CN1323544A - Compositions and methods for lowering low-density lipoprotein cholesterol concentrations - Google Patents
Compositions and methods for lowering low-density lipoprotein cholesterol concentrations Download PDFInfo
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- CN1323544A CN1323544A CN00120362A CN00120362A CN1323544A CN 1323544 A CN1323544 A CN 1323544A CN 00120362 A CN00120362 A CN 00120362A CN 00120362 A CN00120362 A CN 00120362A CN 1323544 A CN1323544 A CN 1323544A
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Abstract
The present invention relates to a composition comprising phytosterols and soy protein material and/or isoflavones selected from the group consisting of genistein, daidzein, glycitein, biochanin A, formononetin and their respective naturally occurring glycosides, wherein the phytosterols comprise at least 0.49% by weight of the composition. The invention also relates to a method of lowering the concentration of LDL and total cholesterol in human blood which comprises co-administering to a human a phytosterol and a soy protein material and/or an isoflavone, said phytosterol comprising at least 0.49% by weight of the combined weight of phytosterol and soy protein material and/or isoflavone. The present invention also relates to a method of preventing or slowing the progression of atherosclerosis in a human which comprises co-administering to the human phytosterols and soy protein material and/or isoflavones, said phytosterols comprising at least 0.49% by weight of the combined weight of the phytosterols and soy protein material and/or isoflavones.
Description
The present invention relates to reduce the method and composition of concentration of low density lipoprotein cholesterol and total cholesterol concentration in the blood.Specifically, the present invention relates to contain plant sterol, soybean protein and osajin, and the compositions of their mixture, said composition is used to reduce the concentration of blood LDL-cholesterol and T-CHOL, and it is atherosis and slow down development of atherosclerosis to be used for prevention of arterial.
The sickness rate height of cardiovascular disease, the mortality rate that causes is also high, and is especially true in the U.S. and the Western European countries.Several causes that relate to cardiovascular disease development comprise and heritability, sex, life style factor (for example smoking and diet), age, hypertension and the hyperlipemia of disease comprise hypercholesterolemia.Several in these factors, especially hyperlipemia and hypercholesterolemia play effect to development of atherosclerosis, are blood vessel and cardiopathic main cause.
High blood cholesterol concentration is one of main hazard factor of human angiopathy and coronary heart disease.High low-density lipoprotein cholesterol (hereinafter claiming " LDL-cholesterol ") and high T-CHOL increase directly related with the danger of coronary heart disease.Anderson, Castelli ， ﹠amp were followed the tracks of in cholesterol and mortality rate: Framinghan research 30 years; Levy, JAMA, Vol257, pp.2176-80 (1987).
The soybean protein of taking in the diet is relevant with the reduction of the danger of coronary heart disease, and this is reflected in the reduction of serum cholesterol level.Known soybean protein reduces T-CHOL and the LDL-cholesterol levels in the animal blood.Absorption about soybean protein is obviously relevant with the reduction of human serum T-CHOL and LDL-cholesterol concentration to the metabolic analysis demonstration diet soybean protein of the influence of lipid in the human serum recently.The absorption of soybean protein is to the metabolic analysis of fat shield influence in the human serum, Anderson, Johnstone, and Cook-Newell, " New England Journal of Medicine " (N.Eng.J.Med.), the 333rd volume, the 5th phase, 276-82 page or leaf (1995).
It is reported that the absorption of chemical compound-plant sterol of finding in the full Semen sojae atricolor reduces circulation T-CHOL and LDL cholesterol levels in the blood.Diet plant sterol: the summary of metabolism, benefit and side effect, Ling﹠amp; Jones, " life sciences " (Life Sci.), Vol.57:3, pp.195-206 (1995).Plant sterol is the sterol compound that plant produces, and they are structurally very similar with cholesterol, and different is, and they are general all at the C of sterol side chain
24Bit strip has some substituent groups.Common plant sterol comprises unsaturated sterol B-sitosterol, campesterol and stigmasterol (as shown in Figure 1) and their saturated homologue sitostamol (sitostanol) and campestanol (campestanol) (as shown in Figure 2).The diet source of plant sterol is Semen Maydis oil, soybean oil and other plant oil, and they contain hydrophobic relatively chemical compound.
Phytoestrogen isoflavone shown in the accompanying drawing 3 and 4 is the another kind of chemical compound of finding in full Semen sojae atricolor, thinks that recently they are to make the principal element that LDL and total cholesterol concentration reduce in the blood.Purification spissated isoflavone, especially genistein can suppress the biosynthesis of cholesterol and stop the oxidation of LDL cholesterol, and this oxidation step is an important step in the progression of atherosclerosis.Referring to, Korean Patent 97-20103 for example; The activation of the phosphatidase D of the low density lipoprotein, LDL of oxidation mediation in smooth muscle cell: in cell proliferation and atheroma form, may act on Natarajan etc., J.Lipid Res., 36:9, pp.2005-16 (nineteen ninety-five JIUYUE).
Produce in the conventional process of soybean oil, soybean protein and medicine or food additives composition the full Semen sojae atricolor of processing, plant sterol, isoflavone and soybean protein are separated.Adopt machinery and chemical method to extract peeled soybeans, plant sterol is separated with isoflavone with soybean protein, enter the soybean oil part, this part contains fat and liposoluble substance.With soybean oil part with remaining soybean materials---" defatted soybean material " separates and is used for Oleum Glycines and vegetable oil, also can further be processed into shortening, margarine and lecithin.
The defatted soybean material claims defatted soybean cake usually, is used as to produce the raw material that contains a large amount of soy protein products, for example produces soybean protein concentrate and soy protein isolate.The defatted soybean material that is used to produce soy protein products also contains isoflavone.Yet, producing soy protein material, for example in the conventional method of soybean protein concentrate and soy protein isolate, a large amount of isoflavone are but by separating from the soybean protein material with alcohol extract or aqueous extract washing soya bean albumen material.Referring to, for example soy protein products, characteristic, nutrition and utilization, pp.3-6 (Pub.Soy Protein Council, 1987).
In the suitability for industrialized production of soy protein material, people's attention is to separate isoflavone from soy protein material, because when having isoflavone in the soy protein material, is considered to and relatively poor flavour, and abnormal smells from the patient and/or color are relevant.For example United States Patent (USP) 5804234 has been instructed and has a kind ofly been removed isoflavone by protein substance is contacted with adsorbent resin from soybean materials, thereby produces the method for the preferable soy protein material of local flavor.Especially preferably soy protein material is carried out alcohol extraction,, can very from soy protein material, remove isoflavone effectively in part because of alcohol because alcohol extraction is better than the flavour of the vegetable protein thing of water extraction generation.Referring to, Japan Patent 63-245648A for example.
Recently, people's attention also concentrates on from vegetable material, especially separates the isoflavone that wherein exists in Semen sojae atricolor, the Semen astragali sinici, so that the refining isoflavone material that can be used for keeping healthy to be provided.For example, following patent disclosure various methods of from vegetable material, separating isoflavone: United States Patent (USP) 4428876; 5702752; 5679806; 4390559; 4366248; 4366082; 4264509; 4232122; 4157984; Japan Patent 1-258669A; 5-170756A; 41-90720A; 62-126186A; With PCT patent application WO93/23069.Isolated isoflavone compounds can be used for pharmaceutical composition or food additives composition, to prevent or to treat various bad health status, comprises the reduction elevated cholesterol.For example, isolated isoflavone material can be used for medicine or food additives composition, described in following patent documentation: United States Patent (USP) 5516528; 5424331; 5569459; 5654011 and PCT patent application WO93/23069.
Still need obviously to reduce LDL and total cholesterol level in the blood, thereby the danger that obviously reduces atherosclerosis and coronary heart disease is all utilized the new method and the compositions of soybean component.
On the one hand, the present invention is a kind of compositions that contains soy protein material, at least a isoflavone and a plant sterols, described soy protein material contains the soybean protein that accounts for soy protein material dry weight 49% at least, described isoflavone is selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring separately glucosides and glucosides conjugate, and wherein plant sterol accounts for 0.49% of composition weight at least.
On the other hand, the present invention is a kind of compositions that contains soy protein material and plant sterol, and described soy protein material contains and accounts for soy protein material at least in heavy 49% soybean protein, and plant sterol wherein accounts for 0.49% of composition weight at least.
On the other hand, the present invention is a kind of compositions that contains an at least a isoflavone and a plant sterols, described isoflavone is selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring separately glucosides and glucosides conjugate, and wherein plant sterol accounts for 0.49% of composition weight at least.
On the other hand, the present invention is a kind of method that reduces the concentration of LDL and T-CHOL in the human blood, this method comprises uniting to the people takes soy protein material, isoflavone and plant sterol, described soy protein material contains the soybean protein that accounts for soy protein material dry weight 49% at least, described isoflavone is selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring separately glucosides and glucosides conjugate, with the LDL in the reduction human blood and the concentration of T-CHOL.Uniting the plant sterol of taking accounts at least and unites 0.49% of soy protein material, isoflavone and the plant sterol gross weight of taking.In preferred scheme, unite to the people and to take plant sterol, soy protein material and isoflavone, to prevent human atherosclerosis and to slow down development of atherosclerosis.
On the other hand, the present invention is a kind of method that reduces the concentration of low-density lipoprotein cholesterol and T-CHOL in the human blood, this method comprises uniting to the people takes soy protein material and plant sterol, described soy protein material contains the soybean protein that accounts for soy protein material dry weight 49% at least, with the LDL in the reduction human blood and the concentration of T-CHOL.Uniting the plant sterol of taking accounts at least and unites 0.49% of the soy protein material taken and plant sterol gross weight.In preferred scheme, unite to the people and to take plant sterol and soy protein material, to prevent human atherosclerosis and to slow down development of atherosclerosis.
On the other hand, the present invention is a kind of method that reduces the concentration of LDL and T-CHOL in the human blood, this method comprises uniting to the people takes plant sterol and isoflavone, described isoflavone is selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring separately glucosides and glucosides conjugate, with the LDL in the reduction human blood and the concentration of T-CHOL.Unite the plant sterol of taking and account for 0.49% of the gross weight of uniting the plant sterol taken and isoflavone at least.In preferred scheme, unite to the people and to take plant sterol and isoflavone, to prevent human atherosclerosis and to slow down development of atherosclerosis.
On the other hand, the present invention is a kind of compositions that contains soybean hypocotyl material and plant sterol, and plant sterol wherein accounts for 0.49% of composition weight at least.
Accompanying drawing 1 has been described the molecular structure of unsaturated plant sterol cupreol, campesterol and stigmasterol.
Accompanying drawing 2 has been described the molecular structure of saturated plant sterol sitostamol and campestanol.
Accompanying drawing 3 has been described the molecular structure of the Aglucone isoflavone that uses among the present invention.
Accompanying drawing 4 has been described the molecular structure of representative isoflavone glucoside and isoflavone glucoside conjugate.
" Mal " expression " malonyl " that this paper adopts, " Ac " expression " acetyl group ". Term " subtracts Slow " or its derivative comprise and suppress wholly or in part specific biological agent (about using that term slows down Literary composition can be expressly understood). When being defined as, " isoflavones " or " phytoestrogen " be selected from one group of isoflavones At least a the time, term " isoflavones " or " phytoestrogen " that this paper adopts can be understood as a kind of Isoflavones or phytoestrogen, perhaps multiple isoflavones or phytoestrogen. Term " isoflavone glucoside " is Refer to have the isoflavones of the sugar monomer covalently bound with it. Term " isoflavone glucoside conjugate " refers to have Another molecule residue that is connected with the sugar moieties of isoflavone glucoside such as the isoflavone glucoside of ester. This paper adopts " pharmaceutical preparation " is by the mixture of a kind of compound of physician's prescription or multiple compounds and effectively releases to the people Put the mixture of excipient of the mixture of described compound or compound. The OTC preparation is with effective to the people The mixture of one or more compounds of the excipient combination of release compound or compound mixture, they Need not physician's prescription can take to the people.
The present invention is based on following discovery finishes: when the effective dose connection that reduces cholesterol to unite each composition of taking Close when taking phytosterol and soy protein material and/or isoflavones, can work in coordination with and reduce low-density in the human blood The level of lipoprotein cholesterol and T-CHOL. Therefore, the present invention relates to the use in conjunction phytosterol (also claims Be " phytosterols ") reduce LDL and total in the blood with soy protein material and/or selected isoflavones The composition of cholesterol concentration and method. In addition, phytosterol and soy protein material, and especially with The isoflavones use in conjunction by reducing LDL and T-CHOL in the blood concentration and by anti-oxidant action and The next effective prevention of arterial of tyrosine kinase inhibitory activity is atherosis or slow down atherosclerotic development. Cause This, it is atherosis or slow down composition and the side of atherosclerotic development to the invention still further relates to prevention of arterial Method. Composition
In a scheme, composition of the present invention comprises phytosterol and the soy protein material of use in conjunction Or at least a isoflavones, described soy protein material contains and accounts at least 49% of soy protein material dry weight, Described isoflavones be selected from genistein, daidzein, Glycitein, Biochanin A, onocerin and They are naturally occurring glucosides and glucosides conjugate separately; Perhaps the phytosterol of use in conjunction, isoflavones and Soy protein material. Most preferred composition contains all three kinds of compositions: phytosterol, soy protein material And isoflavones, therefore, can work in coordination with the LDL and the T-CHOL reduction effect that utilize each composition.
In another scheme, composition of the present invention comprises the plant with soybean hypocotyl material use in conjunction Sterol, the soybean hypocotyl material generally contains the soybean protein of the 37%-that has an appointment about 44% (weight). Under the soybean Plumular axis/phytosterol compositions also can comprise at least a genistein, daidzein, the Huang of being selected from addition Beans flavine, Biochanin A, onocerin and they are naturally occurring glucosides and glucosides conjugate different separately Flavones.
Phytosterol
The phytosterol that can be used for the present composition comprises saturated and undersaturated phytosterol. Can be used for this The preferred unsaturated phytosterol of invention composition is the cupreol shown in the accompanying drawing 1, campesterol and beans The oil sterol. The preferred Phytostanol that can be used for the present composition is the rape oil gonane shown in the accompanying drawing 2 Pure and mild soya-bean oil stanols. Undersaturated sterol cupreol and campesterol are particularly preferred.
The amount of the phytosterol in the present composition is at least 0.49% of composition gross weight, more preferably group About 0.5%-of compound gross weight is about 99.5%, most preferably is about 1%-about 60% of composition gross weight. Combination The relative quantity of phytosterol depends on whether said composition contains soy protein material in the thing. If composition contains Soy protein material is arranged, and the amount of phytosterol is starkly lower than the not group of soybean protein-containing material usually in the composition Phytosterol amount in the compound (to account for the percentage of composition gross weight).
Soy protein material
In a scheme, the soy protein material that can be used for the present composition is the soy protein material that contains the soybean protein that accounts for soy protein material dry weight 49% at least.At least the preferred soy protein material that contains 49% soybean protein (dry weight) is defatted soybean flour and Semen sojae atricolor sheet, and they contain 49%～about 65% (weight) soybean protein; The soybean protein concentrate, they contain 65%～about 90% (weight) soybean protein at least; And soy protein isolate, they contain the soybean protein of 90% (weight) at least.Soybean protein concentrate and soy protein isolate are particularly preferred.In another scheme, the soy protein material that can be used in the present composition is the soybean hypocotyl material.
The amount of the soy protein material that exists in the present composition accounts for 0%～99.55% of compositions gross weight.When comprising soy protein material in the said composition, it preferably accounts for the major part of compositions gross weight at least, be more preferably about 55%～about 99.55% of compositions gross weight, especially preferably the compositions gross weight is about 75%～and about 99.55%, most preferably be about 80%～about 99.5% of compositions gross weight.If isoflavone-containing not in the compositions then always contains soy protein material.
Isoflavone
The isoflavone that can be used in the present composition is the glucosides and the glucosides conjugate of Aglucone isoflavone genistein, daidzein, Glycitein, biochanin A, formononetin and naturally occurring these Aglucone isoflavones shown in the accompanying drawing 3, comprises the genistin shown in the accompanying drawing 4,6 "-O-Mal genistin, 6 "-O-Ac genistin, daidzin, 6 "-O-Mal daidzin, 6 "-O-Ac daidzin, glycitin and 6 "-O-Mal glycitin.Can use one or more isoflavone in the compositions.Aglucone isoflavone is particularly preferred, because they are the strongest isoflavone of biological activity.The most preferably isoflavone that is used for the present composition is genistein, daidzein, biochanin A and/or formononetin.
The amount of isoflavone accounts for 0% of compositions gross weight～about 60% in the compositions.When comprising soy protein material in the compositions, the amount of isoflavone accounts for about 0%～about 15% of compositions gross weight in the compositions.Isoflavone levels most preferably accounts for about 0.0066%～about 10% of compositions gross weight.If compositions is the soybean protein-containing material not, then always contain isoflavone.
Compositions of the present invention can adopt method well known in the art and step to prepare by obtaining and mixing mentioned component.
Plant sterol can obtain by extraction and separating plant sterol from plant or by the synthetic sterol of chemical means.Perhaps, can use the oil that contains plant sterol with the amount of the plant sterol that is enough to provide desired level in compositions in the compositions, described oil is to extract from the plant that contains plant sterol with the conventional method of extraction vegetable oil.
In a preferred scheme, plant sterol is that the method according to United States Patent (USP) 3993756 (particularly embodiment 10) obtains from nonsaponifying soybean oil fraction, and the document is incorporated by reference in this article.Briefly, be from full Semen sojae atricolor, to obtain the nonsaponifying soybean oil fraction that contains the 40-50% that has an appointment (weight) plant sterol.Soybean oil adopts conventional pulverizing, remove the peel, peel off and extracting method obtains from full Semen sojae atricolor.Soybean oil is made with extra care by the soybean oil process for purification until last deodorize step of routine.The deodorize of soybean oil is carried out in 225 ℃～235 ℃ under 2-3mmHg decompression, with distillation from soybean oil with separate the extract that contains plant sterol.By (weight ratio: 1 gram extract: 1.72 gram methanol, 0.019 gram sulphuric acid) free fatty that contained in extract at 65-70 ℃ of backflow 3-4 hour is converted into methyl ester with extract and methanol and concentrated acid.Behind the stopped reaction, methanol is removed in decompression, and sulphuric acid is removed in 80-100 ℃ water washing of residual grease.Then by remove the methyl ester of fatty acid in 170-190 ℃ of distillation at 20-30mm Hg.The residue of purification gained obtains containing the nonsaponifying soybean oil fraction of 40-50% plant sterol.The plant sterol in the sponifiable fraction is not cupreol, campesterol and stigmasterol.The sponifiable fraction can further not pass through the HPLC purification, obtains each plant sterol monomer, perhaps more preferably will be not the sponifiable fraction directly as the source of the plant sterol of the present composition.
Cupreol also can extract from other plant oil according to known method.The methods of (J.Am.Chem.Soc.) describing in 48,2897 (1926) in " JACS " according to Anderson etc. can be separated cupreol from wheat germ oil and Semen Maydis oil; According to the methods that Gloyer etc. (J.Am.Chem.Soc.) describes in 61,1901 (1939) in " JACS ", can from the rye (Secale cereale L.) germ oil, separate cupreol; Wallis at " organic chemistry magazine " (J.Org.Chem.), the methods of describing in 2,335 (1937) can be separated cupreol from Oleum Gossypii semen; And according to Sandqvist etc. at Ber.64, the methods of describing in 2167 (1931) can be extracted cupreol from tall oil, these documents are all incorporated by reference in this article.
Campesterol also can extract from other value thing oil at the known method that provides in " JACS " 63,1155 (1941) according to for example Fernholz etc., and the document is incorporated by reference in this article.Campesterol also can be by Tarzia etc. at Gazz.Chim.Ital., and 97,102 (1967) and " chemical abstracts " (Chem Abstr.), 67, the method for describing among the 32883q is synthetic, and these two pieces of documents are incorporated by reference in this article.Stigmasterol can separate from Semen sojae atricolor or calabar bean.
Saturated plant sterol can obtain by hydrogenation from their unsaturated homologue.Utilize conventional method for hydrogenation, cupreol and stigmasterol can be converted into sitostamol, campesterol is converted into campestanol.
Some plant sterols have commodity selling, can directly mix in the compositions of the present invention after buying.For example, campesterol and stigmasterol can be from Aldrich Chemical Company, Inc.940 West SaintPaul Avenue, Milwaukee, Wisconisin buys, and cupreol can be from Sigma ChemicalCompany, 3050 Spruce Street, St.Louis, Missouri buys.
In a scheme, soy protein material is defatted soybean protein powder or particle, soybean protein concentrate or soy protein isolate, and they respectively contain the soybean protein of at least 49% (weight).For obtaining defatted soybean flour or Semen sojae atricolor particle, according to the soybean processing method of routine, with full Semen sojae atricolor clean, pulverizing, peeling and defat to be to produce soybean flakes, Semen sojae atricolor sheet, Semen sojae atricolor powder or the soybean cake of defat, produces Semen sojae atricolor powder and Semen sojae atricolor particle thus.Defatted soy flakes and Semen sojae atricolor powder also have commercially available.Defatted soybean flour and defatted soybean particle can be made by pulverizing by defatted soy flakes, Semen sojae atricolor sheet, Semen sojae atricolor powder or soybean cake according to conventional method.Defatted soybean flour is pulverized to particle diameter is 150 μ or littler granule (being enough to make granule to pass through the U.S.'s 100 mesh sieves), the defatted soybean particle is pulverized the granule (being enough to make granule to pass through U.S. 10-80 mesh sieve) to about 2000 μ for particle diameter 150 μ.Defatted soybean flour and defatted soybean particle contain 49% (weight) soybean protein to about 65% (weight) soybean protein, and all the other compositions of Semen sojae atricolor powder and Semen sojae atricolor particle mainly comprise sugar, soybean fiber and ash.Defatted soybean flour and Semen sojae atricolor particle have commercially available, can directly mix in the compositions of the present invention after buying.
The preferred soy protein material that is used for the present composition is soybean protein concentrate or soy protein isolate, and the soybean protein amount that they contain is apparently higher than Semen sojae atricolor powder or Semen sojae atricolor particle.The soybean protein concentrate contains about 65% soybean protein to about 90% (weight), and all the other compositions of soybean protein concentrate mainly comprise soybean fiber and other polysaccharide.The soybean protein concentrate that is used for the present composition can be made with the conventional method of producing the Semen sojae atricolor concentrate, and conventional method comprises that (ⅰ) uses aqueous alcohol, preferably aquiferous ethanol or methanol wash defatted soy flakes or Semen sojae atricolor powder; (ⅱ) thin or Semen sojae atricolor powder with the weak acid scrubbing defatted soybean sheet that has soy protein isoelectric point pH (pH4.4-4.6) approximately; Or (ⅲ) Steam Heating defatted soy flakes or Semen sojae atricolor powder make albuminous degeneration, wash soybean flakes or Semen sojae atricolor powder then with water.The soybean protein concentrate has commercially available, can directly mix in the compositions of the present invention after buying.
The most preferably soy protein material that is used for the present composition is soy protein isolate (being also referred to as soy protein isolate), and in the soy protein material of processing, the soybean protein content in the soy protein isolate is the highest.Soy protein isolate contains at least 90% (weight) soybean protein, and all the other compositions in the soy protein isolate mainly comprise ash and moisture.The soy protein isolate that is used for the present composition can make with the conventional method that forms soy protein isolate, this method is for being about 6 to about 11 aqueous solution with pH, preferred dilute sodium hydroxide, calcium hydroxide or Ammonia extract defatted soy flakes, and will contain the extract and the insoluble substance of soluble protein, for example soybean fiber separates with other insoluble polysaccharide.The pH of isolating extracting solution is transferred to the isoelectric point, IP of about soybean protein, and preferably about pH4.4-4.6 is with protein precipitation.The albumen of precipitation separation from the liquid part of extract is so that albumen separates with soluble sugar.Wash isolating albumen then, also it can be neutralized, obtain soy protein isolate.Soy protein isolate has commercially available, can directly mix in the compositions of the present invention after buying.
In another scheme, soy protein material is the soybean hypocotyl material, and it contains the soybean protein of the 37%-that has an appointment about 44% (weight).For obtaining the soybean hypocotyl material,,, cut soybean cotyledon according to conventional soybean processing technology with full defilming soybean.Cotyledon cuts the back hypocotyl to be separated, and can be enough to selectivity and removes the sieve in the aperture of little hypocotyl and sieve and separate with having by the Semen sojae atricolor that will cut.Rough plumular axis can be pulverized or be pulverized or face.
The isoflavone that uses in the present composition is naturally occurring material, and they can be found in plant, for example in beans, Herba Trifolii Pratentis and the Radix Puerariae.The common beans source of these isoflavone comprises the Semen sojae atricolor and the Semen Pisi sativi of Semen sojae atricolor, Cicer arietinum Linn. and various other kinds.The Herba Trifolii Pratentis source of these isoflavone compounds comprises red Herba Trifolii Pratentis and underground Herba Trifolii Pratentis.Semen sojae atricolor is particularly preferred isoflavone compounds source (only not having biochanin A and its glycoside in the Semen sojae atricolor).
Isoflavone compounds can obtain from the natural plant origin of isoflavone that exists, and some isoflavone compounds can make by methods known in the art are synthetic.Daidzein method (the Chem.﹠amp that can from red Herba Trifolii Pratentis, separate or can provide according to Ganguly and Sarre according to Wong disclosed method (J.Sci.Food Agr., Vol.13, p.304 (1962)) for example; Ind. (London), p.201 (1970)) from mycete Micromonospora halophytica, separate, these two pieces of documents are all incorporated by reference in this article.Daidzein can prepare by following known method is synthetic: (J.Chem.Soc. such as Baker, p.274 (1933)), Wesley etc. (Ber.Vol.66, p.685 (1933)), (J.Chem.Soc. such as Mahal, p.1769 (1934)), Baker etc. (J.Chem.Soc., p.1852 (1953)), or Farkas (Ber.Vol.90, p.2940 (1957)), these documents are all incorporated by reference at this paper.The isoflavone aglycone daidzin can be by the synthetic preparation of the method (Ber.Bol.92, p.819 (1959)) of Farkas etc., and the document is incorporated by reference at this paper.Daidzein isoflavone aglycone conjugate 6 '-O-Mal daidzin and 6 '-O-Ac daidzin can make with the conventional saponification of malonic anhydride and acetic anhydride respectively by daidzin.
Genistein can be by the synthetic preparation of following literature method: Baker etc. (J.Chem.Soc., p.3115 (1928)); Narasimhachari etc. (J.Sci.Ind.Res., Vol.12, P.287 (1953)); Yoder etc. (Proc.IowaAcad.Sci., Vol.61, p.271 (1954)); With (Acta.Chim.Acad.Sci.Hung., Vol.19, p.277 (1959)) such as Zemplen, these documents are all incorporated by reference at this paper.The isoflavone aglycone genistin can be by the synthetic preparation of the method (Ber., Vol.76B, p.1110 (1943)) of Zemplen etc., and the document is incorporated by reference at this paper.Isoflavone conjugate 6 '-O-Mal genistin of genistin, 6 '-O-Ac genistin can make with the conventional saponification of malonic anhydride and acetic anhydride respectively by genistin.
Biochanin A can be by the synthetic preparation of the method (Nature169:706 (1952)) of Baker etc., and the document is incorporated by reference at this paper.Biochanin A also can be from red Herba Trifolii Pratentis by method (the Chem. ﹠amp of Pope etc.; Ind. (London) p.1092 (1953)) separate, the document is incorporated by reference at this paper.Formononetin can be by the synthetic preparation of (TetrahedronLetters, p.593 (1962)) disclosed methods such as Wessely etc. (Ber.66:685 (1933)) and Kagel, and these two pieces of documents are incorporated by reference at this paper.Formononetin also can separate or can be from Trifolium separate by the method (J.Chem.Soc., p.3447 (1951)) of Bradbury etc. from the method (Ann.489:118 (1931)) of Semen sojae atricolor powder by Walz, and these two pieces of documents are all incorporated by reference at this paper.
In most preferred scheme, the isoflavone component of the present composition is to reclaim to obtain from the soy protein material that can be used for the present composition.As mentioned above, isoflavone is the natural chemical compound that is present in the Semen sojae atricolor.In the production of soybean protein powder, coarse powder, concentrate and separator, still remain with some isoflavone in the soy protein material.As when above-mentioned soybean processing protein substance produces soybean protein powder, coarse powder, concentrate or separator, utilize suitable process technology will obviously increase isoflavone amount in the soy protein material (comparing) with the isoflavone amount in the soy protein material of routine processing.Particularly should avoid with alcohol washing and extracting soybean protein concentrate, because the isoflavone height is dissolved in the aqueous alcohol, if keep isoflavone in soy protein material, the soybean protein concentrate is not used the alcohol washing yet and is produced.In addition, the operation of washing soy protein material also should reduce to minimum, because washing meeting flush away isoflavone from soybean protein.If wash, also should carry out (0 ℃-45 ℃) at a lower temperature, so that the insoluble maximum of isoflavone in water washing liquor, thereby reduce the isoflavone loss that is in the suds.Isoflavone in the soy protein material should be as according to following its aglucon form that is converted into, so as wash with water or the extracting soybean protein substance before reduce the dissolubility of isoflavone in water.Use said method to help to make isoflavone to be retained in the soy protein material, thereby make the soy protein material that obtains contain the isoflavone of significant quantity.
In another scheme, can from the natural plant material that has an isoflavone, separate one or more isoflavone, be used for compositions of the present invention.The method for optimizing that separates isoflavone compounds from the natural plant material that has an isoflavone is that particular methanol or ethanol are perhaps used aqueous solution with alcohol, and preferred bases aqueous solution extraction plant material is to extract isoflavone from plant material.Preferably before the extraction isoflavone compounds, pulverize plant material, from plant material, to reclaim isoflavone compounds to greatest extent.Can pass through conventional separation method, for example reversed-phase high pressure liquid chromatography (" HPLC ") is separated isoflavone compounds from extract.
In a preferred version, isoflavone compounds genistein, genistin, 6 '-O-Mal genistin, 6 '-O-Ac genistin, daidzein, daidzin, 6 '-O-Mal daidzin, 6 '-O-Ac daidzin, Glycitein, glycitin and 6 '-O-Mal glycitin can separate in the preferred commercially available soybean material from soybean material.The soybean material that can therefrom separate isoflavone compounds comprises: Semen sojae atricolor, peeled soybeans, Semen sojae atricolor powder, big bean flour, Semen sojae atricolor particle, soybean flakes (full-cream and defat), soybean cotyledon, soybean hypocotyl, soy molasses, soybean protein concentrate, soy-bean whey, soybean whey protein and soy protein isolate.In a scheme; use the low-molecular-weight organic extractant; preferred alcohols, ethyl acetate, acetone or ether; more preferably ethanol or methanol in water extract isoflavone from Semen sojae atricolor, peeled soybeans, Semen sojae atricolor powder, big bean flour, Semen sojae atricolor particle, soybean flakes, soybean protein concentrate, soybean whey protein or soy protein isolate in preferred Semen sojae atricolor powder, big bean flour, Semen sojae atricolor particle or the soybean flakes.Most preferred extractant has the pH value (about pH4-pH5) that is about soy protein isoelectric point, with the amount of the soybean protein that reduces the extractant extraction.
The extractant that will contain isoflavone separates the extract that isoflavone is rich in formation with insoluble soybean material.If desired, can be rich in the material of isoflavone by removing the concentrated extract recovery of desolvating, thereby obtain the solid-state material that is rich in isoflavone, this material can be used in the compositions and methods of the invention.
In a preferred scheme, can be further with other soluble soybean separating substances purification in isoflavone compounds and the extract.The extract of isoflavone-containing is contacted the isoflavone that is adsorbed with the solvent that isoflavone is eluted from adsorbing material specifically eluting from the adsorbing material with the material of isoflavone in the sorption extraction thing.
In a preferred scheme, separate by conventional reversed-phase HPLC isoflavone is separated with impurity in the extract.From soybean material the extraction isoflavone and with extract with after insoluble soybean material separates, extract is filtered to remove the insoluble substance that may stop up the HPLC post.Fill conventional commercially available HPLC post with specific adsorbent and prepare the HPLC post, this adsorbent will be with specificity mode desorption ground in conjunction with isoflavone in the extract and impurity.Adsorbent can be any reversed-phase HPLC filler, but preferred filler is selected by load capacity, separation efficiency and cost standard.A kind of preferred packing material is available from Sweden Eka Nobel, the Kromasil C18 16un 100 dust microballons of Nobel Industries.
Make the extract after the filtration all saturated fully by isoflavone by filling HPLC post all binding sites on post, this can detect by the appearance of the isoflavone in the effluent from post.Then with this HPLC post of solvent elution to separate.In a preferred scheme, eluent is a kind of polar solvent, for example ethanol, methanol, ethyl acetate or acetonitrile, and preferably pure content is about 90% for about 30%-, 50% alcohol-water solution most preferably from about, most preferred alcohol is ethanol.
Separate collection isoflavone compounds and impurity from the post eluent.Distinguish isoflavone fraction and other eluting fractions of eluting according to conventional H PLC and analytical chemistry means.Can collect down isoflavone fraction the eluent from post, and remove volatile solvent (as, ethanol) by evaporation.If all solvents have been removed in evaporation, can directly reclaim isoflavone compounds, perhaps can be by the residual solvent of condensation (as, water) and centrifugal or isolated by filtration isoflavone and residual solvent, recovery isoflavone compounds.
In particularly preferred scheme, isoflavone aglycone conjugate and the isoflavone aglycone that reclaims can be converted into their corresponding Aglucone isoflavone forms from plant.Isoflavone aglycone conjugate and isoflavone aglycone can carry out on the substrate that therefrom can extract phytoestrogenic isoflavone to the conversion of Aglucone isoflavone, perhaps can with the extract that is rich in isoflavone after the insoluble plant raw material separates in carry out.It is believed that the Aglucone isoflavone chemical compound has special activity reducing LDL and blood total cholesterol concentration and prevention or slow down in the development of atherosclerosis.Aglucone isoflavone separates from aqueous extract with the glycosides form is easier than the conjugate of its corresponding glycosides, because aglucon is more water insoluble.
The isoflavone aglycone conjugate (as; 6 "-O-Mal genistin; 6 "-O-Ac genistin; 6 "-O Mal daidzin; 6 "-O-Ac daidzin and 6 "-O-Mal glycitin) can be by following its corresponding glycosides (as; genistin; daidzin and glycitin) that is converted into: the alkaline aqueous solution pH that forms isoflavone-containing extract or substrate is about 6-about 13; the about pH11 of preferably about pH9-; at about 2 ℃-Yue 121 ℃; preferably about 25 ℃-Yue 75 ℃ of a period of times that this alkaline aqueous solution processing is enough to transform, preferred about 30 minutes-Yue 5 hours, more preferably from about 30 minutes-Yue 1.5 hours.Isoflavone aglycone (as, genistin, daidzin and glycitin) can followingly be converted into its corresponding aglucon form (as, genistein, daidzein and Glycitein): with isoflavone aglycone and cleavable 1, the enzyme of 4-β glycosidic bond, preferred commercially available β-Pu Tangganmei, alpha-galactosidase or beta galactosidase, pectase, Lactose enzyme, glucoamylase, has active pH at enzyme, generally be in about 25 ℃-Yue 75 ℃ under the about pH9 of about pH3-, more preferably from about 45 ℃-Yue 65 ℃ contact a period of time that is enough to transform down, generally be about 1 hour-Yue 24 hours, preferred about 1 hour-Yue 3 hours.
Aglucone isoflavone can adopt conventional separation method to separate from the plant substrate.For example, available low-molecular-weight alcohol separation ligand isoflavone from Semen sojae atricolor or Herba Trifolii Pratentis substrate.Can be by conventional recrystallization method or HPLC separation ligand isoflavone from extract.In a particularly preferred scheme, from the Semen sojae atricolor substrate, separate and the isoflavone component that is used for the present composition or method comprises at least 40% genistein, at least 15% daidzein and at least 1% Glycitein.In another particularly preferred the present invention program, from the Semen sojae atricolor substrate, separate and the isoflavone component that is used for the present composition or method contains at least 85% genistein, at least 5% daidzein and at least 0.5% Glycitein.
Some isoflavone compounds that are used for the present composition have commercially available, can allocate compositions of the present invention after buying into or be used for method of the present invention.For example, genistein, daidzein and Glycitein have commercially available, and they can be available from Indofine Chemical Company Inc., P.0.Box473, and Somerville, New Jersey08876.Biochanin A can be available from Aldrich ChemicalCompany, Inc., 940 West Saint Paul Avenue, Milwaukee, Wisconsin53233.
Plant sterol and soy protein material and/or isoflavone can be added in the compositions of the present invention together, preferably they are fully mixed.For example, plant sterol and soy protein material and/or isoflavone are put into the cutting tube or mixing drum mixing time enough fully mixes them.
Preferably each composition is mixed the various compositions that the compositions that obtains contains the biological activity amount, but be not limited to contain the various compositions of biological activity amount in the compositions, because, can repeatedly take compositions of the present invention for obtaining to reduce the required effect of blood LDL and total cholesterol concentration.Compositions preferably contains the 500 milligrams-Yue 50 gram plant sterols of having an appointment, and more preferably contains 1 Ke that has an appointment-Yue 10 gram plant sterols.When containing soy protein material in the compositions, preferably there are about 5 Ke-Yue 100 gram soy protein materials in the compositions, more preferably there are about 10 Ke-Yue 40 gram soy protein materials.When containing isoflavone in the compositions, preferably there are about 10 milligrams-Yue 1000 milligrams of isoflavone in the compositions, more preferably there are about 25 milligrams-Yue 200 milligrams of isoflavone.
In a preferred scheme, plant sterol and soy protein material and/or isoflavone and suitable excipient are mixed with medicine or OTC (over-the-counter) delivery system.The medicine or the OTC (over-the-counter) preparation that contain plant sterol and soy protein material and/or isoflavone can be by conventional method preparations known in the art.For example, composition of the present invention can be mixed with tablet, capsule, powder, suspending agent and be used for the solution that parenteral introduction comprises intravenous, intramuscular and subcutaneous administration with carrier, binding agent, diluent and excipient with common commonly used, and is mixed with the solution that is used for transdermal usefulness patch.
The pharmaceutically acceptable excipient of inertia that is used to form medicine of the present invention or OTC (over-the-counter) preparation comprises starch, mannitol, calcium sulfate, dicalcium phosphate, magnesium stearate, silicon derivative and/or sucrose, for example sucrose, lactose and glucose.Binding agent comprises carboxymethyl cellulose and other cellulose derivatives; Gelatin; Natural and synthetic glue class comprises alginate, as sodium alginate; Polyethylene Glycol; With wax etc.Be used for diluent of the present invention and comprise suitable oil; Saline; Sugar juice, for example dextrose aqueous solution or D/W; And glycols, for example Polyethylene Glycol or polypropylene glycol.Other excipient comprise lubricant, for example enuatrol, sodium acetate, sodium stearate, sodium chloride, sodium benzoate, Talcum and magnesium stearate etc.; Disintegrating agent comprises agar, calcium carbonate, sodium bicarbonate, starch and xanthan gum etc.; Adsorptive support is for example bentonite and Kaolin.Also can add coloring agent and aromatic in medicine or the OTC (over-the-counter) preparation.
In another preferred scheme, the food supplementation that has mixed plant sterol and soy protein material and/or isoflavone can be prepared as follows: various compositions are added in the food as food composition, perhaps various mixture of ingredients are added in the food as food composition.The food that can add these compositions comprises nearly all food, but most preferably wherein soy protein material or the vegetable oil that contains plant sterol are used as the food of functional components.For example, plant sterol and soy protein material and/or isoflavone can be added to following food, include, but not limited to meat, for example minced meat, emulsified meat and butcher's meat; Beverage, for example nutritious drink, sports drink, protein-enrichmen beverage, fruit juice, milk, milk substitute and weight-reducing drinks; Cheese, for example rat cheese and soft cheese, cheese and rural cheese; Freezing point, for example ice cream, ice are suckled, the low fat freezing point, and non-newborn class freezing point; Yoghourt; Soup; Pudding; Bakery product; Salad dressing; And dip in beans and be coated with beans (dips and spreads), for example mayonnaise and French fries beans.Most preferably plant sterol, soy protein material and isoflavone or plant sterol and soy protein material mix the formation emulsion in aqueous slurry, this emulsion especially can be used for emulsified food and beverage, for example salad dressing, yoghourt, soybean cheese, emulsified meat and powder drink.
Following non-limiting preparation illustrated comprise the present composition and can be used for the plant sterol of the inventive method and the medicine and the food of soybean protein and/or isoflavone compounds.
Preparation
Following series preparation 1-4 has illustrated and has comprised the plant sterol that is used for the present composition and the medicine or the OTC (over-the-counter) preparation of soybean protein and/or isoflavone.Preparation 1
Gelatine capsule
Prepare hard gelatin capsule with following ingredients: isoflavone 25-100 milligram/capsule; Plant sterol 500-2000 milligram/capsule; Starch, NF 0-1000 milligram/capsule; But flow starch powder 0-1000 milligram/capsule; Polyorganosiloxane fluid 350 centistoke 0-20 milligram/capsules.Each composition is mixed, sieve and be filled in the capsule.Preparation 2
Tablet
Prepare tablet with following ingredients: plant sterol 250-500mg/ sheet; Soy protein material 1000-2000mg/ sheet; Microcrystalline Cellulose 20-300mg/ sheet; Starch 0-50mg/ sheet; Magnesium stearate or stearic acid 0-15mg/ sheet; Silicon dioxide, atomizing, 0-400mg/ sheet; Silicon dioxide, colloidal, the 0-1mg/ sheet; With lactose 0-100mg/ sheet.Various compositions mixing and compacting are in blocks.Preparation 3
Suspending agent
Prepare suspending agent with following ingredients: isoflavone 0.1-200mg/5ml; Plant sterol 250-2000mg/5ml; Soy protein material 500-2000mg/5ml; Sodium carboxymethyl cellulose 50-700mg/5ml; Sodium benzoate 0-10mg/5ml; Pure water 5ml; Aromatic as required and coloring agent.Preparation 4
Non-gastrointestinal solution
The active component (active component is that weight ratio is 5: 4: 1 soy protein material, plant sterol and an isoflavone) of 1.5% (weight) is stirred the non-gastrointestinal compositions of preparation in the aqueous solution of propylene glycol of 10% (volume).With sodium chloride this solution is transferred to etc. and to ooze and sterilize.
Following series preparation 5-8 has illustrated the plant sterol that uses in the available present composition and has been rich in the food supplementation of the soy protein isolate formation of isoflavone compounds.Every gram soybean protein contains the about 7 milligrams isoflavone compounds of the 1-that has an appointment usually in the soy protein isolate that is rich in isoflavone in the following example.Preparation 5
Promptly use beverage
Promptly form by following ingredients with beverage:
The percentage by weight that becomes to be grouped into
Water 75-82
Be rich in the soy protein isolate 10-15 of isoflavone
Plant sterol 3-5
Sucrose 5-8
Cocoa powder 0.1-1
Vitamin/mineral 0.1-1
Essence 0.1-1
Cellulose gel 0.1-0.5
Promptly containing the 20 gram isolating soybean proteins (comprising about 20-240 milligram isoflavone compounds) and about 6 of having an appointment and restrain plant sterols with every part of 8 ounces of uses with beverage.Preparation 6
Powder drink
Powder drink is formed by following ingredients:
The percentage by weight that becomes to be grouped into
Be rich in the soy protein isolate 75-85 of isoflavone
Plant sterol 5-10
Sucrose 8-15
Maltodextrin 1-5
Vitamin/mineral 0.5-2
Aspartame 0-0.5
Essence 0-0.5
30 gram powder drink goods are added to form in the water contain the serving that about 23 gram soy protein isolates (comprising about 23161 milligrams of isoflavone compounds) and about 2.5 restrain plant sterols.Agent 7
Food bar
Food bar is formed by following ingredients:
The percentage by weight that becomes to be grouped into
Be rich in the soy protein isolate 20-30 of isoflavone
Plant sterol 1-5
Semen Maydis pulp 30-45
Rice slurry solid 7-14
Glycerol 1-5
Cocoa powder 2-7
Compound coating 15-25
The food bar of using with every part 70 gram contains have an appointment 15 gram soy protein isolates (comprising the about 105 milligrams of isoflavone compounds of about 15-) and about 2 gram plant sterols.Preparation 8
Bean yoghourt
Bean yoghourt is formed by following ingredients:
The percentage by weight that becomes to be grouped into
Water 50-70
Be rich in the soy protein isolate 5-15 of isoflavone
Plant sterol 5-15
Sucrose 3-8
Corn starch 1-5
Dextrin 0.3-1
Cellulose gel 1-3
Culture (cultured milk) 0.01-0.1
Fruit 10-20
Vitamin/mineral 0.05-0.3
The bean yoghourt that uses with every part 170 gram contains have an appointment 17 gram soy protein isolates (containing the about 170 milligrams of isoflavone compounds of about 17-) and 17 gram plant sterols.Method
The invention still further relates to method with the concentration of plant sterol and soy protein material and/or isoflavone compounds reduction human blood low-density lipoprotein cholesterol or T-CHOL.For reducing the concentration of blood LDL cholesterol and T-CHOL, incessantly regularly, give the co-administered plant sterol of people and soy protein material and/or isoflavone compounds preferred every day.Cupreol, campesterol, stigmasterol, sitostamol or campestanol that plant sterol is preferably above-mentioned.Based on the dry weight of soy protein material, soy protein material is soybean hypocotyl material or the soy protein material that contains at least 49% soybean protein, for example big bean flour, particle, concentrate or separator.Isoflavone compounds is selected from one or more above-mentioned genisteins, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring glucosides and glucosides conjugate.Plant sterol and soy protein material and/or isoflavone preferably use with above-mentioned medicine or OTC (over-the-counter) compositions or as the food supplementation form, and this depends on which kind of approach is more effective and/or is easy to accept.
Plant sterol and soy protein material and/or isoflavone compounds can simultaneously or use in order in certain period of time, preferred every day cyclic application.Most preferably that plant sterol and soy protein material and/or isoflavone compounds is simultaneously co-administered with the form of the above-mentioned present composition.Perhaps plant sterol and soybean protein and/or isoflavone compounds are used as the independent element order." in proper order " be meant in certain period of time,, and be not limited to use continuously at once various compositions as the various compositions of individual application in a day.
Plant sterol and soy protein material and/or isoflavone compounds are to be applied to the people with the amount that each component effectively reduces the human blood cholesterol concentration.The given dose that each component effectively reduces blood cholesterol levels concentration depends on several factors, comprises the people's who is applied body weight, blood cholesterol levels concentration and route of administration.The plant sterol application dosage that reduces blood cholesterol levels is preferably 500 mg/day to 50 gram/skies, and more preferably 1 gram/sky is used incessantly to 5 gram/skies.If use soy protein material, the soy protein material application dosage that then reduces blood cholesterol levels is preferably 5 gram/skies to 100 gram/skies, and more preferably 10 gram/skies are to 30 gram/skies.If use isoflavone, the application dosage that then reduces the isoflavone compounds of blood cholesterol levels is preferably 10 mg/day to 1000 mg/day, more preferably 25 mg/day to 200 mg/day.
When with the amount that effectively reduces LDL and total cholesterol concentration separately when co-administered, collaborative these cholesterol concentrations that reduce the people of plant sterol and soy protein material and/or isoflavone.The plant sterol that uses in the inventive method, soy protein material and isoflavone are by LDL and total blood cholesterol levels concentration in conjunction with the reduction people of different mechanism or different mechanisms, and these mechanism are juxtaposition to a certain extent.It is believed that the mechanism of each the component cholesterol reducing in these materials and this class mechanism of other materials interact, and have quickened the activity of other material cholesterol reducing mechanism.The acceleration of the cholesterol reducing mechanism of the blending ingredients of cholesterol reducing causes the comprehensive reduction of LDL and total cholesterol concentration in the blood, the blood LDL that this reduction effect produces separately greater than various compositions and the reduction effect of total cholesterol concentration.
For example, co-administered plant sterol, soy protein material and isoflavone can be worked in coordination with several aspects that the mechanism that reduces blood LDL and total cholesterol concentration combines the every kind of material cholesterol reducing mechanism that is proposed.The known plants sterol has by stoping small intestinal to the equilibrated effect of enterohepatic circulation between the inhalation effects cholesterol of food cholesterol and cholic acid.The cholesterol feedback that this has reduced in the intestinal liver cholesterol circulation adjusting causes and synthesizes the needs of cholic acid to cholesterol in the liver.Liver can obtain essential cholesterol by the LDL cholesterol receptor in the hepatocyte from blood, LDL cholesterol receptor can obtain raising by using plant sterol, perhaps can synthesize required cholesterol.If the required cholesterol of picked-up liver, then cholesterolemia lowering of concentration from blood.
A kind of mechanisms known of LDL and total cholesterol concentration is that the cholic acid that increases feces is drained in the soybean protein reduction blood.The cholic acid of feces is drained to increase and is caused liver to produce more cholic acid, need utilize cholesterol as substrate in the generation of cholic acid.As mentioned above, liver can obtain the synthetic cholic acid of cholesterol from blood, thereby reduces blood cholesterol levels concentration.
According to the present invention, co-administered plant sterol and soybean protein can be worked in coordination with and be adjusted intestinal liver cholesterol homoiostasis, and the result obviously reduces LDL and the total cholesterol concentration in the blood.Plant sterol can produce liver cholesterol deficiency to the inhibitory action of the little intestinal absorption of food cholesterol, thisly can not obtain part and alleviates by replenish cholesterol from blood completely.The excretory increase of feces cholic acid that soybean protein causes can aggravate to eliminate liver cholesterol deficiency that cholesterol cause by increasing with cholic acid substrate form from liver by plant sterol, and this deficiency obtains part by the cholesterol that draws other from blood and alleviates.
Effectively collaborative LDL of reduction of isoflavone associating plant sterol that uses among the present invention or plant sterol and soy protein material and total cholesterol concentration, partly cause is LDL cholesterol-acceptor quantity that isoflavone could raise or increase liver.The isoflavone that uses among the present invention is genistein, daidzein, Glycitein, formononetin, biochanin A and their naturally occurring separately glucosides and glucosides conjugate, and they are the phytoestrogens that have estrogen action in the known body.Estrogen increases the quantity of liver L DL cholesterol receptor, and this receptor has improved LDL cholesterol granule enters liver from blood plasma clearance rate.According to the present invention, rise by the inductive liver L DL cholesterol of the estrogen action of one or more isoflavone receptor or quantity increase, and enter liver with can obviously promoting the LDL cholesterol to remove from blood by plant sterol and/or the inductive liver of soy protein material to the increase in demand of cholesterol.
Yet method of the present invention is not limited to the specific mechanism of action, because co-administered plant sterol, one or more isoflavone, and/or soy protein material reduces, and the mechanism of LDL and total cholesterol concentration has several in the blood.For example soybean protein is except that draining the change cholesterol homoiostasis by increasing cholic acid, because its homoarginine content, specific effect that also can be by proteic 7S storage unit, the metabolism by cholesterol in the scale effect liver that changes serum glucagon and serum insulin or by increasing the concentration of LDL and T-CHOL in the thyroxinic concentration reduction blood that dissociates in the serum.Plant sterol also reduces cholesterol by the mechanism beyond the cholesterol absorption that suppresses small intestinal, because plant sterol can come the cholesterol reducing level by direct injection blood flow according to the show.
The invention still further relates to by stoping or slow down the method for progression of atherosclerosis for co-administered plant sterol of people and soy protein material and/or at least a isoflavone, described soy protein material is soybean hypocotyl material or the soy protein material that contains at least 49% (weight) soybean protein, and described isoflavone is selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring separately glucosides.Plant sterol is a kind of in cupreol, campesterol, stigmasterol, sitostamol or the campestanol preferably.Soy protein material is Semen sojae atricolor powder, Semen sojae atricolor particle, soybean protein concentrate or soy protein isolate preferably.Preferred application process and dosage are with top described identical about using plant sterol and soy protein material and/or isoflavone for the LDL of reduction blood and total cholesterol concentration.
As mentioned above, when administration of human is enough to all cpds of cholesterol reducing live vol, effectively collaborative blood LDL and the total cholesterol concentration of reducing of plant sterol and soy protein material and/or isoflavone.The rising of LDL cholesterol levels is relevant with development of atherosclerosis in the blood, because the LDL cholesterol is the key component of atherosclerotic formation.Therefore, the associating of plant sterol, soy protein material and/or the isoflavone of reduction LDL cholesterol can effectively stop or alleviate development of atherosclerosis.
In a preferred scheme, no matter whether use soy protein material, isoflavone always is used for prevention or slows down development of atherosclerosis with plant sterol is co-administered, because isoflavone also provides the atherosclerosis activity except that reducing blood LDL cholesterol concentration.Especially, these isoflavone provide effective protective effect to the atherosclerosis of blood vessel level.Isoflavone-especially Aglucone isoflavone genistein, daidzein, biochanin A and formononetin suppress the oxidation of LDL cholesterol.The oxidation of LDL cholesterol is the committed step of atherosclerotic formation, because the oxidation of LDL cholesterol can improve its atherosclerotic formation ability.Some isoflavone, especially genistein, daidzein and biochanin A or tyrosine kinase inhibitor, they suppress the formation of atherosclerotic lesions and thrombin by the activity that suppresses tyrosine kinase.Therefore, according to the present invention, co-administered plant sterol and at least a isoflavone are perhaps united and are used they and soy protein material to reduce LDL and total cholesterol level and mechanism prevention or alleviation development of atherosclerosis by suppressing atherosclerotic formation and growth in the blood by collaborative.
Embodiment 1
Select five to 50 male and carry out clinical research.These male are diagnosed as and suffer from moderate or severe hypercholesterolemia, and for example total blood cholesterol levels is 250mg/dl or higher.These male are divided into five groups, first winding is subjected to 30 to restrain the not isolating soybean protein food supplementation of isoflavone-containing (extracting the isoflavone of removing wherein by alcohol) (" Semen sojae atricolor " group), second winding is subjected to 5 grams to contain the plant sterol food supplementation (" plant sterol " group) of cupreol, the 3rd winding is subjected to 75 milligrams of isoflavone food supplementations (" isoflavone " group) that contain isoflavone genistein and daidzein, the 4th winding is contained the isolating soybean protein of 30 grams, the food supplementation of 5 gram plant sterol cupreols and 75 milligrams of isoflavone genisteins and daidzein (" associating " group) is not accepted food supplementation (" contrast " organized) for the 5th group.Select the diet of each group so that do not comprise other isoflavone, plant sterol and soybean protein source, and two groups are not used the diet that comprises the estrogen source.Continued to take 6 months.
Before beginning to take, measure patient's T-CHOL and low density lipoprotein, LDL cholesterolemia datum-plane.Take separately diet after 6 months in each group, measure and respectively organize the benchmark symptom.Compare each group membership and each member result when research beginning and end.The reduction percent of LDL and total blood cholesterol levels is higher than the activity that Semen sojae atricolor group, plant sterol group, isoflavone group and the co-administered as can be seen plant sterol of matched group, soy protein material and isoflavone have improved reduction LDL or total blood cholesterol levels from unite group.
The associating agent of plant sterol and soy protein material and/or isoflavone reduces people's LDL and the practicality of blood total cholesterol concentration has obtained confirmation by top embodiment.
Embodiment 2
Select five to 50 women to carry out clinical research.These women are postclimacteric and are suffered from atherosclerosis by diagnosis, that is, are diagnosed as and have the atherosclerotic plaque that comprises narrow speckle and closed speckle.These women are divided into five groups, first winding is subjected to 30 to restrain the not isolating soybean protein food supplementation of isoflavone-containing (extracting the isoflavone of removing wherein by alcohol) (" Semen sojae atricolor " group), second winding is subjected to 5 grams to contain the plant sterol food supplementation (" plant sterol " group) of cupreol, the 3rd winding is subjected to 75 milligrams of isoflavone food supplementations (" isoflavone " group) that contain isoflavone genistein and daidzein, the 4th winding is contained the isolating soybean protein of 30 grams, the food supplementation of 5 gram plant sterol cupreols and 75 milligrams of isoflavone genisteins and daidzein (" associating " group) is not accepted food supplementation (" contrast " organized) for the 5th group.Select respectively to organize diet so that do not comprise other isoflavone, plant sterol and soybean protein source, and two groups are not used the diet that comprises the estrogen source yet.Continued to take 6 months.
Before beginning to take, measure total cholesterolemia datum-plane of patient; High density and low density lipoprotein, LDL blood cholesterol levels; Estrogen level; Degree with the narrow and atherosclerotic plaque of the selected blood vessel (for example femur shallow artery and arm shallow artery) that carries out the reactive research of the non-dipped type of blood vessel (for example using high resolution ultrasonic).Take separately diet after 6 months in each group, measure again and respectively organize the benchmark symptom.Compare between each group membership and the result of each member when research beginning and end.With cupreol, isolating soybean protein, isoflavone genistein with daidzein and do not use their situation to compare, the high atherosclerosis activity of chemical compound associating agent, by uniting group with respect to Semen sojae atricolor group, plant sterol group, isoflavone group and the atherosclerotic plaque of matched group and reducing greatly of restenosis, or the increase of atherosclerotic plaque and restenosis minimum degree is illustrated.
The practicality that prevents the uniting of plant sterol and soy protein material and/or isoflavone or alleviate the development of the atherosis speckle of human artery has obtained confirmation by top embodiment.
Claims (25)
1, a kind of sterol compositions is characterized in that it contains
(A) account for composition weight at least 0.49% plant sterol and
(B) a kind of in the following ingredients (a)-(d):
(a) a kind of soy protein material, described soy protein material contains the soybean protein that accounts for soy protein material dry weight at least 49%;
(b) at least a isoflavone, described isoflavone are selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring glucosides and glucosides conjugate;
(c) soybean hypocotyl material;
(d) composition (a) and (b).
2, the compositions of claim 1, it contains:
A kind of soy protein material, described soy protein material contains the soybean protein that accounts for soy protein material dry weight 49% at least;
At least a isoflavone, described isoflavone are selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring glucosides and glucosides conjugate; With
One plant sterols, wherein said plant sterol accounts at least 0.49% of described composition weight.
3, the compositions of claim 1, it contains:
A kind of soy protein material, described soy protein material contains the soybean protein that accounts for soy protein material dry weight 49% at least; With
One plant sterols, wherein said plant sterol accounts at least 0.49% of described composition weight.
4, the compositions of claim 1, it contains:
At least a isoflavone, described isoflavone are selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring glucosides and glucosides conjugate; With
One plant sterols, wherein said plant sterol accounts at least 0.49% of described composition weight.
5, the compositions of claim 1, contain:
The soybean hypocotyl material; With
One plant sterols, wherein said plant sterol accounts at least 0.49% of described composition weight.
6, claim 2 or 3 compositions, wherein said soy protein material is a kind of soy protein isolate.
7, claim 2 or 3 compositions, wherein said soy protein material are selected from down at least a in the group: soybean protein concentrate, big bean flour or Semen sojae atricolor particle.
8, the compositions of claim 1, wherein said plant sterol are at least a cupreol, campesterol, stigmasterol, sitostamol or campestanol.
9, claim 2 or 4 compositions, wherein said isoflavone accounts for 0.0066% of described composition weight at least.
10, claim 2,3 or 4 compositions, it also contains excipient, and wherein said plant sterol, described soy protein material, described isoflavone and described mixed with excipients are medicine or OTC (over-the-counter) preparation.
11, the compositions of claim 10, wherein said medicine or OTC (over-the-counter) preparation are tablet, capsule, powder, suspending agent or solution.
12, claim 2,3 or 4 compositions, it also contains water, and wherein said plant sterol, described soy protein material, described isoflavone and described water mix and form aqueous emulsions.
13, the compositions of claim 12, it is impregnated in the foodstuff.
14, the compositions of claim 5, it also contains at least a isoflavone, and described isoflavone is selected from genistein, daidzein, Glycitein, biochanin A, formononetin and their naturally occurring glucosides and glucosides conjugate.
15, a kind of method that reduces the concentration or the prevention of human blood T-CHOL and low-density lipoprotein cholesterol or slow down progression of atherosclerosis, this method comprises the compositions of using claim 1 in the mode of using each composition simultaneously or sequentially.
16, the method for claim 15, the co-administered of wherein said each composition carries out simultaneously.
17, the method for claim 15, the co-administered of wherein said each composition is in sequence.
18, the method for claim 15, wherein said plant sterol is used with the dosage of about 500mg/ days-Yue 50g/ days.
19, the method for claim 15 is wherein used the compositions of claim 2 or 3, and described soy protein material is used with the amount of about 5g/ days-Yue 100g/ days.
20, the method for claim 15 is wherein used the compositions of claim 2 or 4, and described isoflavone is used with the amount of about 10mg/ days-Yue 1000mg/ days.
21, the method for claim 15, wherein said plant sterol are at least a cupreol campesterol, stigmasterol, sitostamol or campestanol.
22, the method for claim 15 is wherein used the compositions of claim 2 or 3, and described soy protein material is selected from least a soybean protein concentrate, soy protein isolate, big bean flour and Semen sojae atricolor particle.
23, the method for claim 15, wherein said compositions or described composition are used with the form of food.
24, the method for claim 15, wherein said compositions or described composition are used with medicine or OTC (over-the-counter) dosage form.
25, the method for claim 24, wherein said medicine or OTC (over-the-counter) preparation are tablet, capsule, powder, suspending agent or solution.
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| CNA2006101711241A CN1981772A (en) | 2000-05-13 | 2000-05-13 | Composition and method for decreasing concentration of low density lipoprotein cholesterol |
| CN00120362A CN1323544A (en) | 2000-05-13 | 2000-05-13 | Compositions and methods for lowering low-density lipoprotein cholesterol concentrations |
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| CN00120362A CN1323544A (en) | 2000-05-13 | 2000-05-13 | Compositions and methods for lowering low-density lipoprotein cholesterol concentrations |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1327788C (en) * | 2001-12-18 | 2007-07-25 | 有限会社大长企画 | Health-care food |
| WO2008120105A3 (en) * | 2007-03-30 | 2009-02-05 | 9898 Ltd | Pharmaceutical platform technology for the development of natural products |
| CN101564061B (en) * | 2009-05-25 | 2012-07-04 | 内蒙古蒙牛乳业（集团）股份有限公司 | Double-protein liquid milk and preparation method thereof |
| CN102917603A (en) * | 2010-06-07 | 2013-02-06 | 不二制油株式会社 | Fat-reduced soybean protein material, soybean emulsion composition, and their production methods |
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| CN105998045A (en) * | 2016-06-27 | 2016-10-12 | 王双喜 | Pharmaceutical composition for treating atherosclerosis and application thereof |
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- 2000-05-13 CN CNA2006101711241A patent/CN1981772A/en active Pending
- 2000-05-13 CN CN00120362A patent/CN1323544A/en active Pending
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| CN1327788C (en) * | 2001-12-18 | 2007-07-25 | 有限会社大长企画 | Health-care food |
| WO2008120105A3 (en) * | 2007-03-30 | 2009-02-05 | 9898 Ltd | Pharmaceutical platform technology for the development of natural products |
| CN101790682A (en) * | 2007-03-30 | 2010-07-28 | 9898有限公司 | Technologies for developing medicinal platforms of natural products |
| CN101564061B (en) * | 2009-05-25 | 2012-07-04 | 内蒙古蒙牛乳业（集团）股份有限公司 | Double-protein liquid milk and preparation method thereof |
| CN104351459A (en) * | 2010-06-07 | 2015-02-18 | 不二制油株式会社 | Fat-reduced soybean protein material and soybean emulsion composition, and processes for production thereof |
| CN102917603A (en) * | 2010-06-07 | 2013-02-06 | 不二制油株式会社 | Fat-reduced soybean protein material, soybean emulsion composition, and their production methods |
| CN102917603B (en) * | 2010-06-07 | 2015-06-17 | 不二制油株式会社 | Fat-reduced soybean protein material, soybean emulsion composition, and their production methods |
| US9307778B2 (en) | 2010-06-07 | 2016-04-12 | Fuji Oil Holdings Inc. | Fat-reduced soybean protein material and soybean emulsion composition, and processes for production thereof |
| CN103596442A (en) * | 2011-06-07 | 2014-02-19 | 不二制油株式会社 | Novel application of reduced-fat soybean protein material to soybean-derived raw material-containing food or beverage |
| CN107531772A (en) * | 2015-05-07 | 2018-01-02 | 肿瘤免疫股份有限公司 | Use of CD24 for lowering low density lipoprotein cholesterol levels |
| CN107531772B (en) * | 2015-05-07 | 2021-09-21 | 肿瘤免疫股份有限公司 | Use of CD24 for reducing low density lipoprotein cholesterol levels |
| CN105998045A (en) * | 2016-06-27 | 2016-10-12 | 王双喜 | Pharmaceutical composition for treating atherosclerosis and application thereof |
| CN109414467A (en) * | 2016-07-13 | 2019-03-01 | J-制油株式会社 | Metabolic syndrome inhibitor |
| CN113367338A (en) * | 2021-05-17 | 2021-09-10 | 山西大学 | Application of millet rice bran active polyphenol in preparation of products for preventing and treating atherosclerosis |
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