DE212015000033U1 - Therapeutic astaxanthin and phospholipid - Google Patents

Abstract

Dietary supplement composition formulated in an amount effective to promote the maintenance of cardiovascular health comprising astaxanthin and a mixture of a phospholipidreichen roe extract and a seed oil extract comprising a ratio of alpha-linolenic acid (ALA) to linoleic acid (LA) is between 1: 1 and 6: 1.

Description

• Related Application (s)
• This application claims priority to US patent application Ser. 14 / 658.457, filed March 15, 2015 and US patent application Ser. 14 / 219.484, filed March 19, 2014.
• Field of the Invention
• This invention relates to compositions using astaxanthin and phospholipids, to treat humans.
• Background of the Invention
• The use of krill oil and / or marine oil is in the US Patent Publication Nos. 2004/0234587 ; 2004/0241249 ; and 2007/0098808 disclosed, the disclosures of which are hereby fully incorporated by reference, and in the related U.S. patent applications, Ser. 12 / 840.372 and 13 / 079,238 discussed. The advantageous aspects of the use of krill oil and / or marine oil are also shown in a research paper published by , The disclosure of which is hereby fully incorporated by reference.
• the published '587 - '249 - and '808 Logins discuss the advantageous aspects of the use of krill oil in association with pharmaceutically acceptable carriers. For example, this krill oil and / or marine oil can be obtained by combining individual steps as described in '808 -Registration taught by Krill and / or marine material are placed in a ketone solvent, a first lipid rich fraction from the liquid fraction is recovered by evaporation whereby the liquid and the solids are separated, the solids fraction and an organic solvent in an organic solvent of type are arranged, as taught in the description, whereby the liquid portion and the solid portion separated by a second lipid rich fraction by evaporation of the solvent is recovered from the liquid fraction and by the solid content is obtained. The resulting krill oil extract was used in an attempt to lower lipid profiles in patients with hyperlipidemia. The '808 -Publishing leads to details concerning this krill oil, which is produced using the above-identified general steps.
• Summary of the Invention
• Commonly assigned preceding parent applications and the parent applications US Patent Nos. 8,663,704 and 8,728,531 , The disclosures of which are hereby fully incorporated by reference, are directed to the advantageous use of krill oil and astaxanthin for the treatment of LDL oxidation (oxidation of low density lipoprotein (LDL)). The use of krill oil was a focus of '704 - and '531 Patents. The development has been achieved with various algae species that produce only EPA or EPA and DHA (docosahexaenoic acid). The development was achieved using Phospholipidquellen and a roe extract and other surfactants.
• A dietary supplement composition includes a therapeutic amount of astaxanthin and at least one of a phospholipid, glycolipid and sphingolipid, and is formulated in an oral dosage form. The astaxanthin makes up 0.1 to 15 weight percent of at least one phospholipid, glycolipid and sphingolipid. The astaxanthin may be derived, in one example of a synthetic or natural or a synthetic ester diol. In another example, the dietary supplement composition is formulated to treat cardiovascular disease, disorder or impairment in humans. In another example, it is formulated to treat a neurological disease, disorder or impairment in humans. In another example, it is formulated to treat a cognitive disease, disorder or impairment in humans or a dermatological disease, disorder or impairment to treat humans. It can be formulated to treat an inflammatory joint disease, jam or debuff or joint pain in humans.
• The dietary supplement composition may contain a diluent in pharmaceutical quality or food quality. The phospholipid may include, in one example at least one of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine. The phospholipid may be derived from at least one of a vegetable source, a seaweed source and an animal source or a synthetic derivative. The composition may contain from 0.5 to 12 mg astaxanthin and 50 to 500 mg of at least one phospholipid, glycolipid and sphingolipid. The dietary supplement composition can be formulated in a single dose capsule.
• In another example, the dietary supplement composition comprises a therapeutic amount of astaxanthin, which is derived from a synthetic ester or diol, and at least one of a phospholipid, glycolipid and sphingolipid, and is formulated in an oral dosage form. The astaxanthin makes up 0.1 to 15 weight percent of at least one phospholipid, glycolipid and sphingolipid. The composition is formulated to treat LDL oxidation in humans.
• A method for the treatment of LDL oxidation in humans comprises administering a therapeutic amount of a dietary supplement composition comprising 0.5 to 12 mg astaxanthin derived from a synthetic ester or diol, and at least one phospholipid, glycolipid and sphingolipid, and is in an oral dosage form formulated, wherein the astaxanthin of the constitutes from 0.1 to 15 weight percent of at least one phospholipid, glycolipid and sphingolipid.
• Detailed Description of the Preferred Embodiments
• The present invention will now be described in more detail in the following, preferred embodiments of the invention are described. However, the present invention can be presented in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and to the skilled person to convey the scope of the invention completely.
• The following is a description of the dietary supplement composition and related method used to improve blood lipid profiles and to LDL peroxidation reduce humans, discussed in the preceding parent applications and the parent applications '704 - and '531 -Patentschriften, which are disclosed in these patents, followed by further details of a phospholipid and then a description of the oil derived from seaweed and its composition with phospholipid and glycolipid-bound EPA or EPA and DHA. The description will proceed to details of the disclosure in the '704 - and '531 -Patentschriften, in view of the use of Kill oil, which is included in the composition, continued and then continued with the description and the details of the phospholipid-enriched delivery mechanism for astaxanthin and then the oil derived from algae. Some of the components of the composition are changing, such as the levels of EPA and / or DHA and EPA, and other components when the oil extracted from algae is used, as will be shown later in various tables in the following description.
• The composition, the krill oil on the disclosure of the parent application and the previous parent application '704 - and '531 refers -Patentschriften containing EPA and DHA, functionalized as marine phospholipids and Acyltriglyceride derived from krill. A krill, algae, Rogenextrakt-, fish oil, and phospholipid in accordance with one non-limiting example, however, can comprise natural or synthetic or esterified diol from a synthetic astaxanthin. It has been found that a new and potentially quite important biomarker for cardiovascular risk with the amount of EPA and DHA, which is found in red blood cells divided by the total fatty acid content in red blood cells or the so-called "omega-3 index" related , The compositions according to one non-limiting example, improve the omega-3 index in humans with prolonged administration and it is therefore assumed that they reduce risk for a cardiovascular event. Some of these components that relate to the krill oil are explained in the following table:

  components	Percentage (%)
  PHOSPHOLIPIDS
  PC, PE, PI, PS, S, CL	> 40
  OMEGA-3 (functionalized on PL)	> 30
  Eicosapentaenoic acid (EPA) *	> 17 (15% in one example, and 10% in another)
  Docosahexaenoic acid (DHA) +	> 11 (9% in one example, and 5% in another)
  ANTIOXIDANTS	(Mg / 100g)
  Astaxanthin, vitamin A, vitamin E	> 01.25

  *> 55% of PL EPA / GesamtEPA
  +> 55% of PL DHA / total DHA
  These amounts may vary depending on the application and the people.
• The krill oil or oil derived from seaweed and other phospholipids, such as are disclosed, enriched with astaxanthin to enhance the usefulness of the formulated product. In a study led 4 mg astaxanthin per day for two weeks to a 26% reduction in LDL cholesterol oxidation. 4 mg astaxanthin for eight weeks resulted in a 21% reduction in the values ​​for C-reactive protein. showed 3.6 mg astaxanthin per day for two weeks that astaxanthin LDL cholesterol protects against induced in vitro oxidation.
• Astaxanthin the blood levels of C-reactive protein (C-RP) is also known to reduce in vivo. For example, a three-month astaxanthin treatment resulted in human subjects with high risk levels of C-RP in a 43% drop of serum C-RP levels in the patient population, a decrease which is below the level of risk for an unacceptable cardiovascular event. Astaxanthin is so potent that it has been shown that it was the pro-oxidant activity of Vioxx, a COX-2 inhibitor, which belongs to the class of drugs NSAIDS, cancels in vitro, which is known that it causes cell membrane lipid peroxidation leading to heart attacks leads and strokes. For this reason Vioxx was subsequently taken by the FDA from the US market.
• Astaxanthin is absorbed in vitro also in lens epithelial cells where it lipid peroxidation vermittele cell damage with umol / L concentrations suppressed UVB-induced. The reduction of C-reactive protein (CRP), the reduction of LDL oxidation and an increase in omega-3 index in vivo would probably deliver all an important positive contribution to cardiovascular health, as it is for all to well-known biomarker is for cardiovascular health risks. These results were shown in:
• 1) ;
• 2) ;
• 3) ; and
• 4) ,
• The composition contains 300-500 mg of krill oil or a product obtained from algae oil and 2 mg astaxanthin. Up to 8 mg and 12 mg may be used in some instances. It can contain 300 to 500 mg of at least one phospholipid, glycolipid and sphingolipid.
• Krill oil is usually from Antarctic krill (Euphausia superba) produced, which is a zooplankton (the basis of the food chain). It is one of the most abundant marine biomass, according to some estimates, about 500 million tons. Krill breed in the pure, uncontaminated deep waters. It is an unused marine biomass and the catch per year according to some estimates is less than or equal to about 0.02%.
• It is believed that the krill oil-based phospholipid-bound EPA and -DHA uptake in cell membranes is far more efficient than Triacylglyercid-bound EPA and DHA, as the conversion of triacylglycerols in the liver is inefficient in itself and because phospholipid Specific kinds EPA and DHA can be transported into the blood stream via the lympathische system, thereby preventing degradation in the liver. In addition, the consumption of krill oil no regurgitation, which is observed with fish based oil products produced. Because of this burp-characteristic of fish oils, it was found that about 50% of consumers who try fish oil, never buy it again.
• The safety standard of astaxanthin is excellent. A study produced the following results:
• Oral LD ​​50: 600 mg / kg (rat);
• NOAEL: 465 mg / kg (rat); or
• Serumpharmakokinetik:
• 1) T _1/2: 16 hours;
• 2) T _max: 8 hours;
• 3) C _max: 65 g / l.
• After eight weeks of supplementation with 6 mg per day, there was no negative effect on healthy adults. ,
• In one non-limiting example, astaxanthin has three major sources. 3 mg astaxanthin per 240g portion of non-breeding salmon or 1% to 12% astaxanthin oleoresin or 1.5-2.5% of microalgae beads produced. References that are relevant to the discussion above, can be found in ; ; ; and , Reports 1 and 2. FIG.
• Many beneficial and synergistic effects that are here now reports have been observed when krill oil especially if krill oil is used in combination with astaxanthin in combination with other active ingredients, and in one example. It should be understood that different proportions of ingredients and percentages in compositions may be used depending on the end use and other environmental factors and physiological factors in a patient's condition is treated.
• The krill oil is an example from Euphausia spp. originate comprising eicosapentaenoic (EPA) - and docosahexaenoic (DHA) fatty acids in the form of triacylglycerols and phospholipids, but not less than 1% EPA and 5% DHA have been found to be advantageous. In another example, the krill oil comprises at least 15% EPA and 9% DHA, of which not less than 45% in the form of phospholipids and, in one example more than 50%. The composition can be given for therapeutic results with 1-4000 mg krill oil advantageously as a daily dose. In another example, 0.1-50 mg astaxanthin per daily dose to be added to the krill oil, and in one example, 0.1-12 mg astaxanthin.
• The astaxanthin is derived from Haematococcus pluvialis-algae, Pfaffia, krill or synthetic pathways in the known free diol, monoester or diester form and in one example in a daily dose of 0.5-8 mg. If this amount of astaxanthin, especially when it comes from Haematococcus pluvialis, derived oil is applied to a range of 300-500 mg krill oil or from algae, the numerical range of about 0.1 to 2.7 parts by weight percent of the krill oil or is from obtain algae oil produced.
• The composition may also contain a fatty acid rich n-3 oil (omega-3) derived from fish oil, algae oil, linseed oil or Chiasamenöl when the n-3 fatty acid source alpha-linolenic, stearidonic, eicosapentaenoic acid or docosapentaenoic acid comprising. The composition may comprise originating from the natural and synthetic antioxidants, which are added to retard the degradation of fatty acids and astaxanthin.
• For details on the method of CO2 extraction and processing technology (such as supercritical CO2 extraction) and the Peroxidationsblockertechnologie that can be used are described in commonly assigned US Patent No. publish. 2009/0181127 ; 2009/0181114 ; and 2009/0258081 discloses the disclosures of which are hereby incorporated by reference ENTIRE.
• As mentioned above, there are beneficial aspects of using krill oil or oil derived from seaweed in synergistic combination with other ingredients. It has also been determined that derived from fish oil, based on choline, phospholipid-bound omega-3 fatty acid mixture including phospholipid-bound polyunsaturated EPA and DHA, is also advantageous in order to improve blood lipid profiles and reduce LDL, either alone or mixed with other ingredients, for example, an LDL Peroxidationsblocker. A commercially available example of a mixture of a derived from fish oil-based choline, phospholipid gebundenden fatty acid mixture, including polyunsaturated EPA and DHA, is Omega Choline 1520F as a phospholipid, omega-3 composition which is derived from natural fish oil, and Enzymotec Ltd is sold. An example of such a composition is described below. Ingredients (g / 100g):

  pure marine phospholipids	not less than (NLT) 15
  DHA *	(NLT) 12
  EPA **	(Nlt) 7

  * docosahexaenoic acid
  ** eicosapentaenoic acid

  Omega 3	(NLT) 22
  Omega-6	<3

  Analytical data:

  Peroxide Value (meq / kg)	(NMT) not more than 5
  Loss on drying (g / 100g)	(NMT) 2

  Physical Properties:

  consistency

  viscous liquid

• According to a non-limiting example, the method improves blood lipid profiles and either alone or in combination with added astaxanthin, such as a Peroxidationsblocker, and reduced LDL oxidation in a patient by administering a therapeutic amount of a composition consisting of a derived a mixture of fish oil, choline-based, phospholipid-bound omega-3 fatty acid mixture containing phospholipid-Specific kinds polyunsaturated EPA and DHA, either alone or as a mixture with an LDL Peroxidationsblocker such as astaxanthin. In one example, the composition in combination with astaxanthin in an oral dosage form is administered. The mixture of the derived from fish oil-based choline, phospholipid-bound fatty acid mixture containing polyunsaturated EPA and DHA, in one example comprises eicosapentaenoic acid (EPA) - and docosahexaenoic (DHA) fatty acids in the form of triacylglycerols and phospholipids. In another example, the omega-choline containing at least 7% EPA and 12% DHA, of which not less than 15% are in the form of phospholipids. The composition may be given advantageously for therapeutic results with 1-4000 mg of a mixture of fish oil and derived from fish oil-based choline, phospholipid-bound fatty acid mixture containing polyunsaturated EPA and DHA per daily dose. In another example, 0.1-20 mg astaxanthin are added to the omega-choline per daily dose.
• It should be understood that a present formulation can be used for LDL reduction, if it uses only a mixture of one derived from fish oil-based choline, phospholipid-bound fatty acid mixture containing polyunsaturated EPA and DHA. It is also possible to use a mixture of one derived from fish oil, based on choline, phospholipid-bound omega-3 fatty acid mixture (including polyunsaturated EPA and DHA), mixed with astaxanthin to use. It should also be understood that an enriched version of a mixture originating from a fish oil, based on choline, phospholipid-bound fatty acid mixture containing polyunsaturated EPA and DHA, can be used wherein the fraction of the added fish oil diluent was reduced and the proportion was increased derived from fish oil phospholipids. This can be achieved by using supercritical CO2 extraction and / or solvent extraction to selectively remove phospholipids from triacylglycerides. The composition may also include a natural or synthetic cyclooxygenase-1 or -2 inhibitors, including, for example, aspirin, acetaminophen, steroids, prednisone or NSAIDs. The composition may also include a gamma-linoleic acid-rich oil, comprising borage (Borago officinalis L) or safflower (Carthamus tinctorius L) that provides a metabolic precursor for PGE ₁ synthesis, included.
• The composition may also contain a fatty acid rich n-3 oil (omega-3) derived from fish oil, algae oil, linseed oil, Chiasamenöl or Perillasamenöl, wherein the n-3 fatty acid source alpha-linolenic, stearidonic, eicosapentaenoic acid or docosapentaenoic includes. The composition may comprise from nature-derived and synthetic antioxidants, which are added to retard the degradation of fatty acids, such as tocopherols, tocotrienols, carnosic acid or carnosol and / or astaxanthin.
• It has been found that high doses of astaxanthin alone are effective to treat osteoarthritis and joint pain. For example, used a clinical trial, such as disclosed in commonly assigned US Pat. No. 8,481,072 will be described, the disclosure of which is hereby fully incorporated by reference, 15 mg astaxanthin. It has now been determined that lower doses of astaxanthin instead of much higher dosages such as 15 mg, as can be in some clinical trials for osteoarthritis or other applications, including cardiovascular treatment, used provided their least one of a phospholipid, glycolipid and sphingolipid or other phospholipids was added. A diluent in pharmaceutical grade or food grade or other surfactant may be added. Other advantageous and often synergistic results are obtained when astaxanthin is used in the presence of other components, including hyaluronic acid with low molecular weight or UC-II. Phospholipids can obtained from plant phospholipids such as lecithin and lysophospholipids and / or glycophospholipids, including perilla contain, as in commonly assigned US Pat. No. 8,784,904 the disclosure of which is hereby fully incorporated by reference. Astaxanthinspiegel may vary from 0.5-2 mg and 0.5-4 mg and amount in one embodiment, 2-4 mg or 2-6 mg and up to 0.5-12 mg, and 7-12 mg.
• It has also proved to be advantageous to use herring roe extract as a source of phospholipids which have some EPA and DHA. This gives synergistic results and tremendous improvements observed. One study showed that phospholipids from herring roe improved the phospholipid and glucose tolerance in healthy young adults, as of released. The pure Rogenphospholipid can be used using extraction techniques. It is a honey-like product, which is made thinner in an example with fish oil and / or perilla oil or other oil seed or plant, or diluted.
• The specification before dilution with fish oil and / or perilla is as follows:

  Percentage which is phospholipids	60
  Phospholipid mg / g	600
  Phosphatidylcholine content mg ​​/ g	520
  Choline equivalents	83
  Total EPA mg / g (TG and PL-bound)	75
  Total DHA mg / g (TG and PL-bound)	195
  EPA mg / g, bound to phospholipid	67
  DHA mg / g, bound to phospholipid	175
  EPA + DHA mg / g, bound to phospholipid	242

• The herring roe extract is processed in one example, using ethanol extraction. Triacylglycerols are added and stripped with ethanol to have a robust solution. Oil seeds, such as the Perillasamenöl, taken as in the reference by '904 -Patentschrift described, can be returned to the ethanol extract before it is stripped for dilution and a mixture of forms with a high phospholipid content. The roe extract oil can with fish oil and / or seed oil such as perilla, or any other marine oil are mixed. 1, and preferably with up to 6: In one example, the herring roe extract with Perillasamenöl at least 1 is 1 ALA mixed to LA, wherein the concentrate contains at least 50%, and in another example, 60% phospholipids and in another example at least 30% and in a having another example, 40% triglycerides.
• An exemplary composition includes a combination of a roe extract of herring or a phospholipidreichen roe extract with phospholipid-bound EPA and DHA as a mixture with seed / fish oil and / or oil, wherein the seed oil has a ratio of ALA to LA between 1: 1 and 1: having 6, and in one example about 2-4 mg or 0.5 to 12 mg astaxanthin or other areas as mentioned above, contains. The amount of roe extract, with the oil such as perilla oil is mixed varies, and is about 150 to 500 mg or 300 to 500 mg or up to 1000 mg daily dose in one example and may contain hyaluronic acid. Other plant-based phospholipids may be used, including commercially available lecithins and a Eidotterderivat, including lysophospholipids and glycophospholipids which act as surfactants. It is possible to use on sunflower-based phospholipids and natural plant-based oils and natural Tensidextrakte. The astaxanthin is improved with fats, surfactants or phospholipids, and may also be made more efficient with phospholipids and on sunflower-based and / or the lipophilic perilla oil, as described above.
• 1: In one example, the perilla oil as a durable, with supercritical CO ₂ fluid extracted seed oil frutescens comes from a broken biomass from Perilla, with 60 to 95 percent (w / w) PUFAs in a ratio of 4: 1 to 6 alpha-linolenic acid (ALA) formed to linoleic acid (LA). The product derived from Perilla frutescens seed oil is prepared in one example, by the Perilla frutescens-seeds a supercritical CO2 fluid extraction is subjected to produce a seed oil extract; the resulting seed oil extract is fractionated in separate pressure reduction stages to collect light and heavy fractions of the seed oil extract; and the heavy fraction is separated from the light fraction to form the finished seed oil from the heavy fraction.
• Selected anti-oxidants are added in another example, and perilla oil containing a mixture of selected lipophilic and hydrophilic antioxidants. Lipophilic antioxidants may be used alone or in combination with at least one of: a) phenolic antioxidants, including at least one of sage, oregano, and rosemary; b) tocopherol; c) tocotrienol (s); d) carotenoids, including at least one of astaxanthin, lutein and zeaxanthin; e) ascorbyl acetate; f) ascorbyl palmitate; g) butylated hydroxytoluene (BHT); h) docosapentaenoic acid (BHA); or i) tertiary butylhydroquinone (TBHQ) can be used. A hydrophilic antioxidant or sequestering agent may hydrophilic phenolic antioxidants, including at least one of contain grape seed extract, tea extracts, ascorbic acid, citric acid, tartaric acid and malic acid.
• In one example, a peroxide value of this Perillasamenöls is below 10.0 meq / km. In another example of this Perillasamenöl has 85 to 95 percent (w / w) and PUFAs The PUFAs are to be at least more than 56 percent alpha-linolenic acid (ALA). The Perillasamenöl is stable at room temperature up to 32 months. In another example of this Perillasamenöl comes from a pre-ground or rolled into flakes chipped biomass of Perilla frutescens. The mixture of selected antioxidants may contain astaxanthin, phenolic antioxidants and natural tocopherols. The Perillasamenöl may also contain at least one of dispersed nanoparticles and microparticles of recovered from rice or sugar cane polycosanol.
• In one example, the composition is encapsulated in a single dose capsule and referred to as deep-sea caviar capsule. In a specific example, the encapsulated composition Heringkaviarphospholipidextrakt contains (herring roe), perilla seed extract {Perilla frutescens), olive oil, Zanthin ^® astaxanthin (Haematococcus pluvialis alga extract), gelatin, spice extract natural non-GMO-tocopherols, cholecalciferol, riboflavin, and Methylcobalamin. The composition includes fish like herring roe and tilapia gelatin. It can contain hyaluronic acid with low molecular weight as an additive for joint care. In the following table an example is set forth. Properties:

  Appearance	clear capsule size 00 with dark red, oily filling
  fatty acids
  ALA	minute 140 mg
  EPA	minute 18 mg
  DHA	minute 50 mg
  Total Omega-3	minute 210 mg
  phospholipids	195 mg
  astaxanthin	500 ug
  Vitamin D 3	1000 IU; 250% DV
  Vitamin B 2 (Riboflavin)	1.7 mg; 100% DV
  Vitamin B 12	6 .mu.g; 100% DV
  microbiology	USP <61> / FDA BAM
  Bioburden	<1000 cfu / g
  yeast and	<100 cfu / g
  molds
  E. coli	absent in 10 g
  Salmonella	absent in 10 g
  S. aureus	absent in 10 g
  storage
  conditions	sealed container, 15-30 ° C, 30-50% RH
  durability	at least 24 months
  packaging	(TBD number) HDPE or PET bottle

  All ingredients are BSE-free and GMO-free
• The processing components may include a mixture of marine omega-3 phospholipids derived from herring caviar, and contain Perillasamenöl. You can have a O2B ^TM botanical Peroxidationsblocker, including spice extract, non-GMO-tocopherols and ascorbyl contain. You can bulk in tightly sealed barrels, 45 and 190 kg net, are packed with inert head space corresponding to the European and American standards for food products. They are preferably stored below room temperature. The product is protected from light and heat. If the barrels are open for sampling, the head space during the sampling, and before the storage can be flushed with inert gas.

  test	unit	acceptance criterion		method
  Appearance		amber viscous oil		AM2020
  solubility		Oil-soluble and water-dispersible		AM2021
  		Minimal	Maximum
  ALA (C18: 3 n-3)	mg / g as TG 3)	230		AM1044
  ALA (C20: 5 n-3)	mg / g as TG 3)	30		AM1001
  DHA (C22: 6 n-3)	mg / g as TG 3)	85		AM1001
  Total omega-3 1)	mg / g as TG 3)	370		AM1001
  ALA (C18: 3 n-3)	mg / g FFA than 4)	215		AM1044
  ALA (C20: 5 n-3)	mg / g FFA than 4)	28		AM1001
  DHA (C22: 6 n-3)	mg / g FFA than 4)	80		AM1001
  Total omega-3 1)	mg / g FFA than 4)	335		AM1001
  Total PC	mg / g	250		AM1002
  Overall PL	mg / g	300		AM1002
  total neutral lipids	mg / g		700	AM1003
  Water content Karl Fisher medium	%		3.0	AM1004
  peroxide	meq / kg		10.0	AM1005
  Heavy metals (total of Pb, Hg, Cd inorganic As) 2)	mg / kg		10	AM1015

  1) total n-3: ALA, EPA, DHA, 18: 4, 20: 4, 21: 5, 22: 5
  2) frequency analysis
  3) all ALA, EPA, DHA or total omega-3 expressed as triglycerides
  4) all ALA, EPA, DHA or total omega-3 fatty acids expressed as free
• It was surprisingly found that the bioavailability of astaxanthin can be increased when it is in at least one of phospholipid, glycolipid and sphingolipid and optionally integrated in diluents in food grade and / or pharmaceutical grade, or is used with these. There are lower dosages compared to the 15 mg, which were used in previous clinical trials against joint pain, used as the phospholipid enhances delivery. The astaxanthin makes up at least about 0.1 to about 15 weight percent of the at least one phospholipid, glycolipid and sphingolipid. The astaxanthin is derived, in one example of a natural or synthetic ester or a synthetic diol. A diluent in pharmaceutical or food grade can be added. It can be used to treat various disorders, including cardiovascular, neurological, cognitive, dermatological diseases, disorders or impairments and problems with joint pain. If it is integrated in a microbiologically fermented hyaluronic acid having low molecular weight or in sodium hyaluronate (hyaluronan), as already described, a food supplement composition is formed and can be formulated in a therapeutic amount to treat symptoms of joint pain in a person who has the joint to treat and improve.
• It should be understood that the triglycerides have two types of molecules, ie a glycerol and three fatty acids, while although the phospholipids contain glycerol and fatty acids, but have a glycerol molecule and two fatty acid molecules. Instead of this third fatty acid is a polar group is instead attached to the glycerol molecule, so that the phospholipids compared with triglycerides hydrophobic, partially hydrophilic are. Lysophospholipids can be used as a derivative of a phospholipid, wherein one or both of acyl derivatives were removed by hydrolysis. Lecithin and its derivatives can be used as an emulsifier and surfactant as a wetting agent to reduce the surface tension of liquids. It can be used other phospholipids. Various phospholipids include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine. Some may be derived from egg yolk and be chemically extracted using hexane, ethanol, acetone, petroleum ether or benzene, and also mechanical, including from various sources, such as soybean, eggs, milk, marine sources and sunflower are extracted. If they come from soy and sunflower, the phospholipids may contain the above products, including phosphatidic. Various compositions, such as lecithin may be hydrolyzed enzymatically and among them, a fatty acid is removed by phospholipase to form the lysophospholipids, which, as explained above, can be added to the roe extract. A phospholipase is phospholipase A2, wherein the fatty acid is located at the C2-position of glycerol. Fractionation may be used.
• The glycolipids are mainly derivatives of ceramides, a fatty acid associated with the aminoalcohol sphingosine or linked. It should be understood that the phospholipid sphingomyelin is also from a ceramide. Glycolipids contained compared to the phospholipids but no phosphates. The fat is linked to a glycolipid with a sugar molecule and the fats are linked to sugar. Since it is composed of a sphingosine, fat and sugar, it is called by some glycosphingolipid. A sphingolipid is a lipid containing a backbone to Sphingoidbasis and a group of aliphatic amino alcohols, which contain the sphingosine. As noted above, the phospholipid and other components of at least one from a plant source, algae source and animal source, or a synthetic derivative can be derived. The phospholipid and other components can be made of at least one of soybean, sunflower, grapeseed, egg yolks, krill, fish body, fish roe, squid and algae derived. The phospholipid and other components may be formed as a connection-rich mono- or diglycerides or fatty acids, wherein the fatty acid between 2 and 20 carbon atoms. During processing, the composition is formed by the astaxanthin and phospholipid, and optionally a diluent are dispersed under high shear conditions. The diluent may be a diluent in pharmaceutical quality or food quality, as it is known in the art.
• In another example, the astaxanthin makes up about 2 to about 10 percent by weight of the phospholipid and glycolipid and derived from a natural or synthetic ester or a synthetic diol. In another example, 50 to 500 mg of phospholipid, glycolipid and sphingolipid can be used. The dietary supplement composition can be formulated in a single dose capsule.
• The astaxanthin may be made of Haematococcus pluvialis-algae, Pfaffia, krill or from synthetic pathways in free or synthetic diol, monoester or diester, both naturally derived and synthetically, with a daily dose of 0.5-8 mg, or 0, 5-12 mg, in one example and in another example 1-2 mg, 2-4 mg, 1-6 mg, and other fields, and up to 12 mg, including 7-12 mg.
• The astaxanthin may be between 2 to 4 mg or 0.5 to 12 mg and other fields, as disclosed above, vary. It should be understood that the astaxanthin and the at least one phospholipid, glycolipid and sphingolipid or other components, as described above, can be used for many different purposes and results. It can be used to support the treatment or improvement of blood lipid profiles and reduce LDL peroxidation in humans. It can be used to counter depression and other neurological disorders or treat. It can be used against respiratory diseases and skin disorders or diseases.
• The composition may also include a fatty acid rich n-3 oil (omega-3) derived from fish oil, algae oil, linseed oil, or Chiasamenöl Perillasamenöl contain. In one example, the n-3 fatty acid alpha-linolenic, stearidonic, eicosapentaenoic acid or docosapentaenoic acid comprising. In one example, the composition is as mentioned above. It has been found that a product obtained from algae oil can be used instead of krill oil. Hydrolyzed or not hydrolyzed collagen and elastin, which come from eggshell membranes can advantageously be used. The composition may also anti-inflammatory and / or natural joint health contain enhancing compounds comprising at least one of the preparations of green lipped mussel (Perna canaliculus), Boswellia serrata, turmeric (Curcuma longa), stinging nettle (Urtica dioica), Andrographis, Cat's Claw (Uncaria tomentosa) , bromelain, methylsulfonylmethane {MSM), chondroitin sulfate, glucosamine, s-adenosylmethionine, proanthocyanidins, procyanidins or flavonoids. The composition may comprise originating from the natural and synthetic antioxidants, which are added to retard the degradation of fatty acids and astaxanthin.
• It is also possible, a pure diol of S, S'-astaxanthin, including a synthetic diol with the surfactant and / or phospholipid to be used. It is possible to use the pure diol in combination as described above with the EPA-rich extracted from algae oil or other fish oil, roe extract or a plant-based oil and / or phospholipid and / or surfactant, and either with astaxanthin derived from Haematococcus pluvialis, or the free diol form in substantially pure S, S'-enantiomeric form is mixed. It is possible to add synthesis, mixed enantiomers of the diol. The diol of S, S 'astaxanthin is possible because there are oils and manufactured in the case of krill oil and algae and Hp phospholipids and other species, essentially diesters or Monoester with very little diol is insoluble. Some research shows that the bioavailability can be better by far than that of the monoester or diester. It is possible the pure S to synthesize S 'diol asymmetrical. Despite the poor solubility in some examples of pure diol, there may be an active transport mechanism associated with its bioavailability or vice versa, that the monoester or Diesterformen be transmitted only in the diol form from the intestine into the blood. comprising, based on phospholipid or glycolipid product, the EPA and / or DHA, together with the added astaxanthin in its various forms and in particular the S, S'-enantiomeric form in substantially Monoesterform from Haematococcus pluvialis or pure diol form from the asymmetric synthesis could be useful his. It is therefore possible to combine it with the derived from algae glycol and the phospholipid-based EPA-rich oil.
• As mentioned above, astaxanthin (3,3'-dihydroxy-β-β-carotene-4,4'-dione) is a xanthophyll carotenoid that is found in many marine species, including crustaceans Salmonidae and algae. Astaxanthin can not be synthesized by mammals, but works when it is taken with food, as an antioxidant, anti-inflammatory agent and has benefits for eye health, heart health and the immune system.
• Astaxanthin has a hydroxyl group at any of β-ionone unit, so it can be used in its free form (diol) as well as mono- or di-esterified be found. In natural products astaxanthin is usually present as a mixture: mainly Monoester of C12-C18 fatty acids and small amounts of diesters and free diol. Synthetic astaxanthin is usually found only in the free diol form available.
• The astaxanthin molecule has two chiral E / Z centers and three optical R / S-isomers. Haematococcus pluvialis-algae produce natural astaxanthin only as (3S, 3'S) -isomer. This is where Explained, the disclosure of which is hereby fully incorporated by reference.
• Alternatively, the yeast Phaffia rhodozyma synthesized only the 3R, 3'R configuration. This is where Explained, the disclosure of which is hereby fully incorporated by reference.
• Wild salmon contains predominantly the (3S, 3'S) -form with a (3S, 3'S) -, (3R, 3'S) - and (3R, 3'R) -Isomerverhältnis of 22: 1: 5. This is where Explained, the disclosure of which is hereby fully incorporated by reference up close.
• However, astaxanthin is produced by conventional synthesis, a racemic mixture of a (3S, 3'S) -, (3R, 3'S; meso) -, {3R, 3'R) ratio of 1: contain 1: 2. This ratio is also observed in many shrimp species that are capable of (3S, 3'S) to be racemized in the meso-form. This is where Explained, the disclosure of which is hereby fully incorporated by reference up close.
• However, most astaxanthin is in shrimp in the tank (cup), so that limited quantities of the meso isomer are recorded with the human diet.
• Feeding studies have shown that free fatty acid ester of astaxanthin diol or increase the amount of astaxanthin in human plasma. This is where ; and the Explained, the disclosures of which are hereby fully incorporated by reference.
• The uptake of free Astaxanthindiol is about 4-5 times higher than that of esterified astaxanthin, which is probably due to the limitation of the required enzymatic hydrolysis in the gut prior to absorption. These intestinal enzymes may be on astaxanthin and R / S-selective. found a higher relative absorption of astaxanthin from (3R, 3'R Astaxanthindipalmitat compared to the other two isomers. However, the consumption of racemic diol free astaxanthin showed no stereospecific selection.
• Astaxanthin for use in food supplements for humans is currently produced from the cultured freshwater algae Haematococcus pluvialis. These algae produce 3S, 3'S astaxanthin in a fatty acid matrix, which can be by solvent extraction or carbon dioxide isolated. The oily extract can be directly used in edible formulations, or be further processed into solid powders or beads formulations. Many clinical studies have been conducted with derived from H. pluvialis astaxanthin to demonstrate the beneficial effects on health and safety. Food additive approvals for astaxanthin-rich algae extracts have been authorized for many suppliers in the US and the EU.
• The Haematococcus algae culture for use in food supplements can not always meet the demand for use of astaxanthin in food supplements. The use of synthetic Astaxanthindiol can also be advantageous for applications that require a concentrated, standardized Astaxanthinquelle. Conventional sources for racemic, synthetic astaxanthin are used as the dye in the salmonid aquaculture as a feed component. This racemic mixture may be of limited use, since only a quarter of the compound in the 3S, 3'S isomer form, which is commonly found in natural salmon and was tested for efficacy and safety in humans.
• Astaxanthin can also be synthesized stereospecifically, so that the result of the generally accepted 3S, 3'S isomer is exclusively in a free diol form. The free Diolkristalle can be suspended in a vegetable oil or a solid beads to be used in food preparations or in pill, capsule, tablet form. The 3S, 3'S product has the advantage of greater consistency and a lower odor than the seaweed preparation. Therefore, the product derived from seaweed astaxanthin 3'S Astaxanthindiol be replaced in existing formulations of the same or a higher efficiency by the synthetic 3S.
• Surprisingly, it was also found that the use of hyaluronic acid alone and / or in combination with astaxanthin is advantageous and synergistic. For example, patients can be low molecular weight hyaluronic acid in its various forms in an amount of 1-500 mg per day, and preferably about 10-70 mg per day, and in another example, 20-60 mg, 25-50 mg, 35 mg and 45 mg are given. Astaxanthin can be added in one example at about 2-4 mg, but could be in the range 0.5 to 4 mg daily and lie in another example, in a 7-12 mg range or from 0.5 to 12 mg , The hyaluronic acid may be added in the form of pro-inflammatory Natriumhyaluronatfragmenten low molecular weight that are difficult to about 0.5-300 kDa, corresponding to pro-inflammatory fragments of low molecular weight. Although the use of astaxanthin and phospholipids, such as, for example, krill oil, algae oil, roe, fish oil product or from plants produced oils aids in the delivery of the hyaluronic acid, the hyaluronic acid having low molecular weight and preferably in the form of the fragments is still small enough to through the intestine to be absorbed and used in an oral administration.
• It is also advantageous to use astaxanthin with the hyaluronic acid with low molecular weight. Various amounts are used and in one example, 2-4 mg per day, and in another example 0.5-12 mg daily with hyaluronic acid with a low molecular weight, such as the amount of 1-500 mg and advantageously about 10- 70 mg and are used with 0.5-12 mg or 4-12 mg astaxanthin. About 40 to 120 mg of hyaluronic acid with a low molecular weight can be used in an example. A dosage of astaxanthin may be about 6-8 mg, and hyaluronic acid with a low molecular weight may be in the range of about 60-80 mg. Although larger amounts can be used of astaxanthin with hyaluronic acid with a low molecular weight alone, it is possible to 2 mg astaxanthin and smaller amounts of hyaluronic acid having low molecular weight, such as 20 mg and up to 40 mg, to be used as a non-restrictive example. It should be understood that hyaluronic acid fragments, such as the inflammatory Natriumhyaluronatfragmente are potent low molecular weight, as Zellrezeptorsignalgebungsmolküle the innate immune system, which are associated with the inflammatory cascade, and oral hyaluronic acid in the form of fragments may reach joints with a low molecular weight, compared with the hyaluronic acid with higher molecular weight, which is injected, since it is not administered orally.
• Many modifications and other embodiments of the invention will occur to those skilled in the sense the present of the benefit of the teachings in the above description and in the accompanying drawings. It is therefore understood that the invention is not limited to the specific embodiments disclosed and that modifications and embodiments are intended to be included within the scope of the dependent claims.
• QUOTES INCLUDED IN THE DESCRIPTION
• This list of references cited by the applicant is generated automatically and is included solely to inform the reader. The list is not part of the German patent or utility model application. The DPMA is not liable for any errors or omissions.
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Claims (16)

1. Dietary supplement composition formulated in an amount effective to promote the maintenance of cardiovascular health comprising astaxanthin and a mixture of a phospholipidreichen roe extract and a seed oil extract comprising a ratio of alpha-linolenic acid (ALA) to linoleic acid (LA) is between 1: 1 and 6: 1.
2. Dietary supplement composition according to claim 1, wherein the phospholipid roe extract comprises at least 50 percent phospholipids.
3. Dietary supplement composition according to claim 1, wherein the composition is formulated to treat oxidation of low density lipoprotein (LDL) in humans.
4. Dietary supplement composition according to claim 1 and further comprising a diluent in pharmaceutical grade or food grade.
5. Dietary supplement composition according to claim 1, further comprising a phospholipid that comprises at least one selected from phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine.
6. Dietary supplement composition according to claim 1, further comprising a phospholipid derived from at least one from a vegetable source, a seaweed source and an animal source or a synthetic derivative.
7. Dietary supplement composition according to claim 1, wherein the composition contains 0.5 to 12 mg astaxanthin.
8. Dietary supplement composition according to claim 1, wherein the composition contains 50 to 500 mg of phospholipidreichen roe extract.
9. Dietary supplement composition according to claim 1, wherein the dietary supplement composition is formulated in a single dose capsule.
10. Dietary supplement composition according to claim 1, wherein the astaxanthin is derived from a synthetic or natural ester or diol.
11. Dietary supplement composition according to claim 1, wherein the astaxanthin makes up about 0.1 to 15 weight percent of the mixture of phospholipidreichem roe extract and seed oil extract.
12. Dietary supplement composition formulated in an amount effective to treat the oxidation of low density lipoprotein (LDL) in humans, comprising astaxanthin derived from a synthetic or natural ester or diol, and a mixture of a phospholipidreichen roe extract and a seed oil extract comprising a ratio of alpha-linolenic acid (ALA) to linoleic acid (LA) is between 1: 1 and 6: 1 and formulated in a single dose capsule, wherein the astaxanthin makes up about 0.1 to 15 weight percent of the mixture of phospholipidreichem roe extract and seed oil extract.
13. Dietary supplement composition according to claim 12, wherein the phospholipid roe extract comprises at least 50 percent phospholipids.
14. Dietary supplement composition according to claim 12 and further comprising a diluent in pharmaceutical grade or food grade.
15. Dietary supplement composition according to claim 12, wherein the composition contains 0.5 to 12 mg astaxanthin.
16. Dietary supplement composition according to claim 12, wherein the composition contains 50 to 500 mg of phospholipidreichen roe extract.