes, la forme atrophique (sèche) et la forme néovasculai re (humide). U n dépistage précoce de la DMLA est difficile mais des marqueurs cliniques (éléments vus à la consultation médicale) appelés drusens sont souvent retrouvés ; ils correspondent à u ne accumulation de déchets sous rétiniens. La DMLA, en France, menace envi ron 2 millions de personne attei ntes de signes précu rseu rs précoces de maculopathie liée à l'âge associée aux drusen, les formes sévères concernant plus de 200 000 person nes (prévalence de la DMLA avérée). Il n'existe aucun traitement préventif pouvant stopper l'évolution de la maladie mais seulement des traitements cu ratifs de formes évoluées entraînant des séquelles. Récemment, des études recherchant les facteurs de risques de cette maladie ont permis de retrouver notamment l'âge, les antécédents familiaux ou personnels mais aussi l'intervention de la cataracte et les iris clairs (yeux bleus). Plus l'âge est avancé et plus la fréquence de survenue de la maladie (incidence) augmente. Le nombre de personnes âgées et l'espérance de vie augmentent. La DMLA est donc une maladie particulièrement fréquente qui atteint la rétine au niveau de sa zone la plus fragile, la macula. Cette petite zone permet la lecture, la reconnaissance des visages et les détails fins de notre vision assurant 10/10ème. Le mécanisme causal est inconnu mais des phénomènes d'oxydation sont retrouvés dans les éléments favorisant la survenue de l'atteinte tissulaire. La maladie peut se présenter sous plusieurs formes cliniques dont certaines peuvent bénéficier de techniques laser ou chirurgicale mais le plus souvent, la maladie est au delà de toute ressource thérapeutique (forme atrophique ou néovasculaire évoluée). Les résultats de ces traitements consistent le plus souvent en une stabilisation de la maladie définitivement installée ; ils altèrent parfois irrémédiablement la capacité visuelle du patient. Les rétinopathies pigmentaires sont un ensemble de maladies dégénératives de la rétine aboutissant à la cécité. Il n'existe pas de traitement préventif ni curatif.182,000 and 300,000 blind or partially sighted people following an AMD. AMD is currently the leading cause of blindness in the Western world. Between 20 and 25 million people worldwide are affected. A figure that should triple in the next 30-40 years. At the same time, medical research directs scientists towards a role of food in the protection against this disease. The French average age is currently evolving towards an aging population. This trend, which started a few years ago, is not corrected by the birth rate. The demographic indicators highlight a growing and exponential proportion of subjects over the age of 45 for the years to come. This segment of the population has an above-average purchasing power and an increased demand for medical care with advancing age. In developed countries, the primary cause of blindness in people over the age of 50 is age-related macular degeneration (AMD); blindness does not mean a total lack of vision but a visual acuity less than 1 / 20th. There are two distinct clinical forms, the atrophic form (dry) and the neovascular form (wet). Early detection of AMD is difficult, but clinical markers (elements seen at the medical consultation) called drusens are often found; they correspond to an accumulation of subretinal waste. AMD in France threatens approximately 2 million people with early warning signs of age-related maculopathy associated with drusen, severe forms affecting more than 200,000 people (prevalence of AMD proven). There is no preventive treatment that can stop the progression of the disease, but only remedial treatments of advanced forms resulting in sequelae. Recently, studies looking for risk factors for this disease have made it possible to find in particular age, family or personal history but also the intervention of cataracts and light irises (blue eyes). The older the age, the more the frequency of onset of the disease (incidence) increases. The number of elderly people and life expectancy are increasing. AMD is therefore a particularly frequent disease which affects the retina in its most fragile area, the macula. This small area allows the reading, the recognition of faces and the fine details of our vision ensuring 10 / 10th. The causal mechanism is unknown but oxidation phenomena are found in the elements favoring the occurrence of tissue damage. The disease can appear in several clinical forms, some of which can benefit from laser or surgical techniques, but more often than not, the disease is beyond any therapeutic resource (advanced atrophic or neovascular form). The results of these treatments most often consist of stabilization of the disease which has definitively settled; they sometimes irreparably impair the patient's visual capacity. Pigmentary retinopathies are a set of degenerative diseases of the retina that lead to blindness. There is no preventive or curative treatment.
PROBLEMES RESOLUS DANS L'ART ANTERIEUR Les traitements du vieillissement oculaire et de la dégénérescence rétinienne proposés aujourd'hui comportent la micronutrition par les compléments alimentaires à visée oculaire. Il s'agit de développer des cocktails vitaminiques dont les compositions ont été testées par des études scientifiques publiées dans des jou rnaux internationaux à comité de lectu re. Préventivement, des produits aidant les défenses naturelles enzymatiques de la rétine contre les toxiques ont été donnés aux patients dans le cadre d'études scientifiques statistiquement validées. Des cocktails de vitami nes, d'anti-oxydants et d'oligo- éléments sont fréquem ment prescrits notamment aux Etats-Unis. Ainsi les résultats de l'étude AREDS (Age-related Disease Study) incluant 3640 patients âgés de 55 à 80 ans et suivis pendant plus de 6 ans vien nent d'être publiés. Les résultats démontrent u ne moindre progression statistiquement significative de la maladie vers u ne forme sévère (atrophie ou néovascularisation) après prise de ces suppléments alimentai res : 28% de moi ns du risque d'aggravation de la maladie chez les person nes atteintes traitées, par rapport aux non traitées, 21 % de moins du risque de baisse visuelle chez les personnes traitées, par rapport aux non traitées. Les patients déjà attei nts d'u ne forme sévère su r u n œil ou de lésions prédisposantes étaient ceux bénéficiant du meilleu r effet protecteu r. La micronutrition est aujou rd'hui le seul traitement préventif ayant fait ses preuves dans la prise en charge de la DM LA. Après la démonstration d'un rôle protecteu r marqué d'u n taux sérique élevé de vitamine C ou de vitami ne E et d'une réduction du risque de DMLA chez les patients ayant une alimentation riche en vitamine A, u ne étude plus large a été proposée. Les résultats ont démontré l'efficacité d'u n cocktail vitaminique A,C,E et oligoéléments zinc et cuivre. Une contre indication est imposée à l'égard des fumeurs pour qui la vitamine A à forte dose majore le risque de cancer des bronches. INTERET DES DIFFERENTS CONSTITUANTS DES COMPLEMENTS NUTRITIONNELSPROBLEMS SOLVED IN THE PRIOR ART The treatments for ocular aging and retinal degeneration proposed today include micronutrition by dietary supplements for ocular purposes. It is about developing vitamin cocktails whose compositions have been tested by scientific studies published in international journals with reading committee. As a preventive measure, products helping the natural enzymatic defenses of the retina against toxins have been given to patients within the framework of statistically validated scientific studies. Vitamins, antioxidants and trace elements cocktails are frequently prescribed, especially in the United States. The results of the Age-related Disease Study (AREDS), including 3640 patients aged 55 to 80 and followed for more than 6 years, have just been published. The results demonstrate that there is no statistically significant progression from the disease to a severe form (atrophy or neovascularization) after taking these food supplements: 28% of me at risk of worsening of the disease in people with affected treatment, compared to untreated, 21% less risk of visual impairment in people treated, compared to untreated. The patients already suffering from a severe form of the eye or predisposing lesions were those benefiting from the best protective effect. Micronutrition is today the only proven preventive treatment in the management of DM LA. After demonstrating a marked protective role in a high serum level of vitamin C or vitamin E and a reduction in the risk of AMD in patients with a diet rich in vitamin A, a larger study has been proposed. The results demonstrated the effectiveness of a vitamin cocktail A, C, E and zinc and copper trace elements. A contraindication is imposed with regard to smokers for whom vitamin A in high doses increases the risk of bronchial cancer. INTEREST OF THE DIFFERENT CONSTITUENTS OF NUTRITIONAL SUPPLEMENTS
Zinc : Dans l'étude AREDS plusieurs cocktails ont été testés et également le Zinc seul qui apporte une diminution du risque mais de 25% de moins du risque d'aggravation de la maladie chez les personnes atteintes traitées, par rapport aux non traitées, et 13% de moins du risque de baisse visuelle chez les personnes traitées, par rapport aux non traitées.Zinc: In the AREDS study, several cocktails were tested and also Zinc alone, which brings a reduction in the risk but by 25% less of the risk of worsening of the disease in people with treated, compared to untreated, and 13% less risk of visual impairment in people treated, compared to those not treated.
Cuivre : Contre les effets délétères du Zinc avec les troubles hématologiques induits. Luthéine / Zéaxanthine : Pigments rétiniens entrant dans la constitution physiologique des cellules de la rétine. Taux sanguin et tissulaire abaissés chez les sujets atteints de DMLA. Seul apport possible, alimentaire (non synthétisé par l'organisme)Copper: Against the deleterious effects of Zinc with the induced hematological disorders. Lutein / Zeaxanthin: Retinal pigments used in the physiological constitution of retinal cells. Blood and tissue levels lowered in people with AMD. Only possible intake, food (not synthesized by the body)
Oméga 3 : Action rétinienne (constituant lipidique des membranes cellulaires et structure des photorécepteurs), action vasculaire, action film lacrymal. Il est également possible de démontrer une amélioration de la composante lipidique du film lacrymal utile dans la blépharite et l'œil sec. Aux Etats-Unis il vient d'être publiée une étude démontrant l'efficacité de l'utilisation des corps gras de ce type pour ces pathologies. INCONVENIENTS DES COMPLEMENTS NUTRITIONNELS CONNUSOmega 3: Retinal action (lipid constituent of cell membranes and structure of photoreceptors), vascular action, tear film action. It is also possible to demonstrate an improvement in the lipid component of the lacrimal film useful in blepharitis and dry eye. In the United States, a study has just been published demonstrating the effectiveness of the use of fatty substances of this type for these pathologies. DISADVANTAGES OF KNOWN NUTRITIONAL SUPPLEMENTS
A la connaissance de l'inventeur, les compléments nutritionnels disponibles à ce jour se présentent sous des formes solides telles que gélules, comprimés ou apparentés. Il existe un problème de dose de vitamine par comprimé par rapport aux apports journaliers recommandés. En effet, les normes européennes sont différentes de celles des USA, plus strictes en Europe sur les compléments alimentaires. Le problème réside dans le fait que la galénique du produit doit laisser au consommateur la possibilité de n'absorber que 100% des apports journaliers recommandés (AJR) : c'est la législation sur le complément alimentaire et non celle du médicament. Le consommateur étant libre de consommer plus s'il le souhaite ou si son médecin le lui a prescrit. Le facteur le plus limitant pour la facilité de prise est la vitamine E dont la quantité à apporter par rapport à l'étude AREDS (référence) est la plus élevée par rapport aux AJR (28 à 40 fois selon la forme de vitamine E). En effet, les normes d'équivalence milligramme/unité internationale et les normes de fabrication pour la vitamine E ne sont pas les mêmes pour toutes les formes chimiques de vitamine E. Enfin, on peut diminuer la dose de vitamine E et (donc changer les proportions de l'étude) avec encore un grand nombre de capsules (6/jour) ou gélules (6/jour) pour « coller » à la législation mais avec une perte du respect de l'étude AREDS et d'effet lié à la vitamine E. Si on suit les recommandations de l'étude AREDS on a un volume important de matière notamment gros comprimés à ingérer avec risque de fausse route alimentaire chez des sujets à risque (personnes âgées), ce qui est l'inconvénient potentiellement dangereux des formes galéniques actuellement sur le marché. Il existe donc le besoin d'un complément nutritionnel qui ne présente pas d'inconvénient pour le consommateur tout en procurant surtout des actifs et peu d'excipients. SOLUTION DE L'INVENTIONTo the knowledge of the inventor, the nutritional supplements available to date are in solid forms such as capsules, tablets or the like. There is a problem of vitamin dose per tablet compared to the recommended daily allowance. Indeed, European standards are different from those of the USA, more stringent in Europe on food supplements. The problem lies in the fact that the dosage form of the product must give the consumer the possibility of absorbing only 100% of the recommended daily allowance (RDA): it is the legislation on the food supplement and not that of the drug. The consumer is free to consume more if he wishes or if his doctor has prescribed it. The most limiting factor for ease of intake is vitamin E, the quantity to be brought in compared to the AREDS study (reference) is the highest compared to the RDA (28 to 40 times depending on the form of vitamin E). In fact, the milligram / international unit equivalence standards and the manufacturing standards for vitamin E are not the same for all chemical forms of vitamin E. Finally, we can reduce the dose of vitamin E and (therefore change the proportions of the study) with a large number of capsules (6 / day) or capsules (6 / day) to "stick" to the legislation but with a loss of respect for the AREDS study and of effect linked to the Vitamin E. If we follow the recommendations of the AREDS study, we have a large volume of material, in particular large tablets to ingest with the risk of a false food route in subjects at risk (elderly), which is the potentially dangerous disadvantage of dosage forms currently on the market. There is therefore a need for a nutritional supplement which does not present any inconvenience for the consumer while above all providing active agents and few excipients. SOLUTION OF THE INVENTION
Ce besoin est satisfait par la présente invention qui procure un complément nutritionnel sous forme liquide. Aussi la présente invention a pour objet un complément nutritionnel liquide caractérisé en ce qu'il consiste en une composition comportant une association de Cu (cuivre) et de ZnThis need is satisfied by the present invention which provides a nutritional supplement in liquid form. The subject of the present invention is also a liquid nutritional supplement characterized in that it consists of a composition comprising a combination of Cu (copper) and Zn
(zinc) sous forme de microcapsules lipodispersibles dans un mélange de Vitamine E et de Vitamine C. L'administration entérale envisagée pour ce complément nutritionnel regroupe les formes liquides telles que les compositions liquides consommées oralement (boissons, sirops) mais aussi par sonde gastrique (via des tubes : jejunostomie, gastrostomie, voie naso-duodénale). La solution de la présente invention, procurant pour la première fois notamment sous forme de liquide buvable ledit complément nutritionnel, permet de suivre les recommandations de l'étude AREDS tout en supprimant la gêne inévitablement occasionnée par une prise au quotidien par les patients d'un grand nombre de comprimés (10 par jour) ou capsules (ou gélules). Outre sa facilité de consommation il simplifie la vie des sujets âgés prenant déjà de nombreux cachets chaque jour car le complément nutritionnel se présente sous une forme galénique aisée à absorber, à manipuler et notamment d'un volume facile à avaler. La présente invention a également pour objet un procédé de préparation d'un complément nutritionnel liquide comprenant les étapes consistant à (i) préparer une association de Cu (cuivre) et de Zn (zinc) sous forme de microcapsules lipodispersibles et (ii) disperser la préparation ai nsi obtenue dans un mélange de vitami ne E et vitamine C. La présente i nvention a enfi n pou r objet une utilisation de la composition conforme à l'invention dans la fabrication d'une préparation pou r u ne admi nistration entérale en gériatrie, ophtalmologie, notamment pou r le traitement de la DM LA, des réti nopathies et du vieillissement oculai re. La présente invention va mai ntenant être décrite de manière détaillée et à l'aide d'exemples de réalisation qui sont donnés à titre purement illustratif et non limitatif.(zinc) in the form of lipodispersible microcapsules in a mixture of Vitamin E and Vitamin C. The enteral administration envisaged for this nutritional supplement includes liquid forms such as liquid compositions consumed orally (drinks, syrups) but also by gastric tube ( via tubes: jejunostomy, gastrostomy, nasoduodenal route). The solution of the present invention, providing for the first time in particular in the form of drinkable liquid said nutritional supplement, makes it possible to follow the recommendations of the AREDS study while eliminating the discomfort inevitably caused by a daily intake by patients of a large number of tablets (10 per day) or capsules (or capsules). In addition to its ease of consumption it simplifies the life of elderly subjects already taking many pills each day because the nutritional supplement is in a dosage form easy to absorb, to handle and in particular of a volume easy to swallow. The present invention also relates to a method for preparing a liquid nutritional supplement comprising the steps consisting in (i) preparing a combination of Cu (copper) and Zn (zinc) in the form of lipodispersible microcapsules and (ii) dispersing the preparation ai nsi obtained in a mixture of vitamin E and vitamin C. The present invention has finally been used for the composition according to the invention in the manufacture of a preparation for ru enteral administration in geriatrics, ophthalmology, especially for the treatment of DM LA, reti nopathies and ocular aging. The present invention may now be described in detail and with the aid of exemplary embodiments which are given purely by way of non-limiting illustration.
DESCRI PTION DETAI LLEEDETAILED DESCRIPTION
Lors de ses recherches pou r mettre au poi nt de nouvelles formes galeniques, autres que solides, de complément nutritionnel à base de cuivre, zi nc, vitamine E et vitamine C, l'i nventeur a testé différentes formes liquides aqueuses, en sirop par exemple. Les i nconvénients de ces formes liquides aqueuses, empêchant défi nitivement leu r utilisation, proviennent des réactions d'oxydoréductions du cuivre qui dégradent les vitami nes, donnant par ailleu rs u n goût impropre à la consommation . EXEMPLESDuring his research to develop new galenic forms, other than solid, of nutritional supplement based on copper, zinc, vitamin E and vitamin C, the inventor tested various aqueous liquid forms, in syrup by example. The disadvantages of these aqueous liquid forms, which definitively prevent their use, come from redox reactions of copper which degrade the vitamins, thereby giving a taste unfit for consumption. EXAMPLES
Exemples de réalisation de compositions pou r les compléments nutritionnels de l'invention Exemple 1 : Forme huileuse buvable de la composition conforme à l'invention comprenant Cu + Zn microencapsules + Vit E + Vit C. Préparation des microcapsules d'oxyde de cuivre et d'oxyde de zinc : Des particules de poudre d'oxyde de cuivre sont mises à fluidiser dans u n lit fluidisé. On adapte le mouvement des particules devant les buses d'un dispositif de pulvérisation par lesquelles est pulvérisée de la matière grasse d'encapsulation à l'état liquide dans le tu nnel de fluidisation. On refroidit à l'ai r l'ensemble pou r figer la matière grasse. La matière grasse consiste en des fractions d'huile de pal me dont le point de fusion est de 45 °C à 65 °C. Le microen robage est réalisé de sorte à déposer de 5 à 20%, de préférence 1 0 à 1 5%, de matière grasse autour des particules. Les microcapsules ont un diamètre moyen de l'ordre de 1 00 à 500 microns, de préférence 250 microns. Par ce procédé il peut se fai re que quelques particules d'oxyde ne soient pas complètement encpasulees au risque d'occasion ner u ne peroxydation du mélange huileux. Très souvent, ce sont les particules les plus petites, les "fines" qui constituent le matériel non ou non totalement en robé. De préférence celles-ci peuvent être éli minées par filtration , en choisissant un seuil de coupure au tamis de l'ordre de 1 00 microns. Ce mode de réalisation est particulièrement avantageux car il dimi nue grandement l'effet pro-oxydant du cuivre. U ne autre variante de cette tech nique, consiste à effectuer un deuxième passage granulation/en robage en tu nnel d'encapsulation pou r réaliser u n double enrobage. Lors de cette 2θmθ pulvérisation , la température de la matière grasse doit être inférieu re au point de fusion de la première matière grasse d'enrobage afi n de préserver l'i ntégrité des microcapsules. On prépare de manière identique des microcapsules d'oxyde de zinc. De telles microcapsules sont notamment disponibles auprès de la société POLARIS. Le cuivre peut également être incorporé sous u ne forme différente de l'oxyde de cuivre et choisie dans le groupe constitué par carbonate, citrate, gluconate, sulfate de cuivre. De même, comme autres sou rces de zi nc que l'oxyde de zi nc, on peut utiliser acétate, chloru re, citrate, gluconate, lactate, carbonate et sulfate de zinc. Préparation des vitamines : La vitami ne C est rendue liposoluble. La Vit C estérifie un acide gras à relativement longue chaîne tel que l'acide pal mitique : la Vit C est utilisée ici sous forme de pal mitate d'ascorbyle, couramment disponible dans le commerce. La vitamine E utilisée est avantageusement sous forme de D-alpha-tocophérol acétate car utilisée à forte dose la forme non estérifiée a alors u n effet prooxydant. Etant très visqueuse elle est diluée dans une huile, de préférence u n mélange dit « MCT » de triglycérides à moyenne et courte chaîne en C8-Cι0 ; la vitamine E est notamment disponible auprès de la société POLARIS sous la dénomination com merciale D-alpha-Tocophérol acétate . U n anti-oxydant natu rel peut être ajouté tel qu'u n mélange contenant au moins 70% de tocophérols (riche en forme delta et gamma). Un tel produit est disponible auprès de la société POLARIS sous la dénomination commerciale Oxynat 70 I P. De préférence encore, on ajoute à la composition un agent chelateu r à l'état huileux tel que la lecithi ne de soja (non OGM-I P) par exemple. Un tel produit est disponible notamment auprès de la société STERN sous la dénomination Sterncithine. La viscosité sou haitée de la composition conforme à l'i nvention est de 75 à 80 Mpa.s. U n arôme peut être ajouté du type fraise, chocolat caramel , chocolat fraise, tutti frutti, banane ou citron . De tels arômes sont disponibles auprès de la société G IVAU DAN. Les opérations de mélange des différents éléments constitutifs de la composition sont réalisées de préférence en évitant tout échauffement et avantageusement sous vide ou sous atmosphère i nerte (azote, argon). U ne composition typique comprend en poids pou r cent de la composition totale : Zn 1 ,06% Cu 0,03% Vit C 23,93% Vit E 3,07% Les additifs ou excipients optionnels sont typiquement présents à raison de : Antioxydant 0,29 % Arôme 1 ,07% MCT qsp 1 00% Exemple 2 : Forme huileuse de la composition conforme à l'i nvention comprenant d'autres actifs, notamment oméga 3 et Vit. A, luthéi ne, Zéaxanthi ne, et Séléiu m. A la composition huileuse telle que décrite à l'exemple 1 on ajoute les autres actifs suivants : Au moins un acide gras polyi nsatu ré de type « Oméga 3 » : ainsi on ajoute l'acide docosahexaénoique (DHA), l'acide eicosapentaénoique (EPA), l'acide alphalinolénique (ALA) seul ou en mélange. Dans la présente invention on ajoute de préférence un mélange contenant 20-93% de DHA, le reste étant essentiellement formé d'EPA. Un tel produit est disponible auprès de la société POLARIS sous la dénomi nation com merciale EPAX 1 050 TG (1 0%EPA, 50%DHA). La Vitami ne A : à ajouter de préférence sous la forme de son précu rseu r beta-carotène disponible notamment auprès de la société ROCHE sous la dénomination commerciale Beta-carotene 30% FS ou sous forme de pal mitate de Vit. A. On ajoute également : Lutéine : elle se présente sous forme d'une poudre rendue liposoluble dans u n mélange de triglycérides à moyen nes et cou rtes chaînes (MCT) préalablement à son ajout. U n tel produit est notam ment disponible auprès de la société SOPRAL sous la dénomination commerciale Lutei n poudre OS 24. Zéaxanthi ne : avant d'être ajoutée au mélange elle est de préférence dissoute dans un alcool par exemple l'ethanol . Un tel produit est disponible auprès de la société PIVEG sous la dénomination commerciale Zeaxanthin oil 20%. Sélénium : oligo-élément ajouté sous forme de particules de poudre de levu re séléniée en suspension dans l'huile. U n tel produit est disponible auprès de la société QU I M DISExamples of making compositions for the nutritional supplements of the invention Example 1: Drinkable oily form of the composition in accordance with the invention comprising Cu + Zn microencapsules + Vit E + Vit C. Preparation of copper oxide microcapsules and d 'zinc oxide : Particles of copper oxide powder are made to fluidize in a fluidized bed. The movement of the particles is adapted in front of the nozzles of a spraying device by which the encapsulating fat is sprayed in the liquid state in the fluidization tube. The whole is cooled with the aid of freezing the fat. The fat consists of palm oil fractions with a melting point of 45 ° C to 65 ° C. The micro-stirring is carried out so as to deposit 5 to 20%, preferably 1 0 to 1 5%, of fatty matter around the particles. The microcapsules have an average diameter of the order of 1 00 to 500 microns, preferably 250 microns. By this process it may happen that some oxide particles are not completely encased at the risk of occasioning a peroxidation of the oily mixture. Very often, it is the smallest particles, the "fines" which constitute the material not or not fully robed. Preferably, these can be removed by filtration, by choosing a sieve cutoff threshold of the order of 1,00 microns. This embodiment is particularly advantageous because it greatly reduces the pro-oxidant effect of copper. Another variant of this technique consists in carrying out a second granulation / taping run in encapsulation tu nnel for carrying out a double coating. During this 2 θmθ spraying, the temperature of the fat must be lower than the melting point of the first coating fat in order to preserve the integrity of the microcapsules. Zinc oxide microcapsules are prepared in an identical manner. Such microcapsules are in particular available from the company POLARIS. Copper can also be incorporated in a form different from copper oxide and chosen from the group consisting of carbonate, citrate, gluconate, copper sulphate. Similarly, as other sources of zinc than zinc oxide, acetate, chloride, citrate, gluconate, lactate, carbonate and zinc sulfate can be used. Vitamin preparation: Vitami C is made liposoluble. Vit C esterifies a relatively long chain fatty acid such as pal mitic acid: Vit C is used here in the form of ascorbyl pal mitate, commonly available commercially. The vitamin E used is advantageously in the form of D-alpha-tocopherol acetate because used in high doses the non-esterified form then has a prooxidative effect. Being very viscous it is diluted in an oil, preferably a so-called "MCT" mixture of medium and short chain triglycerides C 8 -Cι 0 ; Vitamin E is in particular available from the company POLARIS under the trade name D-alpha-Tocopherol acetate. A natural antioxidant can be added such that a mixture containing at least 70% of tocopherols (rich in delta and gamma form). Such a product is available from the company POLARIS under the trade name Oxynat 70 I P. Preferably still, a chelating agent is added to the composition in an oily state such as soy lecithin (not GMO-I P ) for example. Such a product is available in particular from the company STERN under the name Sterncithine. The desired viscosity of the composition according to the invention is from 75 to 80 Mpa.s. A flavor can be added such as strawberry, caramel chocolate, strawberry chocolate, tutti frutti, banana or lemon. Such aromas are available from the company G IVAU DAN. The operations of mixing the various constituent elements of the composition are preferably carried out in avoiding any heating and advantageously under vacuum or under an inert atmosphere (nitrogen, argon). A typical composition comprises by weight per cent of the total composition: Zn 1.06% Cu 0.03% Vit C 23.93% Vit E 3.07% The optional additives or excipients are typically present at the rate of: Antioxidant 0.29% Aroma 1.07% MCT qs 1 00% Example 2: Oily form of the composition according to the invention comprising other active agents, in particular omega 3 and Vit. A, lutei ne, Zéaxanthi ne, and Séléiu m. To the oily composition as described in Example 1, the following other active ingredients are added: At least one polyunsatu fatty acid of the “Omega 3” type: thus docosahexaenoic acid (DHA), eicosapentaenoic acid ( EPA), alphalinolenic acid (ALA) alone or as a mixture. In the present invention, a mixture preferably containing 20-93% of DHA is added, the remainder being essentially formed of EPA. Such a product is available from POLARIS under the trade name EPAX 1 050 TG (1 0% EPA, 50% DHA). Vitami ne A: preferably to be added in the form of its precursor beta-carotene available in particular from the company ROCHE under the trade name Beta-carotene 30% FS or in the form of Vitaminate. A. Lutein is also added: it is in the form of a powder made liposoluble in a mixture of medium to medium triglycerides and short chains (MCT) prior to its addition. Such a product is in particular available from the company SOPRAL under the trade name Lutei n powder OS 24. Zeaxanthi ne: before being added to the mixture it is preferably dissolved in an alcohol, for example ethanol. Such a product is available from the company PIVEG under the trade name Zeaxanthin oil 20%. Selenium: trace element added in the form of particles of selected yeast powder suspended in oil. Such a product is available from QU IM DIS
SA sous la dénomination commerciale Lalmi n SE 2000. Antioxydants tels qu'u n mélange de tocophérols, tel le produit qui est disponible auprès de la société POLARIS sous la dénomi nation commerciale Oxynat 70 I P, ou le Coenzyme Q1 0, ou encore u n extrait de romari n , pré-émulsion nés de manière à être dispersibles dans l'huile. Agent chelateu r : lecithi ne déjà mentionnée ci-dessus. Com me excipients on peut citer les arômes déjà mentionnés ci-dessus. Sucres, à ajouter sous forme de sirop de glucose, fructose, formant une dispersion ou édulcorants, en particulier l'aspartameSA under the trade name Lalmi n SE 2000. Antioxidants such as a mixture of tocopherols, such as the product which is available from POLARIS under the trade name Oxynat 70 IP, or Coenzyme Q1 0, or an extract de romari n, pre-emulsion born so as to be dispersible in oil. Agent chelateu r: lecithi ne already mentioned above. As excipients, mention may be made of the aromas already mentioned above. Sugars, to be added in the form of glucose syrup, fructose, forming a dispersion or sweeteners, in particular aspartame
- avantageux chez le diabétique - sous forme de poudre miscible dans l'huile. Exemple de composition huileuse conforme à l'i nvention : Vit. C (palmitate d'ascorbyle) 23,93% Oméga 3 14,56% Vit. E (D-alpha-tocophérol) 3,07% Oxyde de zi nc (microencapsulé) 1 ,06% Vit. A (béta carotène) 0,47% Lutéine 0,31 % Oxyde de cuivre (microencapsulé) 0,03% Zéaxanthi ne 0,01 % Sélénium 0,01 % MCT 55, 1 9% Arôme fraise 1 ,07% Anti-oxydant 0,29% De manière générale, les pourcentages en poids pour cent de Vitamine C des constituants d'une composition typique selon l'invention sont les suivants : Cuivre 0,11% Zinc 4,42% Vit E 12,84% Vit A 1 ,98% et ceux des constituants optionnels, lorsqu'ils sont présents, sont les suivants : Oméga 3 60,83% Luthéine 1,31% Zéaxanthine 0,03% Sélénium 0,02% Anti-oxydant 1,21%- advantageous for diabetics - in the form of an oil miscible powder. Example of an oily composition in accordance with the invention: Vit. C (ascorbyl palmitate) 23.93% Omega 3 14.56% Vit. E (D-alpha-tocopherol) 3.07% Zinc oxide (microencapsulated) 1.06% Vit. A (beta carotene) 0.47% Lutein 0.31% Copper oxide (microencapsulated) 0.03% Zeaxanthi ne 0.01% Selenium 0.01% MCT 55, 1 9% Strawberry flavor 1.07% Antioxidant 0.29% In general, the percentages by weight percent of Vitamin C of the constituents of a typical composition according to the invention are as follows: Copper 0.11% Zinc 4.42 % Vit E 12.84% Vit A 1.98% and those of the optional constituents, when present, are as follows: Omega 3 60.83% Lutein 1.31% Zeaxanthin 0.03% Selenium 0.02% Antioxidant 1.21%
Exemple 3 : Forme de type émulsion aqueuse buvable de la composition conforme à l'invention On prépare l'émulsion comme suit : A une solution aqueuse comprenant tous les composés hydrosolubles est ajouté un émulsifiant tel que la lecithine et on verse sous forte agitation - par exemple, à l'aide d'un dispositif à 2 rotors tournant en sens inverse pour avoir un cisaillement fort - la composition huileuse de l'exemple 1 ou 2 à l'exception des microcapsules qui sont ajoutées ensuite et mélangées avec un brassage doux -par exemple avec un agitateur à pales. Taille des particules huileuses de 3 à 10 microns, de préférence de 4 à 6 microns. Au delà de 10 microns, il y a risque de coalescence. Une émulsion typique conforme à l'invention comprend : Phase aqueuse 30-40% Emulsifiant 3-7% Phase huileuse qsp 100% Dans la phase aqueuse, on peut ajouter avantageusement une gomme de type gomme guar, xanthane ou apparentées. L'ajout de la phase huileuse est réalisé sous agitation violente à l'aide d'u n homogeneisateu r type Ultratu rax ou équivalent. Les microcapsules ne sont ajoutées, sous agitation lente, qu'une fois l'émulsion réalisée.Example 3: Form of drinkable aqueous emulsion type of the composition in accordance with the invention The emulsion is prepared as follows: To an aqueous solution comprising all the water-soluble compounds is added an emulsifier such as lecithin and poured under vigorous stirring - by example, using a device with 2 rotors rotating in opposite directions to have a strong shear - the oily composition of example 1 or 2 with the exception of the microcapsules which are then added and mixed with a gentle stirring - for example with a paddle stirrer. Size of the oily particles from 3 to 10 microns, preferably from 4 to 6 microns. Beyond 10 microns, there is a risk of coalescence. A typical emulsion according to the invention comprises: Aqueous phase 30-40% Emulsifier 3-7% Oily phase qs 100% In the aqueous phase, it is advantageous to add a gum of the guar, xanthan or related gum type. The addition of the oily phase is carried out with vigorous stirring using a homogenizer such as Ultratu rax or equivalent. The microcapsules are only added, with slow stirring, once the emulsion has been produced.
Exemple 4 : Forme de type gel buvable de la composition conforme à l'invention 4.1 . Exemple d'u ne préparation d'u ne émulsion de type gel : 1 / Disperser de l'algi nate de sodium (1 %) dans l'eau sous forte agitation. 2/ Incorporer u ne émulsion comme celle préparée à l'exemple 3. 3/ I ncorporer une dispersion de sulfate de calciu m (1 %) dans la préparation . U n gel est obtenu . 4.2. Autre exemple Il est possible d'utiliser également des carraghénanes (0.5%) en solution dans l'eau et en présence de citrate de sodium (0.25%). Etapes de préparation d'u ne émulsion de type gel : 1 / Mélanger à sec les caraghénanes et le citrate de sodiu m. 2/ Disperser le mélange obtenu en 1 / dans l'eau sous forte agitation . 3/ Chauffer à 90 °C pou r solubiliser les caraghénanes. 4/ I ncorporer une émulsion, comme illustrée à l'exemple 3, tout en agitant sous gaz neutre ou sous vide. 5/ Mettre en chambre froide pou r gélifier et pou r éviter tout risque d'oxydation . 4.3. Autre exemple de gel : gel huileux Remplacer dans les préparations précédentes, telles qu'illustrées en 4.1 ou 4.2, l'émulsion par u ne huile. On effectue une agitation douce au moyen de pales. U n gel typique selon l'invention comprend : Eau 25-50% Algi nate de sodiu m 1 % Sulfate de calciu m 1 % Emulsion 48-73% A la place de l'émulsion on peut envisager d'i ncorporer l'huile, comme mention né précédemment.Example 4: Form of drinkable gel type of the composition in accordance with the invention 4.1. Example of a preparation of a gel type emulsion: 1 / Disperse sodium alginate (1%) in water with vigorous stirring. 2 / Incorporate an emulsion like that prepared in Example 3. 3 / I ncorporate a dispersion of calcium sulphate m (1%) in the preparation. A gel is obtained. 4.2. Another example It is possible to also use carrageenans (0.5%) in solution in water and in the presence of sodium citrate (0.25%). Steps to prepare a gel-type emulsion: 1 / Dry mix the carrageenans and soda citrate m. 2 / Disperse the mixture obtained in 1 / in water with vigorous stirring. 3 / Heat to 90 ° C to dissolve the carrageenans. 4 / Incorporate an emulsion, as illustrated in Example 3, while stirring under neutral gas or under vacuum. 5 / Put in a cold room to gel and to avoid any risk of oxidation. 4.3. Another example of gel: oily gel Replace in the previous preparations, as illustrated in 4.1 or 4.2, the emulsion with an oil. Soft agitation is carried out using blades. A typical gel according to the invention comprises: Water 25-50% Algi nate of sodiu m 1% Sulfate of calciu m 1% Emulsion 48-73% Instead of the emulsion one can consider incorporating the oil , as previously mentioned.
Exemple 5 : Préparation sèche pou r complément nutritionnel liquide buvable extemporané tel que toutes les formes de poudre(s), granulé(s), compri més hydrosolubles constituables extemporanés dans u n peu d'eau ou u n liquide. La composition de base est par exemple formée de : - Poudre de microcapsules d'oxyde de zi nc et de cuivre - Vit. E qui est microencapsulée par mise sous forme de poudre pulvérisée par nébulisation au-dessus d'u n support. Elle est préparée de préférence par adsorption su r un support de type silice amorphe su r laquelle on dépose ensuite la matière grasse d'encapsulation . - Vit C peut être ajoutée telle qu'elle ou sous forme microencapsulée ou bien sous forme de palmitate d'ascorbyle. - Oméga 3 : sont sous forme microencapsules et sont obtenus de préférence à parti r d'u ne émulsion comprenant oméga 3 dans l'eau , u n ou plusieu rs émulsifiants. Cette émulsion est ensuite séchée puis encapsulée. Pou r obteni r u ne poudre hydrosoluble, un procédé d'atomisation est appliqué su r u ne préparation spécifique ou émulsion à base d'huile et constituée d'au moins 40 % de forme sèche de caséinate. Ce mélange huileux initial peut conteni r dans les proportions déjà décrites pou r la forme liquide huileuse des oméga 3, des vitamines A et E et de la lutéine. Les actifs hydrosolubles de type vitamine C, lycopène, levure séléniée ou les oligoéléments comme le zinc et le cuivre (respectivement sous forme d'oxyde ou de gluconate) sont ajoutés ensuite à cette poudre dans les proportions déjà définies. L'atomisation consiste en l'injection sous pression par une buse de vaporisation, dans une enceinte chauffée par air puisé à 80° C au cœur, du mélange décrit ci-dessus. L'aromatisation du mélange pourra être obtenue soit par ajout d'une poudre d'aromatisation, soit par incorporation d'une huile aromatique au mélange huileux initial avant atomisation. Un tel produit est disponible auprès de la société POLARIS sous la dénomination commerciale omegacaps® DHA C. Example 5: Dry preparation for nutritional supplement drinkable liquid extemporaneous such as all forms of powder (s), granulate (s), water-soluble tablets constitutable extemporaneous in a little water or a liquid. The basic composition is for example formed from: - Powder of microcapsules of zinc oxide and of copper - Vit. E which is microencapsulated by putting in the form of powder sprayed by nebulization above a support. It is preferably prepared by adsorption on a support of the amorphous silica type on which the fatty encapsulation material is then deposited. - Vit C can be added as it is or in microencapsulated form or else in the form of ascorbyle palmitate. - Omega 3: are in microencapsule form and are preferably obtained from an emulsion comprising omega 3 in water, one or more emulsifiers. This emulsion is then dried and then encapsulated. To obtain a water-soluble powder, an atomization process is applied on a specific preparation or oil-based emulsion consisting of at least 40% dry form of caseinate. This initial oily mixture may contain in the proportions already described for the oily liquid form of omega 3, vitamins A and E and lutein. Assets water-soluble type vitamin C, lycopene, selenium yeast or trace elements such as zinc and copper (respectively in the form of oxide or gluconate) are then added to this powder in the proportions already defined. The atomization consists of the injection under pressure by a spray nozzle, into an enclosure heated by air drawn at 80 ° C. at the heart, of the mixture described above. The flavoring of the mixture can be obtained either by adding a flavoring powder, or by incorporating an aromatic oil into the initial oily mixture before spraying. Such a product is available from the POLARIS company under the trade name omegacaps® DHA C.

Claims

REVENDICATIONS 1 . Complément nutritionnel liquide caractérisé en ce qu'il consiste en une composition comportant u ne association de Cu (cuivre) et de Zn (zi nc) sous forme de microcapsules lipodispersibles dans un mélange de Vitamine E et de Vitami ne C. 2. Complément nutritionnel selon la revendication 1 , ladite composition comportant en outre au moins un actif ou additif choisi dans le groupe constitué par Vitami ne A, un acide gras polyi nsatu ré du type oméga 3, u n oligo-élément de type sélénium , un pigment rétinien carotenoïde tel que luthéi ne, zéaxanthi ne, méso-zéaxanthi ne, u n anti-oxydant, un agent chelateu r de type lecithi ne ou u n mélange quelconque de ceux-ci . 3. Complément nutrition nel selon la revendication 1 ou 2, ladite composition étant une huile. 4. Complément nutrition nel selon la revendication 1 ou 2, ladite composition étant u ne émulsion aqueuse. 5. Complément nutrition nel selon la revendication 1 ou 2, ladite composition étant u n gel. 6. Complément nutrition nel selon la revendication 1 ou 2, ladite composition étant sous forme de poudre sèche à réhydrater. 7. Complément nutritionnel selon la revendication 6 prise en combi naison avec la revendication 2, caractérisé en ce que la Vit E et oméga 3 sont microencapsules. 8. Complément nutrition nel selon l'une quelconque des revendications précédentes caractérisé en ce que les pou rcentages en poids pou r cent de Vitami ne C des constituants de ladite composition sont les suivants : Cuivre 0, 1 1 % Zinc 4,42% Vit E 12,84% Vit A 1 ,98% et ceux des constituants option nels, lorsqu'ils sont présents, sont les suivants : Oméga 3 60,83% Luthéine 1,31% Zéaxanthine 0,03% Sélénium 0,02% Anti-oxydant 1,21% 9. Procédé de préparation d'un complément nutritionnel liquide selon l'une quelconque des revendications 1 à 8, comprenant les étapes consistant à (i) préparer une association de Cu (cuivre) et de Zn (zinc) sous forme de microcapsules lipodispersibles et (ii) disperser la préparation ainsi obtenue dans un mélange de vitamine E et vitamine C. 10. Utilisation d'un complément nutritionnel selon l'une quelconque des revendications 1 à 8, ou obtenu par le procédé selon la revendication 9, dans la fabrication d'une préparation pour une administration entérale en gériatrie, ophtalmologie. 11. Utilisation selon la revendication 10 dans le traitement de la dégénérescence maculaire liée à l'âge, des rétinopathies pigmentaires et du vieillissement oculaire. CLAIMS 1. Liquid nutritional supplement characterized in that it consists of a composition comprising a combination of Cu (copper) and Zn (zi nc) in the form of lipodispersible microcapsules in a mixture of Vitamin E and Vitami ne C. 2. Nutritional supplement according to claim 1, said composition further comprising at least one active ingredient or additive chosen from the group consisting of Vitami ne A, a polyisnu fatty acid of the omega 3 type, a trace element of the selenium type, a carotenoid retinal pigment such as that lutei ne, zeaxanthi ne, meso-zeaxanthi ne, an antioxidant, a chelating agent of the lecithin type or any mixture of these. 3. Nutritional supplement according to claim 1 or 2, said composition being an oil. 4. Nutritional supplement according to claim 1 or 2, said composition being an aqueous emulsion. 5. Nutritional supplement according to claim 1 or 2, said composition being a gel. 6. Nutritional supplement according to claim 1 or 2, said composition being in the form of a dry powder to be rehydrated. 7. Nutritional supplement according to claim 6 taken in combination with claim 2, characterized in that Vit E and omega 3 are microencapsules. 8. Nutritional supplement according to any one of the preceding claims, characterized in that the weight percentages of Vitami ne C of the constituents of the said composition are as follows: Copper 0, 1 1% Zinc 4.42% Vit E 12.84% Vit A 1.98% and those of the optional constituents, when present, are as follows: Omega 3 60.83% Lutein 1.31% Zeaxanthin 0.03% Selenium 0.02% Antioxidant 1.21% 9. Process for the preparation of a liquid nutritional supplement according to any one of claims 1 to 8, comprising the steps of (i) preparing a combination of Cu (copper) and Zn (zinc) in the form of lipodispersible microcapsules and (ii) dispersing the preparation thus obtained in a mixture of vitamin E and vitamin C. 10. Use of 'a nutritional supplement according to any one of claims 1 to 8, or obtained by the method according to claim 9, in the manufacture of a preparation for enteral administration in geriatrics, ophthalmology. 11. Use according to claim 10 in the treatment of age-related macular degeneration, pigmentary retinopathies and ocular aging.
PCT/FR2005/050296 2004-05-07 2005-05-03 Liquid nutritional supplement and method for preparing same WO2005110114A1 (en)

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