CN103167869A - Functional food compositions and methods - Google Patents

Functional food compositions and methods Download PDF

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Publication number
CN103167869A
CN103167869A CN2011800498488A CN201180049848A CN103167869A CN 103167869 A CN103167869 A CN 103167869A CN 2011800498488 A CN2011800498488 A CN 2011800498488A CN 201180049848 A CN201180049848 A CN 201180049848A CN 103167869 A CN103167869 A CN 103167869A
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carrier
food
bioactivator
functional food
lipid
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CN2011800498488A
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多伦·弗里德曼
吉迪恩·施特拉斯曼
阿舍尔·施穆勒维茨
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Clearfarma Ind Ltd
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Clearfarma Ind Ltd
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    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
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    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A23L21/00—Marmalades, jams, jellies or the like; Products from apiculture; Preparation or treatment thereof
    • A23L21/20—Products from apiculture, e.g. royal jelly or pollen; Substitutes therefor
    • A23L21/25—Honey; Honey substitutes
    • A—HUMAN NECESSITIES
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    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/10—Foods or foodstuffs containing additives; Preparation or treatment thereof containing emulsifiers
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
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    • A23P10/00—Shaping or working of foodstuffs characterised by the products
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Abstract

A functional food and a method of producing same are provide. The functional food is produced by mixing a lipid solvent including a bioactive agent with a semi-solid or liquid food base carrier until formation of an emulsion that includes solid lipid particles loaded with the bioactive agent.

Description

Functional food composite and preparation method thereof
Technical field and background technology
The present invention relates to comprise the compositions of bioactive ingredients, described bioactive ingredients is carried in the solid lipid granule that is scattered in the food carrier is carrier, the invention still further relates to the method for the described compositions of preparation.
Health food, the term that is namely combined by " nutrition " and " medicine " two meaning of a word is that health and medical effect can be provided, and comprises food or the food product of prevention and treatment disease.Together with other classifications, health food can comprise that functional food and medical diets etc. are [referring to Chen et al.Trends in Food Science﹠amp; Technology17(2006) 272-283; With Lemes and McClements Trends in Food Science﹠amp; Technology20(2009)].
Functional food is near the consumption of the form of its native state, and comprises special medicine that except the Nutrition of described food (or replenishing as it) can be provided or component or the composition of physiologic effect.Comprising the Bulbus Allii and the fish that comprises omega-3 fatty acid of sulfur-containing compound, is the example of functional food.Functional food can be by reinforced or strengthen and reproduce or nutritional labeling or the physiological effect of supplement.
Medical diets is prepared under physician guidance and is used or take orally, and is used to the dietary management of disease or the symptom of special dietary demand.
Will be such as vitamin, probiotic bacteria, the bioactive ingredients such as biologically active peptide and antioxidant mixes in the food carrier is carrier, and a kind of straightforward procedure of development of new functional food is provided, and described functional food may have physiological benefit maybe can reduce onset risk.But, so far, functional and medical diets is subject to the load capability (that is, the concentration of described bioactivator in the food carrier is carrier) of its bioactivator usually, particularly can not dissolve easily in described food carrier is carrier or all the more so during emulsifying when described activating agent.
The bioactive food composition is the biomolecule that is present in such as in the food such as fruits and vegetables, and it has the ability of regulating one or more metabolic processes, therefore can be used to treat disease and health invigorating.
The bioactive food composition can be used as the part in food source and takes in or take in purified form.But, because bioavailability is limited, in many instances, do not know whether the intake of these compositions is effective doses that the health centre needs.
The method that improves bioactive food composition bioavailability is well known in the art, and comprise for strengthen the bioactive food composition absorb in gastrointestinal tract (GI) and/or limit it at gastrointestinal tract or vivo degradation and the formula that designs (referring to, Davis, DDT, Volume10, Number4, Feb.2005).
Although described formula can be used for improving the bioavailability of bioactive food composition, biomolecule from food is difficult to because foul smell or abnormal flavour are arranged take in usually, therefore can not provide and the corresponding nutritive value of this food that obtains described bioactive food composition.
Therefore, still need to have obtained to overcome at present the compositions that comprises Basal nutrition and bioactive ingredients of defects.
The invention provides a kind of physiologic function compositions based on food, said composition can by the bioactivator of oral delivery physiology effective dose, successfully overcome the defective of present known product.
Except as otherwise noted, all scientific and technical terminologies of using of this paper have with those of ordinary skills the identical meanings generally understood.Although similarly or be equal to the disclosed method of this paper and material can be used for implementing or check the present invention, suitable method and material are as mentioned below those.Just in case conflict occurs, will use patent specification, comprise that these definition control it.In addition, material, method and embodiment are only illustrative, rather than determinate.
Summary of the invention
An object of the present invention is to provide a kind of method for preparing functional food, comprising:
Melt lipid solvent under the condition that has the lipophilic bioactive agent;
The lipid solvent of melting and bioactivator are heated to temperature are at least 65 ℃;
The food carrier is carrier is added in the lipid solvent and bioactivator of described thawing; With,
The lipid solvent of the described thawing of emulsifying, described bioactivator and described food carrier is carrier, until form emulsion, described emulsion comprises the lipid granule that contains described bioactivator.
Another object of the present invention is to provide method as hereinbefore defined, wherein, describedly the lipid solvent of melting and bioactivator are heated to step that temperature is at least 65 ℃ comprise one the lipid solvent of described thawing and bioactivator are heated to temperature is the step of 70 ℃-90 ℃.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described emulsifying step is at least part of to carry out simultaneously with a cooling step.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described cooling step further comprises and temperature is cooled to the step of about 45 ℃.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described cooling step further comprises temperature is cooled to step than low at least 20 ℃ of emulsifying temperature.
Another object of the present invention is to provide method as hereinbefore defined, before also being included under the condition that has described bioactivator the step of melting described lipid solvent, under the condition of described bioactivator, heating emulsification agent to temperature is at least 90 ℃ existing.
Another object of the present invention is to provide method as hereinbefore defined, wherein, and the group that described emulsifying agent selects free PEG ester and sucrose ester to form.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described emulsifying agent is a kind of PEG ester, selects free PEG6000 ester, the group that PEG-100 stearate and PEG40 stearate form.
Another object of the present invention is to provide method as hereinbefore defined, also comprise one in the lipid solvent of described food carrier is carrier being added to described thawing and bioactivator before the step of at least a portion of heated food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, wherein, the step of at least a portion of described heated food carrier is carrier comprises that the first with described food carrier is carrier is heated to the first predetermined temperature, and the second portion of described food carrier is carrier is heated to the second predetermined temperature lower than described the first predetermined temperature.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described the first predetermined temperature is at least 60 ℃, and described the second predetermined temperature is no more than 50 ℃.
Another object of the present invention is to provide method as hereinbefore defined, wherein, the step of described interpolation food carrier is carrier further comprises the first that adds described food carrier is carrier, and comprise a step of adding the second portion of described food carrier is carrier during described emulsifying step, the step of the described second portion of described interpolation can only in the situation that the temperature of other emulsified compositions carry out lower than 60 ℃.
Another object of the present invention is to provide method as hereinbefore defined, also comprises:
A part to described food carrier is carrier under the condition that potassium sorbate exists heats, until form solution;
With described solution cool to room temperature; With,
Described solution is added in the lipid phase and bioactivator of described thawing.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described food carrier is carrier is at room temperature semi-solid.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described food carrier is carrier is at room temperature liquid.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described bioactivator comprises the bioactive food composition.
Another object of the present invention is to provide method as hereinbefore defined, wherein, the step of melting lipid solvent under described condition there being the lipophilic bioactive agent is included in to exist melts lipid solvent under the condition that is selected from the bioactivator in the group that following material forms: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid, and plant sterol.
Another object of the present invention is to provide method as hereinbefore defined, wherein, and the group that described food carrier is carrier selects free carbohydrate syrup and polysaccharide syrup to form.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described syrup selects free Mel, the group that Fructus Jujubae syrup and maple syrup form.
Another object of the present invention is to provide method as hereinbefore defined, comprises that also one allows at least a portion of described lipid be solidified into the step of granule in described food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, comprises that also one is dispersed in step in described food carrier is carrier with described uniform particles.
Another object of the present invention is to provide method as hereinbefore defined, wherein, the step that allows at least a portion of described lipid be solidified into granule in described food carrier is carrier also comprises allows at least a portion of described lipid be solidified into the step of microsphere in described food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, wherein, the step that allows at least a portion of described lipid be solidified into microsphere in described food carrier is carrier comprises that further one allows at least a portion of described lipid be solidified into the step that diameter is 0.5 μ m-5 μ m microsphere in described food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, wherein, the step that allows described lipid be solidified into granule in described food carrier is carrier further comprises the step of a granule that allows described lipid be solidified into to select the group that free solid particle and semi-solid granule form in described food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, at least 70% of described bioactivator is combined with described granule.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, at least 80% of described bioactivator is combined with described granule.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, the 90%-95% of described bioactivator is combined with described granule.
Another object of the present invention is to provide method as hereinbefore defined, also comprises a step that obtains at least a lipid solvent, and described lipid solvent is selected from the group that following material forms: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
Another object of the present invention is to provide method as hereinbefore defined, also comprises a step that bioactivator is mixed with described food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, the step of wherein, bioactivator being mixed with described food carrier is carrier further comprises the step that the bioactivator that will be selected from vitamin and mineral mixes with described food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, the step that bioactivator is mixed with described food carrier is carrier further comprises a step that the hydrophilic bioactivator is mixed with described food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, wherein, the step that the hydrophilic bioactivator is mixed with described food carrier is carrier further comprises and will be selected from cobalamine, the step that the hydrophilic bioactivator of folic acid and ferrous gluconate mixes with described food carrier is carrier.
Another object of the present invention is to provide a kind of functional food, it contains the lipophilic bioactive agent, lipid and food carrier is carrier, wherein, described lipid is at least part of to be dispersed in described food carrier is carrier with particle form, is included in described granule and described lipophilic bioactive agent is at least part of.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described granule consists of the 5%-40%(w/w of described food).
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described lipophilic bioactive agent is the bioactive food composition.
Another object of the present invention is to provide functional food as hereinbefore defined, wherein, described lipophilic bioactive agent comprises the composition of the group that the free following material of at least a choosing forms: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid and plant sterol.
Another object of the present invention is to provide functional food as hereinbefore defined, wherein, and the group that the free following material of described lipid choosing forms: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described food carrier is carrier is at room temperature liquid.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described food carrier is carrier is at room temperature semi-solid.
Another object of the present invention is to provide functional food as hereinbefore defined, wherein, and the group that described food carrier is carrier selects free carbohydrate syrup and polysaccharide syrup to form.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described syrup selects free Mel, the group that Fructus Jujubae syrup and maple syrup form.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described uniform particles is dispersed in described food carrier is carrier.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described granule comprises microsphere.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, the diameter of described microsphere is 0.5 μ m-5 μ m.
Another object of the present invention is to provide functional food as hereinbefore defined, wherein, and the group that described granule selects free solid particle and semi-solid granule to form.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, at least 70% of described bioactivator is combined with described granule.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, at least 80% of described bioactivator is combined with described granule.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, the 90%-95% of described bioactivator is combined with described granule.
Another object of the present invention is to provide functional food as hereinbefore defined, also comprises emulsifying agent.
Another object of the present invention is to provide functional food as hereinbefore defined, wherein, and the group that described emulsifying agent selects free PEG ester and sucrose ester to form.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described emulsifying agent is the PEG ester, the group that the free following material of described PEG ester choosing forms: PEG6000 ester, PEG-100 stearate and PEG40 stearate.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described food carrier is carrier mixes with at least a extra bioactivator.
Another object of the present invention is to provide functional food as hereinbefore defined, wherein, and the group that described at least a extra bioactivator selects free vitamin and mineral to form.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described at least a extra bioactivator is the hydrophilic bioactivator.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described hydrophilic bioactivator selects free cobalamine, the group that folic acid and ferrous gluconate form.
Another object of the present invention is to provide a kind of to there being the object that needs that the method for at least a bioactivator is provided, comprise and use a kind of functional food, it contains at least a lipophilic bioactive agent that the lipid granule in being dispersed in the food carrier is carrier is combined.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, the described step of using a kind of functional food comprises that is further used an a kind of step with functional food of following at least a feature:
The group that the free following material of described lipophilic bioactive agent choosing forms: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid, and plant sterol; With,
The group that described food carrier is carrier selects free saccharide and polysaccharide syrup to form.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, the described step of using a kind of functional food comprises that is further used an a kind of step that contains the functional food of emulsifying agent.
Another object of the present invention is to provide method as hereinbefore defined, wherein, describedly use a kind of step that contains the functional food of emulsifying agent and further comprise and use a kind of functional food that contains the emulsifying agent that selects the group that free PEG ester and sucrose ester form.
Another object of the present invention is to provide method as hereinbefore defined, wherein, the described step of using a kind of functional food further comprises the step of using the functional food that comprises at least a extra bioactivator, and described at least a extra bioactivator mixes with described food carrier is carrier.
Another object of the present invention is to provide method as hereinbefore defined, wherein, describedly use a kind of step that comprises the functional food of at least a extra bioactivator that mixes with described food carrier is carrier and further comprise the step of using the hydrophilic bioactivator that at least a and described food carrier is carrier mixes.
Another object of the present invention is to provide a kind of method for preparing functional food and comprises:
A. melt the lipid solvent that comprises bioactivator at least at the temperature of 65 ℃; With,
B. the product of the described step of emulsifying (a) and semi-solid food products carrier is carrier are until form the emulsion that comprises the solid lipid granule; Described solid lipid granule comprises described bioactivator.
Another object of the present invention is to provide a kind of method for preparing functional food, comprising:
A. melt the lipid solvent that comprises bioactivator at least at the temperature of 65 ℃; With,
B. emulsifying (a) and liquid food carrier is carrier are until form the emulsion that comprises the solid lipid granule; Described solid lipid granule comprises described bioactivator.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described bioactivator is the bioactive food composition.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described bioactive food composition is curcumin.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described bioactive food composition is DIM.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described food carrier is carrier is Mel.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described lipid solvent comprises at least a composition that is selected from the group that following material forms: castor oil hydrogenated, stearin, Petiolus Trachycarpi oil, Alina TMOil, height-Ω-3 sage oil, Punica granatum L. oil, American Avocado Tree oil, olive oil, and combination in any.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described lipid solvent also comprises emulsifying agent.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described emulsifying agent comprises PEG ester or sucrose ester.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, described temperature is 70-90 ℃.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, (b) is heated at least 65 ℃ with described foodstuff base material before in step.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, the diameter of described solid lipid granule is the 0.5-5 micron.
Another object of the present invention is to provide method as hereinbefore defined, and wherein, step (b) will comprise the described lipid solvent of described bioactivator and described foodstuff base material when carrying out mixture is cooled to the temperature of about 45 ℃ gradually.
Another object of the present invention is to provide a kind of composition of matter, and it comprises the food carrier is carrier,
This food carrier is carrier contains solid lipid granule and at least a bioactivator that is dispersed in wherein, and wherein, at least 80% of described at least a bioactivator is combined with described solid lipid granule.
Another object of the present invention is to provide composition of matter as indicated above, and wherein, described bioactivator is the bioactive food composition.
Another object of the present invention is to provide composition of matter as indicated above, and wherein, described bioactive food composition is curcumin.
Another object of the present invention is to provide composition of matter as indicated above, and wherein, described bioactive food composition is di indolyl methane (DIM).
Another object of the present invention is to provide composition of matter as indicated above, and wherein, described food carrier is carrier is Mel.
Another object of the present invention is to provide composition of matter as indicated above, and wherein, described solid lipid granule comprises the freely at least a composition in the following material group that forms of choosing: castor oil hydrogenated, stearin or Petiolus Trachycarpi oil, Alina TMOil, height-Ω-3 sage oil, Punica granatum L. oil, American Avocado Tree oil, olive oil, and combination in any.
Another object of the present invention is to provide composition of matter as indicated above, also comprises emulsifying agent.
Another object of the present invention is to provide composition of matter as indicated above, and wherein, described emulsifying agent is PEG.
Another object of the present invention is to provide composition of matter as indicated above, and wherein, the diameter of described solid lipid granule is the 0.5-5 micron.
Another object of the present invention is to there being the object that needs that the method for bioactivator is provided, comprise and use a kind of food carrier is carrier, this food carrier is carrier contains solid lipid granule and at least a bioactivator that is dispersed in wherein, wherein, at least 80% of described at least a bioactivator be combined with described solid lipid granule.
Another object of the present invention is to provide method as hereinbefore defined, wherein, uses by oral and enters.
Another object of the present invention is to provide a kind of composition of matter, comprises the Mel carrier, and this Mel carrier contains the solid lipid granule that is dispersed in wherein and the curcumin and/or the DIM that are clipped in described solid lipid granule.
Another object of the present invention is to provide functional food as hereinbefore defined, and wherein, described functional food can be 32 ℃ of stable preservations 3 months.
Another object of the present invention is to provide composition of matter as indicated above, and wherein, described composition of matter can be 32 ℃ of stable preservations 3 months.
A further object of the present invention is to disclose a kind of method that improves the lipophilic bioactive agent concentration in patient body, comprising: described lipophilic bioactive agent is mixed in above-mentioned any functional food; With give the described functional food have the patient who needs to use scheduled volume.
A further object of the present invention is to disclose a kind of method that improves the lipophilic bioactive agent concentration in patient body, comprising: to there being the patient of needs to use above-mentioned any functional food of described lipophilic bioactive agent of containing of scheduled volume.
A further object of the present invention is a kind of method that is used for improving the lipophilic bioactive agent concentration in patient body that discloses above-mentioned any restriction, and wherein, described lipophilic bioactive agent is the bioactive food composition.
A further object of the present invention is a kind of method that is used for improving the lipophilic bioactive agent concentration in patient body that discloses above-mentioned any restriction, wherein, described lipophilic bioactive agent comprises the composition of the group that the free following material of at least a choosing forms: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid and plant sterol.
A further object of the present invention is a kind of method that is used for improving the lipophilic bioactive agent concentration in patient body that discloses above-mentioned any restriction, and wherein, described lipid solvent is selected from the group that following material forms: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
A further object of the present invention is a kind of method that is used for improving the lipophilic bioactive agent concentration in patient body that discloses above-mentioned any restriction, further comprises a step that improves lipophilic bioactive agent concentration described in the described blood samples of patients that needs are arranged.
A further object of the present invention is a kind of method that is used for improving the lipophilic bioactive agent concentration in patient body that discloses above-mentioned any restriction, further comprises the step of lipophilic bioactive agent concentration described in a liver that improves the described patient that needs are arranged.
A further object of the present invention is a kind of method that is used for improving the lipophilic bioactive agent concentration in patient body that discloses above-mentioned any restriction, also comprises the step of lipophilic bioactive agent concentration described in a gastrointestinal mucosa that improves the described patient that needs are arranged.
A further object of the present invention is to disclose a kind of method that is used for the treatment of the disease that can pass through lipophilic bioactive agent improvement, comprise: described lipophilic bioactive agent is mixed in above-mentioned any functional food, and use the described functional food of scheduled volume for the patient who suffers from described symptom.
A further object of the present invention is to disclose a kind of method that is used for the treatment of the disease that can improve by the lipophilic bioactive agent, comprises that above-mentioned any that patient to needs uses scheduled volume comprises the functional food of described lipophilic bioactive agent.
A further object of the present invention is a kind of method that is used for the treatment of the disease that can pass through lipophilic bioactive agent improvement that discloses above-mentioned any restriction, and wherein, described lipophilic bioactive agent is the bioactive food composition.
A further object of the present invention is a kind of method that is used for the treatment of the disease that can pass through lipophilic bioactive agent improvement that discloses above-mentioned any restriction, wherein, described lipophilic bioactive agent comprises the composition of the group that the free following material of at least a choosing forms: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid, and plant sterol.
A further object of the present invention is a kind of method that is used for the treatment of the disease of improving by the lipophilic bioactive agent that discloses above-mentioned any restriction, wherein, and the group that the free following material of described lipid solvent choosing forms: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
a further object of the present invention is a kind of method that is used for the treatment of the disease that can pass through lipophilic bioactive agent improvement that discloses above-mentioned any restriction, wherein, the group that the free following disease of described disease choosing forms: immunological diseases, heart disease, respiratory disorder, inflammation, cancer, leukemia, lymphoma, gastrointestinal cancer, genitourinary system carcinoma disease, breast carcinoma, ovarian cancer, the head and neck cell carcinoma, pulmonary carcinoma, melanoma, the neurological cancer, gastroenteropathy, gastric ulcer, colitis, intestinal tract disease, Crohn disease, colorectal cancer, fatty liver and non-alcoholic stellato-hepatitis (NASH), edema, arthritis, pancreatitis, oculopathy, inflammatory diseases and combination in any thereof.
A further object of the present invention is a kind of method that is used for the treatment of the symptom that can pass through lipophilic bioactive agent improvement that discloses above-mentioned any restriction, wherein, the group that the free following disease of described symptom choosing forms: Respiratory papillomatosis, prostatitis, cataract, anaphylaxis, bronchitis, asthma, celiac disease, non-abdominal cavity Wheat Gluten is responsive, and irritable bowel syndrome.
A further object of the present invention is to disclose a kind of method that patient to suffering from cancer provides auxiliary treatment, comprise by the method for above-mentioned any restriction a kind of functional food is mixed in described lipophilic bioactive agent, and in conjunction with other anticancer therapies, use the described functional food of scheduled volume for described patient.
A further object of the present invention is to disclose a kind of method that patient to suffering from cancer provides auxiliary treatment, comprises in conjunction with other anticancer therapies, and above-mentioned any of using scheduled volume for described patient comprises the functional food of described lipophilic bioactive agent.
a further object of the present invention is to disclose a kind ofly to be used to the patient who suffers from following disease that the therapy that is referred to as Parma is provided, it is the plant-based medicine therapy: solid carcinoma, leukemia, lymphoma, gastrointestinal cancer, genitourinary system carcinoma disease, breast carcinoma, ovarian cancer, the head and neck cell carcinoma, pulmonary carcinoma, melanoma, neurological cancer and sarcoma, also comprise gastroenteropathy, as: gastric ulcer, colitis, intestinal tract disease, Crohn disease, colorectal cancer, fatty liver and non-alcoholic stellato-hepatitis (NASH), edema, arthritis, pancreatitis, oculopathy, inflammatory diseases, comprise by the method for above-mentioned any one restriction a kind of medicine is mixed in described lipophilic bioactive agent.
Brief description of drawings
Only the present invention will be described for form to give an example below in conjunction with accompanying drawing.Specifically see accompanying drawing for details, it is to be noted, shown details is the character of giving an example, and is only to inquire into the preferred embodiments of the invention for illustrative, and the purpose that presents them is to be considered to the most useful and to be convenient to understand the principle of the invention most and the explanation of design feature in order to provide.Thus, not than the basic comprehension attempt that shows CONSTRUCTED SPECIFICATION of the present invention in greater detail required for the present invention, the explanation of doing by reference to the accompanying drawings makes those skilled in the art understand some forms of the present invention and how specifically to implement.
Description of drawings:
Fig. 1 represents the chemical constitution of curcumin and metabolite thereof.
Fig. 2 is the method flow diagram that the explanation preparation is dispersed in the solid lipid fine dispersion of the curcumin (and/or DIM) in Mel.
Fig. 3 is that the granularity that is dispersed in Mel is the MIcrosope image of the curcumin powder particle (crystal) of 5-100 μ m.
Fig. 4 represents to be dispersed in curcumin solid lipid granule (SLPs) MIcrosope image of particle mean size in Mel＜5 μ m; And the MIcrosope image of the curcumin SLPs that is dispersed in water and the curcumin powder that is dispersed in water.
Fig. 5 a-5c is illustrated in and uses curcumin that 400mg/kg do not prepare or according to the curve chart of curcumin content in rat body after the curcumin of one embodiment of the invention preparation.
Fig. 6 a represents when using respectively SLP and Meriva, the variable increment of curcumin concentration in temporal evolution blood plasma (15 minutes, 30 minutes, 60 minutes and 120 minutes).
Fig. 6 b represents when using respectively SLP and Meriva, the variable increment of temporal evolution mucosa curcumin concentration (15 minutes, 30 minutes, 60 minutes and 120 minutes).
The specific embodiment
The content that the below describes in detail, and the description of all chapters and sections of cooperation the present invention make all technical staff of this area can utilize the present invention, and visualize the desired best mode of the enforcement inventor.But, the various improvement that are fit to are apparent to those skilled in the art, because the overall principle of the present invention clearly has been defined as a kind of a kind of functional food and the method for preparing described food that uniqueness is provided.
In addition, the invention provides a kind of can be used for treating disease and sanatory compositions.specifically, the present invention can be used for treating the patient who suffers from such as following disease: the immunological diseases cancer, solid carcinoma, leukemia, lymphoma, gastrointestinal cancer, genitourinary system carcinoma disease, breast carcinoma, ovarian cancer, the head and neck cell carcinoma, pulmonary carcinoma, melanoma, neurological cancer and sarcoma, also comprise gastroenteropathy, as: gastric ulcer, colitis, intestinal tract disease, Crohn disease, colorectal cancer, fatty liver and non-alcoholic stellato-hepatitis (NASH), edema, arthritis, pancreatitis, oculopathy, inflammatory diseases, comprise a kind of following medicine or its combination that will disclose mixed in described lipophilic bioactive agent.
Within the scope of the invention, disclose and a kind ofly be used to the patient who suffers from following disease that the therapy that is referred to as Parma is provided, be i.e. the plant-based medicine therapy: solid carcinoma, gastroenteropathy, as: gastric ulcer, colitis, intestinal tract disease, Crohn disease, colorectal cancer, edema, arthritis, pancreatitis, oculopathy, inflammatory diseases comprises by the following method that will disclose a kind of medicine is mixed in described lipophilic bioactive agent.
With reference to accompanying drawing and the related description principle that the present invention may be better understood and enforcement.
Before in detail explaining at least a embodiment of the present invention, it must be understood that the details that application of the present invention is not limited to following description or the embodiment that enumerates presents.The present invention can adopt other embodiments or implements in every way or realize.In addition, should be understood that word that this paper uses and term for illustration purpose, are not appreciated that determinate.
When enforcement was of the present invention, the inventor had designed a kind of new method for compositions formulated, and said composition contains the food carrier is carrier that mixes with the solid lipid granule that has loaded bioactivator.Compositions of the present invention is conducive to described bioactivator is transported to gastrointestinal tract, and Basal nutrition is provided simultaneously, and elimination or minimizing odour nuisance or the abnormal flavour relevant to described bioactivator.
Therefore, according to one aspect of the present invention, provide a kind of and can be used for treating such as the symptom of the objects such as the mankind or disease or promotion or the compositions of keeping fit.As mentioned below, compositions of the present invention can be used separately or as the ancillary method of other treatment method.
A further object of the present invention is to disclose a kind ofly to be used to the patient who suffers from following disease that the therapy that is referred to as Parma is provided, i.e. the plant-based medicine therapy: solid carcinoma, gastroenteropathy, as: gastric ulcer, colitis, intestinal tract disease, Crohn disease, colorectal cancer, edema, arthritis, pancreatitis, oculopathy, inflammatory diseases comprises by the method for above-mentioned any one restriction a kind of medicine is mixed in described lipophilic bioactive agent.
Compositions of the present invention contains the food carrier is carrier that mixes with the solid lipid granule that has loaded at least a bioactivator.
In this article, phrase " food carrier is carrier " expression is defined as food or from any liquid or the semi-solid combination of food.The example of food carrier is carrier comprises saccharide or polysaccharide syrup, as Mel, and Fructus Jujubae syrup and maple syrup.Preferred naturally comprise high nutrient content and such as the food carrier is carrier of the beneficial elements such as mineral.
In this article, term " granule " represents nanometer or micron particle when being used for the expression solid lipid.
In this article, phrase " bioactivator " expression can produce part or general biology (for example, physiology) effect the material of purification substantially.Bioactive ingredients can comprise one or more bioactivators.Bioactive ingredients can be from the extract of vegetable or fruit or other natural resources.
In this article, when relating to quantity, term " approximately " expression nominal amount ± 10%.
Partly further illustrate as below content and embodiment subsequently, the inventor had designed a kind of new method for the preparation of the present composition already.Described new method can prepare the solid lipid granule (SLPs) that loads described bioactivator in described food carrier is carrier, therefore there is no need at first to prepare the SLPs that described bioactivator loads, and then it is mixed with carrier.Be understandable that, described method can significantly reduce preparation required time, workload and cost.In addition, described method does not need to use harmful organic solvent, as ethanol, and hexanol, ethyl acetate, acetone, (see US Pat.6,086,915) such as ketone or ethyl methyl ketones.
As what disclose in detail in the following embodiments, compositions of the present invention prepares by the following method: melt simultaneously lipophilic bioactive agent and lipid (it is at room temperature solid), being heated to temperature is 65-90 ℃, and the described fused mass of emulsifying in Mel (or similar food carrier is carrier), while is cooling (in preferred embodiments, be cooled to 45 ℃), in order to make described lipid be solidified into solid or semi-solid microsphere in described Mel.
Compositions of the present invention is take some unique properties as feature.Described solid lipid uniform particles is dispersed in described food carrier is carrier, and accounts for the 5-40%(w/w of described compositions).At least 70%(in preferred embodiments, at least 80%; In the most preferred embodiment, 90-95% at least) bioactivator or multiple bioactivator are combined with described solid lipid granule.
This make nearly 30% loading bioactivator can utilize delivery of composition bioactivator of the present invention such as carriers such as Mel.
In addition, the solid lipid granule that is used for carrying secretly described bioactivator can be covered undesirable abnormal smells from the patient or the abnormal flavour relevant to bioactivator, can also prevent that described bioactivator from degrading at gastrointestinal tract.
In addition, the size of the solid lipid granule in the disclosed described functional food of this paper is little and even, therefore be conducive to dissolving and the conveying of its active component of carrying secretly, and be conducive to keep the smooth structure of described food carriers, for example, for curcumin, the SLP wrappage of this activating agent has reduced several times (referring to Fig. 4 a-c) with its granularity (in water).
In addition, discharge the enzymatic degradation that depends on described lipid due to described bioactivator from SLPs, therefore can realize the release that described bioactivator is more controlled and more directed.
At last, the bioactivator that carries due to SLP is to be scattered in stomach (referring to Fig. 4 b) with superfine micronized particle form, and therefore formula of the present invention can significantly improve decomposition and the dissolubility of bioactivator.
As indicated above, the food carrier is carrier of several type is applicable to compositions of the present invention; Such as Mel (undressed or be mainly undressed form), the carriers such as Fructus Jujubae syrup and maple syrup due to its nutrition and mineral/constituent content, are preferred at present.
Mel
The final fruit of labour of bee colony is Mel.Mel contains about 41% fructose.This makes it become the mankind's the sweetest known sugar.It also contains about 35% glucose, about 17% water, about 2% sucrose, and a small amount of mineral and aminoacid.
Mel also contains the trace element of nearly all needed by human.The health-care effect of Mel depends on its quality, and the quality of Mel is subjected to the impact of the pollen of Apis collection.The quality of Mel also depends on processing technique, and the course of processing might be removed a lot of nutrient for plants that are present in green molasses.
Green molasses contains the identical resin that is present on a small quantity in propolis, and described resin is the complex mixture of resin and other materials, and Apis utilizes this mixture sealing Nidus Vespae and defense against bacterial and other microorganism encroach.Be present in the sub-fraction that resin in propolis only accounts for nutrient for plants in propolis and Mel, already confirmed, the other plant nutrient that is dispersed in Mel and propolis has anti-cancer and antitumor properties.Described material comprises the caffeic methyl ester, CAPE and PEDMC.Research worker has found that, described material is in animal body by eliminating two kinds of desmoenzymes, but the activity prevent colon cancer of phosphatidylinositols-specificity phospholipase C and lipoxidase.When green molasses being carried out deep processing and heating, the health-care effect of described nutrient for plants can disappear in a large number.
Fructus Jujubae syrup (Date Syrup)
Fructus Jujubae (Phoenix dactylifera L.) is a kind of important crops of middle east desert area.
Fructus Jujubae is really a kind of high-nutrition food.It is rich in calorie and mineral such as ferrum and potassium, and contains appropriate folic acid, and a small amount of vitamin A and B.Fructus Jujubae is regarded as being conducive to treat anemia, constipation and fatigue.
The denseness of Fructus Jujubae syrup is similar to the denseness of Mel, and color is darker, and has unique fragrance.The Fructus Jujubae syrup contains about 88% saccharide, is mainly glucose and fructose, and is the high-quality source such as the necessary element such as calcium, phosphorus, potassium and magnesium.The Fructus Jujubae syrup is low sodium, is therefore the suitable food for low sodium diet.
Some bioactivators are used to compositions of the present invention, for example, comprise curcumin, silymarin, DIM, genistein, Quercitroside and daidzin (diadezin) etc.The combination of bioactivator, for example, curcumin+di indolyl methane (DIM) or essential fatty acid (EPA and EHA) and plant sterol, as Sitosterolum, stigmasterol, campesterol and brassicasterol also can be used for the present invention.
Disclosed as this paper, described biological activity agent formulation preferably with the solid lipid granule (for example, be entrained in wherein) combination, although under some occasion, described compositions can also comprise the extra bioactivator (for example, vitamin or mineral) that directly mixes with described food carrier is carrier.
Because the solid lipid granule designs in order to carry hydrophobicity (water-insoluble) compound secretly, so the hydrophilic bioactivator is not suitable for SLP and carries secretly, therefore, preferably directly adds in the carrier of the present composition.
Therefore, hydrophobic such as curcumin and DIM and the bioactivators such as Quercitroside and daidzin (diadezin), and therefore be not easy to be blended in the food carrier is carrier, preferably it is entrained in the solid lipid granule of the present composition, and the other biological activating agent, as cobalamine, folic acid and ferrum (as ferrous gluconate) are preferably directly sneaked into the food carrier is carrier of the present composition.
Curcumin
Curcumin---a kind of plant polyphenol is the comestible composition of plant Curcumina longa, the key component of India's curry powder.Confirmed already that curcumin was nontoxic, had antioxidant activity, can breed by anticancer, and inflammation-inhibiting.Curcumin can suppress the generation of proinflammatory cytokine, as TNFa, and interferon gamma and IL-6, described cytokine is by the macrophage and the T emiocytosis that activate during inflammatory reaction.The curcumin mechanism of action comprises, suppresses important Cellular Signaling Transduction Mediated approach, and described approach participates in cancerous cell and by NFkappaB, COX, oxygenase (LOX), and the inflammatory reaction of derivable nitricoxide synthase (iNOS) mediation.Curcumin can reduce in the carcinogenesis stage the abnormal rise of COX and/or iNOS, and can also suppress to participate in the interior composition of key cells of cancer cell multiplication.Already observed curcumin and prevented and/or treated significantly effect on the animal model of the various diseases that comprises cancer.Because it does not have obvious toxicity, curcumin is increased (in August, 2009) recently to FDA's GRAS(Generally Regarded As Safe) in catalogue.The every day of recommending, maximum safe dose was confirmed as 1.75 grams for each person every day.
The curcumin of taking in shows low blood plasma and organizes level, and this is because of malabsorption to a great extent, and tachymetabolism (referring to Fig. 1) and rapid system are eliminated (Anand et al.Molecular Pharmaceutics Vol.4, No.6; 2007) reason.In order to improve the bioavailability of curcumin, already taked several different methods.These methods comprise the use adjuvant, as disturbing the piperine of sugar ester reaction; Use the method for liposome or particle transport; Use the curcumin phosphatide complexes; And use the curcumin analog (for example, EF-24).
Fig. 4 a-c represents to be blended in based on (Fig. 4 a), (Fig. 4 b) the SLP-curcumin granule that is dispersed in water, and the curcumin crystal (Fig. 4 c) that obtains by mixing curcumin powder and water in the carrier of Mel.
Di indolyl methane (DIM)
DIM is a kind of brassica plant that comes from, as Caulis et Folium Brassicae capitatae, and Brassica oleracea L. var. botrytis L., the bioactivator of brussels sprout and Broccoli.The result of some researchs shows, DIM shows promising protective effect on cancer risk, particularly prevents mammary neoplasms (breast carcinoma).Taking DIM with the single dose form to the rat oral intubation before carcinogen is processed makes sickness rate and multiplicity by the mammary neoplasms of dimethylbenzanthracene-induce reduce 70-80%(Wattenberg et al., Cancer Res., 38, (1978) 1410-1413).In addition, repeat again oral DIM in the developmental stage of the mammary neoplasms morbidity of dimethylbenzanthracene-induce, can suppress tumor growth up to 95%(Chen et al., Carcinogenesis19(1998 in rodent), pp.1631-1639).
DIM also is widely used as the papillomatous complementary therapy of recurrent respiratory (Auborn et al., the Antivir.Ther.7(2002) 1-9. that caused by the human papilloma virus of some type (HPVs)).
The anti-tumor activity of DIM may be undertaken by regulating immunoreation.Research had confirmed to contact DIM already can affect main immunoreation, comprises the activity of natural killer cell, and antibody produces and the cell-mediated immunity of T-.Importantly, DIM can raise the expression of interferon (IFN)-γ and IFN-γ receptor, and strengthens the effect that the MHC I antigen of IFN-γ-induce is expressed in breast cancer cell, makes its pairing effect T cell responsive.
IFN-γ helps to suppress former immunity and inflammatory reaction that develops with metastatic tumor, and the important regulatory factor of antiviral response.Therefore, if DIM has the immunostimulatory properties of broad sense, these abilities may help its antitumaous effect really.With it mice, DIM is proved and can induces splenocyte (B and T cell) propagation, and active oxygen (ROS) generates, and cytokine generation and viral infection resisting (Xue et al., J.Nutr.Biochem.19, (2008), 336-344).Add DIM in cultured cells, can promote splenocyte propagation and the generation of the ROS that produced by peritoneal macrophages.Be the main amboceptor of host defense due to cytokine, during immunoreation, they can regulate antigen-presenting cell, the signal transmission between lymphocyte and other host cells.The cytokine integral body that is presented on tissue site is determining the type for the host response of tumor and infection.In fact, promote the cytokine of the immunity development that T-is cell-mediated can induce or strengthen described antitumor and antimicrobic immunity.Importantly, hemopoietic growth factor, G-CSF are to induce bone marrow to generate how leukocytic cytokine, and leukocyte is that infection and anticancer institute are requisite.In a word, above data effectively show, DIM has effective immunoregulatory activity, the antitumor of this and this meals indole, and antiviral and antibacterial activity coincide.
Quercitroside (Quercetin)
Quercitroside is the flavonoid of plant derivation, and it may have antiinflammatory and antioxidant properties.Quercitroside is in antagonism or assist prophylaxis of cancer, prostatitis, and heart disease, cataract, anaphylaxis/inflammation and respiratory disorder have positive role as bronchitis and asthma.The research of 8 years is by a definite date found, three kinds of flavonol---kaempferol, Quercitroside is relevant to lower pancreas cancer risk with the existence of myricetin in people's normal diet.Confirmed that Quercitroside shows obvious anti-inflammatory activity by generation and the release that suppresses histamine and other allergy/inflammatory mediators.In addition, it can produce effective antioxidant activity and play the ascorbic effect of saving.With it mice, but oral dose is the expression of the Quercitroside splicing thread plastochondria biomarker of 12.5-25mg/kg, and has improved motion persistency.In vitro study shows, the combination of Quercitroside and resveratrol can suppress the generation of adipose cell.
Genistein/daidzin (Genistein/Diadezin)
Genistein and daidzin are to be present in to comprise lupin, Semen Viciae fabae, Semen sojae atricolor, the isoflavone in the various plants such as Herba Gelsemii Elegantis and Psoralea.Except the effect of antioxidant and anthelmintic, confirmed that a lot of isoflavone can interact with the estrogen receptor of animal and human's class, cause being similar to the effect that estrogen causes in vivo.
Have found that genistein and other isoflavone have blood vessel formation against function (blocking-up neovascularization), and can block the uncontrolled Growth of Cells relevant to cancer, and this effect is very likely to realize by the activity that suppresses the material that in body, regulating cell division and cell survive.Research is discovery also, and genistein can be used for treating leukemia, and it can be used for and other medicament for treatment of leukemia make up, to improve its curative effect.
Silymarin (Silymarin)
Silymarin (SM) is a kind of lipophilic extract of Milk Thistle (milk thistle), and is comprised of the isomer of several flavanolignan.External zooscopy shows, silibinin (main active of silymarin) is at the human benign prostatic cancerous cell, estrogen-dependency and-independence mankind mastopathy cell, the ectocervical cancerous cell of the mankind, human colon's cancerous cell, and have in the little and non-small cell lung cancer cell of the mankind and protect the liver (anti-liver poison) characteristic and antitumaous effect; For example, referring to http://en.wikipedia.org/wiki/Silibinin#cite_note-0.
Cobalamine (vitamin B 12)
Cobalamine helps Red blood corpuscle, bone marrow, the formation of carbohydrate, fat and protein metabolism, nerve and cardiovascular function, and play a role in DNA is synthetic.Lack this vitamin and can cause anemia, collapse, irritability, depression is breathed hard, difficulty in walking, the loss of memory, emotion change, disorientation, dementia and constipation.Every day, the cobalamine dosage greater than 3 milligrams can cause eye symptom.The cobalamine shortage mainly appears in the crowd with malabsorption and myelodysplastic syndrome.All the other situations of malnutrition anemia are usually relevant to cobalamine, modally relate to food-cobalamine malabsorption, and/or folic acid deficiency.The cobalamine shortage usually occurs in the patient who suffers from malabsorption, but, because its clinical manifestation is not obvious, usually is difficult for being discovered or studying.
Folic acid (Folate)
Folic acid plays an important role in nucleic acid and amino acid metabolism.Inevitably, it be keep Growth of Cells and neural normal function and grow institute requisite.Old people's folic acid deficiency is followed simultaneously following symptom, as is breathed hard take anemia as feature, and Mental fatigue is unable.Folic acid deficiency also can cause glossodynia, depression, nerve injury and baby's neural tube defect, heart disease and cacomelia.If but every daily dose of folic acid can cause anemia greater than 400 milligrams, and can cover up the symptom that cobalamine lacks.
Ferrum (Iron)
Ferrum is a lot of biological molecule, as the essential part of hemoglobin.The speed that absorption of human body derives from the ferrum of animal derives from the ferrum speed of plant faster than absorption.Iron deficiency is a kind of common sympton, and can cause such as diseases such as anemias.For the mankind, every daily dose of the ferrum of recommendation is about 10 milligrams; Normal diet can provide this quantity usually, still, suffer from malabsorption or often diarrhoea needs of patients augment.
As indicated above, compositions of the present invention can be used for treating disease or improves healthy.
Therefore, according to another aspect of the present invention, a kind of method that provides treatment to suffer from the object of disease is benefited the Nutrition that the physiological action that the curcumin that described object can provide from compositions of the present invention and/or DIM have and the food carrier is carrier of described compositions have.
An example of this disease is cancer.In treatment of cancer, described food carrier is carrier is the Mel of minimum level form processing, because it contains the natural anti-cancer compound, and can provide nutrition, and described physiologically active composition is DIM, also can contain curcumin (being the SLPs form).
Described compositions is especially suitable for use as the cancer complementary therapy.Chemotherapeutic effect is not only for cancerous cell, therefore, can cause serious side effect, as immunosuppressant and bone marrow depression disease.With it the cancer patient of the immunologic hypofunction for the treatment of with chemotherapy, DIM can alleviate the granulocytopenia of chemotherapy-induced, and immune response stimulating.In addition, due to Mel, DIM and curcumin have antiviral and antibacterial characteristic, and the cancer patient of chemotherapy treatment eats compositions of the present invention, may help to reduce the sickness rate of the virus relevant to chemotherapy and antibacterial infection.
The cancer patient can take the combination treatment of the present invention of three dosage day, and each dosage comprises 1 gram Mel, the approximately DIM of 200mg and the approximately curcumin of 400mg.
The present invention also can be due to treatment and the old and feeble disease relevant with immunosenescence.
Along with aging, immune system can experience distinctive and multifaceted variation.These variations occur in all types of leukocyte, comprise neutrophilic leukocyte, T-cell, B-cell, monocyte/macrophage, arborescent cell and natural killer cell.Therefore, aging affects congenital and acquired immunity function.Generally speaking, this process is known as " immunosenescence " (" imrnunosenescence ") and relates to along with age increases immune natural degeneration gradually.It relates to ability that the host makes a response to infection and the exploitation of permanent immunity memory, and is concrete as by inoculation.The immunodeficiency that this aging is relevant is ubiquitous, and appears in long-life and short life species, and is with their change of age, relevant to life expectancy rather than age.It is considered to be in the important factor in order that increases M ﹠ M in the old people.As if immunosenescence is not random decay, and on the contrary, it manifests a kind of reverse repetition evolutionary pattern, and is subjected to the most parameters that immunosenescence affects to be subjected to genetic control.Immunosenescence also can be regarded as inevitably contacting the continuously adjustable result of plurality of antigens such as virus and antibacterial sometimes.Immunosenescence is a kind of multiple-factor symptom, can cause problem important on Various Diseases Neo-Confucianism in old group.Change the biology of depending on the age, exhausts as hematopoietic stem cell, and phagocyte and NK total cellular score reduce, and cause the humoral immunization that immunosenescence begins to descend.
Therefore, the functional status of old and feeble and newborn lymphocytopoietic minimizing and memory cell colony has relation.It relates to frequency and seriousness such as cancer, chronic inflammatory disease and height such as autoimmune disease grade.The problem that the old people infects is that they indefinite S﹠S often occurs.Finally, this has caused the consequently problem for the treatment of aspect of diagnosis.
Anemia is very general in comprising the old people colony of individuality in being in long term care facilities and old specialized hospital.Importantly, even anemia is also relevant to disadvantageous health effect.Therefore, the relation of anemia and health care is very large.In the old people, the modal etiology of anemia is chronic disease/inflammation; Ferrum, folic acid and vitamin B 12The anemia that (cobalamine) causes.
Such as the old people, in the colonies such as underfed people, comprise Mel, the compositions of DIM and vitamin can be used for treatment virus and antibacterial infects, and anemia.Described Mel and DIM can provide antibacterium and antiviral functions, and DIM can strengthen the hematopoietic cytokine generation simultaneously.Crucial vitamin can promote blood to generate as cobalamine and folic acid.
Treatment can comprise five dosage every day of a kind of compositions, and said composition comprises 1g Mel, 200mg DIM, 50 μ g cobalamine, 20 μ g folic acid and 3mg ferrum.
The present invention also can be used for treatment such as celiac disease (CD), the diseases such as non-abdominal cavity Wheat Gluten responsive (NCGS) and irritable bowel syndrome (IBS).
Celiac disease is immune-mediated enteropathy, occurs with it at hereditism's susceptible object, much carries HLA-DQ( haplotype 2 or 8 in these objects).The absorption of some albumen is mainly the Wheat Gluten from Semen Tritici aestivi, and can bring out this disease from the albuminoid of Fructus Hordei Vulgaris and rye (Secale cereale L.).1% crowd of whole colony suffers from CD.The people who suffers from CD also has one or more other food anaphylaxis reaction, and other foods may comprise lactoprotein, Semen Maydis and Semen sojae atricolor.Symptom comprises chronic diarrhea, stomachache, and abdominal colic loses weight or growth inhibited, flesh and skeletal pain, neurological involvement and fatigue.
Evidence suggests, after the contact Wheat Gluten, can trigger the immunoreation for the Wheat Gluten derived peptide that produces by transglutaminase.Conversely, the derivative Toplink of these Wheat Gluten stimulates for the immunological cross-reaction of small intestinal from the body composition.This typical autoimmune response causes inflammatory reaction at intestinal.CD can cause the atrophy of mucous membrane of small intestine chorion, follows recessive propagation.Importantly, described disease has obviously strengthened the risk of intestinal adenocarcinoma and enteric lymphoma.
Main by the cell-mediated inflammatory process of T, can cause the destruction of mucous membrane of small intestine lining structure and function, and cause malabsorption; It has destroyed health and has absorbed nutrient, mineral such as calcium and ferrum, and the ability of fatsoluble vitamin.In fact, CD can be regarded as typical malabsorption syndrome, and is the common cause of anemia.In many instances, anemia is reported as unique initial representation, or the outer CD symptom of modal intestinal.It is known CD complication that folic acid (FA) and cobalamine (vitamin B12) lack.The another kind of common nutritional anemia relevant to CD is iron deficiency.It is reported, the iron deficiency anemia appears in 46% the patient who suffers from subclinical CD.Due to vitamin D malabsorption and hypocalcemia, osteoporosis and fracture have also appearred in some CD patient.
The Wheat Gluten intolerance is the term of a broad sense, and it comprises that the Wheat Gluten of various degree is irritated.In total population 15% is Wheat Gluten allergy according to estimates, still, is positive by check in existing immunoassay and biopsy and determines only have 1% to have CD.Although it is the important tool that confirms CD that antibody serum is learned, it be not always with the typical mucosa outward appearance of CD, i.e. the chorion atrophy of small intestinal is relevant.Some has the serological patient of CD and has normal intestinal mucosa, and there is no full-blown CD symptom.But, they have the higher risk that develops into CD in the future.
Most people with Wheat Gluten allergy do not have CD.On the contrary, they have and are called as irritated (the Non Celiac Gluten Sensitivity) symptom (NCGS) of non-abdominal cavity Wheat Gluten.Have the gastrointestinal symptom that the crowd of NCGS shows and comprise, diarrhoea, flatulence, abdominal colic etc.Also have relevant to NCGS had a headache, and fatigue is sterile, miscarriage and malabsorption.It is believed that with CD patient similarly, the immunoreation with crowd of NCGS causes by Wheat Gluten, but can not cause intestinal destroy and reinvent.A studies show that of delivering recently, even without full-blown CD, Wheat Gluten also can be induced the symptom that is similar to irritable bowel syndrome (IBS).This hypothesis of researching and proposing is, provides two trigger points after the irritated and epidemic infection IBS of Wheat Gluten, the pedigree that this at least can partial interpretation formation IBS.
IBS affects the Western countries crowd's 5-20%.This impact may be relevant to the following fact on a large scale: indefinite indigestion symptom is obscured mutually with the symptom of IBS sometimes.Importantly, IBS is second largest reason absent from duty.The probability that the women suffers from IBS is higher 4 times than the male.The symptom of IBS comprises bowel dysfunction, swelling, stomachache, spasm, diarrhoea and constipation.Known anxiety and other psychological factor meetings described syndromic degree of aggravation and frequency.
The principal character of IBS is the stool abevacuation, and, according to the observation to scrambling IBS is divided into two types: IBS-D(diarrhoea) and the IBS-C(constipation).According to estimates, because existing prescription drug lacks effectiveness, make in all IBS patients about 50% then use non-traditional medicine.
Up-to-date science data show, inflammation plays an important role in the pathophysiology of IBS.IBS patient has the proinflammatory cytokine IL-6 level of obvious rising in its blood circulation, and the expression of very high cyclo-oxygenase (COX) ring-type metabolite PGE2, known it produce by inflammatory stimulus.Evidence also shows, described inflammatory reaction is the result of immune activation.To described symptom, the hypothesis that existing research work proposes is, central nervous system is unified and had contact between the immune activation of unknown etiology, their interactions and cause gastrointestinal tract inflammation.
At present, be to use without the Wheat Gluten diet all the life to CD and the unique effective treatment of NCGS.There is not the medicine that can prevent the infringement that Wheat Gluten infringement or epidemic prevention/inflammatory system causes because of Wheat Gluten invasion and attack gastrointestinal.Except refractory without Wheat Gluten diet CD patient, to strictly adhere to making intestinal recovery from illness without the Wheat Gluten diet, cause in most of the cases eliminating all symptoms.In addition, depend on to begin edible quick degree without the Wheat Gluten diet, can reduce the higher risk of osteoporosis and intestinal cancer development.In a lot of countries, can buy without the Wheat Gluten product with doctor's prescription, and compensate by health insurance plan.But, this diet may be loaded down with trivial details; Do not observe described diet and can cause serious symptomatic recurrence.Compare with the food that contains Wheat Gluten, usually more expensive without the Wheat Gluten product, and more be difficult to seek.In the U.S., be worth without the overall market in Wheat Gluten product every year and be $ 2,000,000,000.
CD, the common pathophysiology performance of NCGS and IBS is enteritis.Therefore, contain food carrier is carrier and contain the compositions of mixing the curcumin in the solid lipid granule and can be used for treating this disease.Curcumin can Immunosuppression the activation of stimulation dependency and promoting immunity/inflammatory cytokine of cell generate, and don't can cause usually with use and can suppress the relevant serious side effect of anti-inflammatory agent that COX and LOX circulate.
Should be pointed out that curcumin has the chemoprophylaxis effect of the cancer development of preventing.Therefore, regular, use it can reduce the patient who suffers from CD with the Mel form, and intestinal generation adenocarcinoma and the lymphadenomatous higher risk of suffering from other patients colony of function of intestinal canal imbalance.
Treatment can comprise the compositions of three dosage every day, and said composition comprises the Mel of 1 gram and the curcumin (SLPs form) of about 400mg.
Compositions of the present invention can be placed in distributor and provide, for example squeeze bottle or paillon foil pouch or be sealed in esculent capsule (for example, gel capsule), and these capsule shells are packaged in aluminum foil gas bubble.Described distributor or packing can comprise one or more dosage units of the present composition.Described distributor or capsulation can be used subsidiary description.Described distributor or packing can also be with the logical height that be issued by managed care food production, use or the government organs of selling, and this notification table open policy mansion mechanism has ratified the compositions of correlation form and can use or for animals for the people.For example, described notice can comprise the label that obtains U.S. food and drugs administration approved.
By not being that those of ordinary skills can understand other purposes of the present invention, advantage and new feature for the embodiment that limits purpose below reading.In addition, that above disclose and each embodiment of the present invention that claims part below is claimed and aspect can search out the experiment support from the following examples.
Embodiment
Referring to following examples, they have illustrated the present invention with non-finite form together with above stated specification.
Curcumin solid lipid micronization dispersion in Mel
The solid lipid dispersion is a kind of induction system, and in this system, bioactivator dissolves or dissolves in the lipid that heat is melted, and described lipid at room temperature solidifies.Described heat fusing thing and water-bearing media emulsifying, and be cooled to room temperature, in order to be solidified into the granule that comprises bioactivator in its core.
Curcumin has been checked in this research---and whether a kind of polyphenolic substance that comes from diet flavoring agent Rhizoma Curcumae Longae can enough solid lipid dispersion technologies be emulsified in carrier based on Mel.
In order to optimize described solid lipid emulsion and to improve the ability that it carries curcumin, the inventor has carried out some pre-design researchs, comprises following content:
(i) dissolubility of check curcumin in various oil;
(ii) be designed for the solid lipid formulation media of the curcumin that is dispersed in Mel;
(iii) check formula property, comprise denseness and organoleptic effects, taste and odor property; With
(iv) check the physics and chemistry stability of formula by test method(s).
The composition general list that is used for this research is provided in table 1 below.
Table 1: material
Figure GDA00003069248400231
Example 1
The curcumin dissolubility
Curcumin is water insoluble, has therefore tested its dissolubility in various solvents.The curcumin dissolubility is measured by the following method: violent mixing 400mg curcumin in the 2g test solvent, and sample is heated to 90 ° of C.With the sample cool to room temperature, naked eyes detect and record dissolubility.Following table 2 provides described solubility studies result.Curcumin shows limited or relatively poor dissolubility in the oils of test, but dissolves in Polyethylene Glycol (PEG).
Table 2: curcumin dissolubility
Figure GDA00003069248400232
Figure GDA00003069248400241
In order further to test the curcumin dissolubility, build a dissolubility matrix (table 3).Check the dissolubility of curcumin in various liquid mixtures, then in Mel, described mixture has been carried out homogenize.
Table 3: curcumin dissolubility matrix
? CUR1 CUR2 CUR3 CUR4 CUR5 CUR6 CUR7 CUR8
? W/W W/W W/W W/W W/W W/W W/W W/W
Curcumin 33.33 33.33 33.33 33.33 33.33 33.33 33.33 33.33
Castor oil hydrogenated 33.33 ? ? ? ? 33.33 ? ?
The caprylic/capric triglyceride ? 33.33 33.33 ? ? ? 33.33 ?
Cortex cocois radicis glyceride ? ? ? 33.33 33.33 ? ? 33.33
The PEG100 stearate 33.33 33.33 ? 33.33 ? ? ? ?
Sucrose ester 1815 ? ? 33.33 ? 33.33 ? ? ?
Polysorbate80 ? ? ? ? ? 33.33 33.33 33.33
Amount to 99.99 99.99 99.99 99.99 99.99 99.99 99.99 99.99
Mixing temperature 100.00 100.00 100.00 100.00 100.00 100.00 100.00 100.00
Dissolubility Part Nothing Nothing Part Nothing Part Part Part
Crystallization In SLN be Be Be Be Be Be Be Be
State Solid Biphase Semi-solid Solid Solid Solid Biphase Semi-solid
Utilize the dissolubility matrix of table 3, the inventor find the dissolubility of curcumin or partial solubility relevant to the existence of PEG, therefore, PEG helps curcumin dissolving.The curcumin that is present in the castor oil hydrogenated (Cutina HR) that is mixed with the PEG-100 stearate is looked in micro-sight, and this curcumin forms solid lipid.Then select this assembly as the initial fat phase of curcumin-Mel preparation.
Example 2
The exploitation of the solid lipid curcumin preparation in Mel
Developed ' emulsifying of heat fusing thing ' method, and tested for the preparation that can finely be dispersed in the superfine micronization SLP in Mel.Scheme is optimized, so that the curcumin that SLPs carries secretly maximization, and the precipitation and the crystallization that are dispersed in the free curcumin in Mel are minimized.In addition, also monitored the parameter relevant to taste, abnormal smells from the patient and the quality of Mel carrier.Total preparation process as shown in Figure 2.
Option A: fat phase (being dispersed in the curcumin in the castor oil hydrogenated with PEG-100 stearate) is heated to 90 ℃, and Mel is heated to 70 ℃.With the heating lipid mix mutually with Mel and with Heidolph DIAX900 homogenizer with third gear speed homogenize, until described temperature is reduced to the temperature lower than at least 20 ℃ of described emulsifying temperatures, and said preparation becomes semi-solid state.
Option b: identical with option A, but some Mel is not heated to more than 50 ℃, keeping its unique Mel characteristic, because of can be destroyed in these characteristics more than 55 ℃.With described fat heat phase to 90 ℃; Half of Mel is heated to 70 ℃, and second half is heated to 40 ℃-50 ℃.With the fat phase with heat (70 ℃) Mel mix mutually, and with Heidolph DIAX900 homogenizer with third gear speed homogenize, until temperature is reduced to lower than 60 ℃.Remaining Mel is heated to 50 ℃ subsequently, then adds, and violent mixing and/or homogenize are in described lipid-honey mixt, until said preparation reaches even simultaneously.
Range estimation detects the uniformity by the preparation of this experiment preparation, examines under a microscope check abnormal smells from the patient, taste and quality, and check physics and chemistry stability.
Table 5 has been concluded three kinds of curcumin preparations that are dispersed in Mel, CUR13,14 and 15 result.
Table 5: castor oil hydrogenated-PEG-100 stearate preparation
? CUR13 CUR14 CUR15
? W/W% W/W W/W
Curcumin 11.11 5.50 0.00
Castor oil hydrogenated 11.11 5.50 11.11
The PEG100 stearate 11.11 5.50 11.11
Hot Mel (70 ℃) 66.67 33.33 75.00
Cold Mel (40-50 ℃) 0.00 50.00 0.00
Amount to 100.00 99.83 97.22
Preparation: ? ? ?
The preparation scheme A B A
Dissolubility in oil phase Be Be Be
Fat phase temperature (option b) 100℃ 90 90
Test ZT: ? ? ?
Crystallization Less and little Less and little Few, noncrystalline
State Semi-solid Semi-solid Semi-solid
Abnormal smells from the patient Fragrant and sweet Fragrant and sweet Fragrant and sweet
Mix with water Well Well Well
Taste Fragrant and sweet Fragrant and sweet Fragrant and sweet
CUR13 and CUR15 are operational version A preparations, and CUR14 operational version B preparation.Castor oil hydrogenated is lipid base material and the PEG100 stearate is used as emulsifying agent.CUR15 is preparation in contrast, to check fat phase concentration and preparation method on the impact of granular size.Said preparation and CUR13 and CUR14 compare at microscopically.
After carrying out above test, the conclusion that the inventor draws is, the PEG-100 stearate is good stabilizing agent and curcumin solvent, but, this mixture can solidify under higher temperature (higher than 70 ℃), make it be difficult to implement described preparation program, therefore impel the inventor to seek other stabilising emulsifiers.
Table 6: lecithin preparations
Lecithin 5.698005698
Sucrose ester 1811 ?
Glyceryl monostearate 5.698005698
Hot Mel (70 ℃) 38.46153846
Cold Mel (40-50 ℃) 38.46153846
Amount to 100
Preparation: ?
The preparation scheme B
Dissolubility in oil phase Insoluble
Fat phase temperature (option b) 110
Replace the PEG-100 stearate with the PEG40 stearate (CUR17, table 7) that has than low melting point.Said preparation prepares with option A, and shows gratifying result.Because lower temperature solidifies, it is easier to process, and resulting preparation is take good stability and dissolubility as feature.It has typical Mel abnormal smells from the patient.The appearance of curcumin crystal shows on a small quantity, and described curcumin is dissolving fully.Dissolving quantity is not carried out quantitatively, still, according to estimates, remaining undissolved curcumin accounts for 1-10%.
Table 7:PEG40 stearate preparation
? CUR17
Composition %W/W
Curcumin 7.14
Castor oil hydrogenated 7.14
The PEG40 stearate 7.14
Hot Mel (70 ℃) 78.57
Cold Mel (40-50 ℃) 0.00
Amount to 100.00
Preparation: ?
The preparation scheme A
Dissolubility in oil phase Part
Homogenization temperature (option A) 80
Test ZT: ?
Crystallization On a small quantity
State Semi-solid
Abnormal smells from the patient Mel
Mix with water Poor
In preparation shown in table 8, reduced the concentration of PEG40 stearate, and PEG6000 has been added described fat phase.Said preparation prepares with option A.What result obtained is the preparation with Mel (fragrant and sweet) abnormal smells from the patient, and product has the crystal that seldom can detect and good water miscibility, and after the Mel dissolving, SLP forms uniform dispersion in water.Particle diameter is generally 0.5-5 μ m, shows that they can effectively be dispersed in gastric juice.
Table 8:PEG6000 preparation
? CUR18
Composition %W/W
Curcumin 7.14
Castor oil hydrogenated 7.14
Polyethylene glycol 6000 4.29
The PEG40 stearate 2.86
Hot Mel (70 ℃) 78.57
Cold Mel (40-50 ℃) 0.00
Amount to 100.00
Preparation: ?
The preparation scheme A
Dissolubility in oil phase Part
Homogenization temperature (option A) 80
Test ZT: ?
Crystallization On a small quantity
State Semi-solid
Abnormal smells from the patient Honey flavour
Mix with water Fine
In preparation shown in table 9, utilize option A, test as the unique stabilising emulsifier of curcumin with the sucrose ester composition.Resultingly comprising that but the preparation of trickle efflorescence solid lipid granule has relatively poor water compatibility, may be because lack hydrophilic composition, as the peg moiety of PEG stearate composition.
Table 9: sucrose ester preparation
? CUR19
Composition %W/W
Curcumin 7.14
Castor oil hydrogenated 7.14
Polyethylene glycol 6000 4.29
Sucrose ester 1811 2.86
Hot Mel (70 ℃) 78.57
Cold Mel (40-50 ℃) 0.00
Amount to 100.00
Preparation: ?
The preparation scheme A
Dissolubility in oil phase Part
Homogenization temperature (option A) 80
Test ZT: ?
Crystallization On a small quantity
State Semi-solid
Abnormal smells from the patient Honey flavour
Mix with water Nothing
CUR20 and CUR21(table 10) prepare with option A.CUR20 comprises sucrose ester and PEG40 stearate, and CUR21 comprises sucrose ester and Tween80 as surface of stability activating agent.Both all can be miscible with water well; In the CUR21 preparation, lost typical Mel abnormal smells from the patient.
Table 10: sucrose ester and PEG40 stearate or Tween80 preparation
? CUR20 CUR21
Composition %W/W %W/W
Curcumin 7.14 7.14
Castor oil hydrogenated 7.14 7.14
Polyethylene glycol 6000 4.29 4.29
The PEG40 stearate 1.00 0.00
Tween80 0.00 1.00
Sucrose ester 1811 1.00 1.00
Hot Mel (70 ℃) 78.57 78.57
Cold Mel (40-50 ℃) 0.00 0.00
Amount to 99.14 100.14
Preparation: ? ?
The preparation scheme A A
Dissolubility in oil phase Part Part
Homogenization temperature (option A) 80 80
Test ZT: ? ?
Crystallization On a small quantity On a small quantity
State Semi-solid Semi-solid
Abnormal smells from the patient Honey flavour Few than Mel
Mix with water Good Good
Granular size The 0-6 micron The 0-6 micron
CUR22 prepares with option A, and CUR22(2) prepare (table 11) with option b.The fat of two kinds of preparations is mutually identical, and comprises 0.5% sucrose ester and 1.0%PEG40 stearate.Both all can be miscible with water, and all have typical Mel abnormal smells from the patient and curcumin pleasant impression.
Table 11: the optimization of sucrose ester concentration and preparation scheme
? CUR22 CUR22（2）
Composition %W/W %W/W
Curcumin 7.14 7.14
Castor oil hydrogenated 7.14 7.14
Polyethylene glycol 6000 4.29 4.29
The PEG40 stearate 1.00 1.00
Sucrose ester 1811 0.50 0.50
Hot Mel (70 ℃) 78.57 39.20
Cold Mel (40-50 ℃) 0.00 39.20
Amount to 98.64 98.47
Preparation: ? ?
The preparation scheme A B
Dissolubility in oil phase Part Part
Homogenization temperature (option A) 80 80
Test ZT: ? ?
Crystallization Almost do not have On a small quantity
State Semi-solid Semi-solid
CUR23(table 12) with option A or B preparation.Its fat phase is identical with the CUR22 preparation, but has used 4% curcumin.What obtain is a kind of smooth semi-solid preparation, has typical Mel abnormal smells from the patient, there is no aftertaste.
Table 12:4% curcumin preparation
? CUR19
Composition %W/W
Curcumin 4.00
Castor oil hydrogenated 7.14
Polyethylene glycol 6000 4.29
The PEG40 stearate 1.00
Sucrose ester 1811 0.50
Hot Mel (70 ℃) 78.57
Cold Mel (40-50 ℃) 0.00
Amount to 95.50
Preparation: ?
The preparation scheme A
Dissolubility in oil phase Part
Homogenization temperature (option A) 70
Test ZT: ?
Crystallization Considerably less
State Semi-solid
CUR24(table 13) be to prepare as lipid solvent with the food stage stearin.CUR25(table 13) be to prepare as lipid solvent with the food stage Petiolus Trachycarpi oil.Two kinds of preparations are all with the option A preparation, and resulting preparation has homogeneous texture, and the Mel abnormal smells from the patient does not have aftertaste.The microscopic examination discovery, the solid lipid spheroidal particle has loaded curcumin, and free curcumin crystal is few.The diameter of described solid lipid spheroid is 0.5-5.0 μ m.
Table 13: palm oil stearin (as lipid solvent) preparation
? CUR24 CUR25
Composition W/W W/W
Curcumin 4.00 4.00
Stearin (Stearin) 7.00 0.00
Petiolus Trachycarpi oil (Palm oil) 0.00 7.00
Polyethylene glycol 6000 4.00 4.00
The PEG40 stearate 1.00 1.00
Sucrose ester 1811 0.50 0.50
Hot Mel (70 ℃) 83.50 83.50
Cold Mel (40-50 ℃) 0.00 0.00
Amount to 100.00 100.00
Preparation: ? ?
The preparation scheme A A
Dissolubility in oil phase Part Part
Homogenization temperature (option A) 70℃ 70℃
Test ZT: ? ?
Crystallization On a small quantity On a small quantity
State Semi-solid Semi-solid
Abnormal smells from the patient Mel Mel
CUR26 is the preparation identical with CUR24, just there is no PEG6000; CUR27 is the preparation identical with CUR25, just there is no PEG6000(table 14).The purpose for preparing these preparations is to determine whether PEG6000 is necessary curcumin solvent.Two kinds of preparations are all with the option A preparation, and all do not observe the curcumin dissolving at two kinds of fat in mutually.Described preparation is carried out microscopic examination find, spherical lipid granule is not carried curcumin secretly, and the curcumin crystal has various sizes and uncommon shape.Described preparation does not show homogeneous texture.Two kinds of preparations are all take the good mouthfeel of Mel abnormal smells from the patient as feature.
Table 14: the preparation that does not contain PEG6000
? CUR26 CUR27
Composition W/W W/W
Curcumin 4.00 4.00
Stearin (Stearin) 7.00 0.00
Petiolus Trachycarpi oil 0.00 7.00
Polyethylene glycol 6000 0.00 0.00
The PEG40 stearate 1.00 1.00
Sucrose ester 1811 0.50 0.50
Hot Mel (70 ℃) 87.50 87.50
Cold Mel (40-50 ℃) 0.00 0.00
Amount to 100.00 100.00
Preparation: ? ?
The preparation scheme A A
Dissolubility in oil phase Insoluble Insoluble
Homogenization temperature (option A) 70C 70C
Temperature when preparation finishes 55C 55C
The product uniformity Be Be
Test ZT: ? ?
Crystallization Be Be
State Semi-solid Semi-solid
Abnormal smells from the patient ? ?
Except above-mentioned specific embodiment, method of the present invention also can be used for preparing the DIM that is dispersed in Mel, genistein, daidzin or Quercitroside SLP preparation.Following table 15 provides the composition that can be used for described preparation inventory.
Table 15
Figure GDA00003069248400311
Example 3
CUR64(sees following table 16) be to use Alina TMOil (being rich in the sage oil of Ω-3) preparation.
CUR64(sees following table 16) prepare with option A, resulting preparation has homogeneous texture, and semi-solid products does not have abnormal smells from the patient, has the Mel sweet taste, there is no pleasant impression.
Table 16: use Alina TMOil (being rich in the sage oil of Ω-3) preparation
Figure GDA00003069248400321
Example 4
CUR65, CUR66 and CUR67(table 17) be respectively with Punica granatum L. oil (CUR65), American Avocado Tree oil (CUR66) and olive oil (CUR67) preparation.
CUR65, CUR66 and CUR67(table 17) with the option A preparation, obtained smooth semi-solid products, have homogeneous texture, there is no abnormal smells from the patient, pleasantly sweet, there is no pleasant impression.
In all three kinds of preparations (CUR65, CUR66 and CUR67), microscopic examination has found that a small amount of 10-25 μ m curcumin crystal and diameter are the lipid granule of 3 μ m.
Table 17: be prepared with Punica granatum L. oil (CUR65), American Avocado Tree oil (CUR66) and olive oil (CUR67)
Figure GDA00003069248400331
Example 5
CUR66-1, the composition of CUR66-2 and CUR66-3 is referring to following table 18.CUR66-1 is (the output 1kg) for preparing in accordance with the following methods:
A. curcumin is melted up to 90 ℃ together with PEG6000;
B. fat is added to described PEG-curcumin solution, and is heated with stirring to 80 ℃;
C. 90% Fructus Jujubae syrup is heated to 75 ℃; Other 10% is used to dissolve potassium sorbate preservative;
D. 10% Fructus Jujubae syrup and potassium sorbate are heated to 70 ℃, dissolving, and cool to room temperature;
E. use " Silverson L4RT emulsator sieve " this mixture of homogenize;
F. with the described fat phase of the speed homogenize of 5000rpm, slowly add the Fructus Jujubae syrup, homogenize 3min;
G. homogenization speed is down to 4000rpm, homogenize 4min, cooling in water-bath;
H. at room temperature add Mel and potassium sorbate;
I. this mixture of hand mix.
CUR66-2 is (the output 1.5kg) for preparing in accordance with the following methods:
A. curcumin is melted up to 95 ℃ together with PEG6000 and fat phase;
B. the Fructus Jujubae syrup is heated to 75 ℃;
C. 10% Fructus Jujubae syrup and potassium sorbate are heated to 70 ℃, dissolving, and cool to room temperature;
D. described Fructus Jujubae syrup is added to fat mutually in, and mix with scraper;
E. with this mixture of Silverson L4RT emulsator sieve homogenize;
F. with the described lipid of speed homogenize and the Fructus Jujubae syrup 1min of 6000rpm;
G. with the described lipid of the further homogenize of the speed of 5000rpm and Fructus Jujubae syrup 3min;
H. homogenization speed is down to 4000rpm, homogenize 4min is cooled to 56 ℃ in water-bath;
I. add Mel and potassium sorbate under room temperature;
J. this mixture of hand mix.
CUR66-3 is (the output 1.5kg) for preparing in accordance with the following methods:
A. curcumin is melted up to 90 ℃ together with PEG6000 and fat phase;
B. the Fructus Jujubae syrup is heated to 70 ℃;
C. 10% Fructus Jujubae syrup and potassium sorbate are heated to 70 ℃, dissolving, and cool to room temperature;
D. with the described fat of speed homogenize of 6000rpm about 20s mutually;
E. slowly add Fructus Jujubae syrup, homogenize 3min;
F. with the described lipid of speed homogenize and the Fructus Jujubae syrup 3min of 5000rpm;
G. homogenization speed is down to 4000rpm, homogenize 4min, cooling in water-bath;
H. at room temperature add Mel and potassium sorbate;
I. this mixture of hand mix.
Three kinds of preparations have all been prepared has sweet taste, smooth semi-solid products.
In three kinds of preparations, microscopic examination has found that a small amount of 10-25 μ m curcumin crystal and diameter are the lipid granule of 3 μ m.
All preparations have all carried out stable promotion experiment, are included at the temperature of 32 ℃ or 40 ℃ to preserve 3 months, and monitors physical stability by visual examination, analyze by HPLC and measure the chemical stability of curcumin after time started and preservation 3 months.Found that all preparations are all stable under 32 ℃, some preparation shows slight layering under 40 ℃.Illustrate that curcumin is stable, does not find detectable chemical degradation.
Table 18: with Punica granatum L. oil (CUR65), American Avocado Tree oil (CUR66) and olive oil (CUR67) preparation
Figure GDA00003069248400341
Figure GDA00003069248400351
Curcumin HPLC during beginning analyzes
1: the quantitative assay result of curcumin:
Figure GDA00003069248400352
Preserve the curcumin HPLC analysis after 3 months under 40 ℃
1: the quantitative assay result of curcumin:
Figure GDA00003069248400353
Example 6
Known curcumin namely mixes with beverage or food under its natural form, has relatively poor system effectiveness, therefore, measures with living sample the degree that preparation of the present invention improves its oral bioavailability rate.
In test, male Wistar rat is accepted the curcumin that 400mg/kg do not prepare or according to method of the present invention, curcumin is mixed with solid lipid granule (SLP) preparation by the oral cavity tube feed.Slaughter respectively rat after using 15,30,60 and 120 minutes.Utilize HPLC, detect by UV, the existence of curcumin in analysed for plasma, intestinal mucosa and liver.
Identify curcumin in blood plasma, intestinal mucosa and the liver accepted with the rat of the solid lipid granule (SLP) of curcumin preparation.Use the peak of plasma levels of curcumin after the curcumin of SLP preparation than high ten times of the curcumin of using not preparation analog values afterwards.Similarly, compare with the curcumin of not preparation, use the curcumin liver higher level of curcumin afterwards of SLP preparation.On the contrary, after the curcumin of taking in the SLP preparation gastrointestinal tract mucous middle curcumin concentration a little less than using the concentration of observing after the curcumin of not preparing.
Result shows, compares with the form of not preparation, and the system that the curcumin of SLP preparation can obviously strengthen curcumin absorbs.Said preparation is for having very high medical value but the relatively poor compound of system effectiveness provides a kind of good solution.With by name
Figure GDA00003069248400361
Another kind of product contrast, this research has emphasized that this special preparation is as the contribution of carrying preparation.
Formula be curcumin (CAS458-37-7) and curcumin phosphatide complexes basically.
Figure GDA00003069248400363
Preparation used EpiKuron TM130P, a kind of enrichment of removing oil the Powdered soybean lecithin of 30% phosphatidylcholine.
Figure GDA00003069248400364
Contain 16.89% curcuminoid composition, wherein, the 93.82%th, curcumin, curcumin and Epikuron TMThe ratio of 130P is 1:4.
Figure GDA00003069248400365
To be introduced to the market by a company that is engaged in identical clinical research, to disclose a kind of new curcumin preparation, its surcharge be by mucosal tissue enter blood flow with the absorption that strengthens curcumin (referring to Timothy H.Marczylo et al., Cancer Chemother Pharmacol, 2007,60:171-177).
By relatively two research discoveries, with use
Figure GDA00003069248400366
Result compare, use the clinical research result of SLP preparation of the present invention to show to be absorbed to enter blood plasma and liver has higher curcumin concentration.In addition, it is moderate the decline that curcumin in the present invention absorbs occurring, and sustainable be elevated to oral after 60min, and
Figure GDA00003069248400367
Disclosed Bearing performance goes out decline sharply, and it stops after being absorbed in and taking 15min.This contrast shows, the novelty of SLP preparation provided by the invention and advantage are can continue to absorb, this process can appropriateness extend to oral after 60min, therefore, for described reactive compound provides stability.Described stability makes described compound have very long activity cycle in tissue.
Relative in order to give prominence to the SLP preparation Product is in the improvement aspect absorption, and we have increased by two charts, and the variable increment of described curcumin concentration at each time point is provided.
Referring to Fig. 5 a, the rat of 400mg/kg curcumin has been accepted in its expression by the oral cavity tube feed, after using curcumin, and the function of blood plasma curcumin changes of contents and time.Solid line has represented to accept the result of rat of the curcumin of SLP preparation, and dotted line has represented to accept the not result (being expressed as C3) of the rat of the curcumin of preparation.
Referring to Fig. 5 b, the rat of 400mg/kg curcumin has been accepted in its expression by the oral cavity tube feed, after using curcumin, and the function of liver curcumin changes of contents and time.Solid line has represented to accept the result of rat of the curcumin of SLP preparation, and dotted line has represented to accept the not result (being expressed as C3) of the rat of the curcumin of preparation.
Referring to Fig. 5 c, the rat of 400mg/kg curcumin has been accepted in its expression by the oral cavity tube feed, after using curcumin, and gastrointestinal tract mucous middle curcumin changes of contents and the function of time.Solid line has represented to accept the result of rat of the curcumin of SLP preparation, and dotted line has represented to accept the not result of the rat of the curcumin of preparation (namely contrast, be expressed as C3).
Referring to Fig. 6 a, the variable increment of the blood plasma curcumin concentration of its expression when the function that uses SLP and Meriva as the time (15 minutes, 30 minutes, 60 minutes and 120 minutes).
Described SLP concentration is calculated by the following method: SLP formulation concentrations-C3(is blank) curcumin concentration.
Described Meriva concentration is calculated by the following method: Meriva formulation concentrations-C3(is blank) curcumin concentration.
Calculated the variable increment of each time point.The unit of numeral is ng/ml.
During higher than SLP/Meriva curcumin concentration, use the negative sign labelling when C3 curcumin concentration.
Referring to Fig. 6 b, the variable increment of the mucosa curcumin concentration of expression when the function that uses SLP and Meriva as the time (15 minutes, 30 minutes, 60 minutes and 120 minutes).
Described SLP concentration is calculated by the following method: SLP formulation concentrations-C3(is blank) curcumin concentration.
Described Meriva concentration is calculated by the following method: Meriva formulation concentrations-C3(is blank) curcumin concentration.
Calculated each time point the variable increment.The unit of numeral is mg/g.During higher than SLP/Meriva curcumin concentration, use the negative sign labelling when C3 curcumin concentration.
Conclusion
Develop and checked the heat fusing method of the solid lipid granule that be filled with curcumin of emulsion dispersion in Mel.By the solid lipid granule of heat fusing emulsifying preparation, relate to and select a kind of curcumin to mix method in Mel.The inventor confirmed already, and curcumin dissolves in the mixture of ethylene oxide polymer and lipid.The inventor also confirmed already, and free curcumin can form the curcumin crystal in Mel and water.
The test that some product parameters are carried out showed already, the curcumin dissolubility is the key of product quality, the preferred castor oil hydrogenated that adopts, stearin and Petiolus Trachycarpi oil are as the lipid solvent composition, because this makes the formed curcumin preparation that is dispersed in Mel there is no pleasant impression, have homogeneous texture, have the Mel abnormal smells from the patient, and nearly all curcumin all is included in the lipid particles that is suspended in the Mel base material.
Be understandable that, some feature of the present invention that for the sake of clarity discloses in different embodiments also can make up proposition in one embodiment.On the contrary, the of the present invention a plurality of features that propose for simplicity's sake and in one embodiment also can be separately or provide with the subgroup form of closing of any appropriate.
Although already described the present invention in conjunction with specific embodiments, it is to be noted, much substitute, improve and change apparent to those skilled in the art.Therefore, it is intended that the present invention include such the substituting, improve and change of all that fall into the appended claims scope, suitable scope is just determined by the explanation of the broad sense of claims.
All publications of mentioning in description, patent and patent application all in full form receive and to do this paper reference, as every a publication, patent or patent application are appointed as respectively to receive specially does this paper reference.In addition, to the quoting or assert of any list of references, should not be regarded as admitting that described document can be used as prior art of the present invention in the application.

Claims (116)

1. the preparation method of a functional food comprises:
Melt lipid solvent under the condition that has the lipophilic bioactive agent;
The lipid solvent of melting and bioactivator are heated to temperature are at least 65 ℃;
The food carrier is carrier is added in the lipid solvent and bioactivator of described thawing; With,
The lipid solvent of the described thawing of emulsifying, described bioactivator and described food carrier is carrier, until form emulsion, described emulsion comprises the lipid granule that comprises described bioactivator.
2. the method for claim 1, wherein, described lipid solvent and bioactivator with described thawing is heated to step that temperature is at least 65 ℃ and comprises one the lipid solvent of described thawing and bioactivator are heated to temperature is the step of 70 ℃-90 ℃.
3. the method for claim 1, wherein described emulsifying step is at least part of carries out simultaneously with a cooling step.
4. method as claimed in claim 3, wherein, described cooling step further comprises and temperature is cooled to the step of about 45 ℃.
5. method as claimed in claim 3, wherein, described cooling step further comprises temperature is cooled to than the emulsifying temperature step of low 20 ℃ at least.
6. the method for claim 1 before also being included in the step of melting described lipid solvent under the condition that has described bioactivator, exists under the condition of described bioactivator the heating emulsification agent to the step of temperature at least 90 ℃.
7. method as claimed in claim 6, wherein, the group that described emulsifying agent selects free PEG ester and sucrose ester to form.
8. method as claimed in claim 7, wherein, described emulsifying agent is a kind of PEG ester, selects free PEG6000 ester, the group that PEG-100 stearate and PEG40 stearate form.
9. method as described in any one in claim 1 or 3, also comprise one in the lipid solvent of described food carrier is carrier being added to described thawing and bioactivator before the step of at least a portion of the described food carrier is carrier of heating.
10. method as claimed in claim 9, wherein, the step of at least a portion of the described food carrier is carrier of described heating comprises that the first with described food carrier is carrier is heated to the first predetermined temperature, and the second portion of described food carrier is carrier is heated to the second predetermined temperature lower than described the first predetermined temperature.
11. method as claimed in claim 10, wherein, described the first predetermined temperature is at least 60 ℃, and described the second predetermined temperature is no more than 50 ℃.
12. method as claimed in claim 10, wherein, the step of described interpolation food carrier is carrier further comprises the first that adds described food carrier is carrier, and comprise a step of adding the second portion of described food carrier is carrier during emulsifying step, add described second portion step can only in the situation that the temperature of other emulsified compositions carry out lower than 60 ℃.
13. the method for claim 1 also comprises:
A part to described food carrier is carrier under the condition that potassium sorbate exists heats, until form solution;
With described solution cool to room temperature; With,
Described solution is added in the lipid phase and bioactivator of described thawing.
14. the method for claim 1, wherein described food carrier is carrier is at room temperature semi-solid.
15. the method for claim 1, wherein described food carrier is carrier is at room temperature liquid.
16. the method for claim 1, wherein described bioactivator comprises the bioactive food composition.
17. the method for claim 1, wherein, the step of melting lipid solvent under described condition there being the lipophilic bioactive agent is included in to exist melts lipid solvent under the condition that is selected from the bioactivator in the group that following material forms: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid and plant sterol.
18. the method for claim 1, wherein described food carrier is carrier selects the group that free carbohydrate syrup and polysaccharide syrup form.
19. method as claimed in claim 18, wherein, described syrup selects free Mel, the group that Fructus Jujubae syrup and maple syrup form.
20. the method for claim 1 comprises that also one allows at least a portion of described lipid be solidified into the step of granule in described food carrier is carrier.
21. method as claimed in claim 20 comprises that also one is dispersed in step in described food carrier is carrier with described uniform particles.
22. method as claimed in claim 21, wherein, the step that allows at least a portion of described lipid be solidified into granule in described food carrier is carrier further comprises allows at least a portion of described lipid be solidified into microsphere in described food carrier is carrier.
23. method as claimed in claim 22, wherein, the step that allows at least a portion of described lipid be solidified into microsphere in described food carrier is carrier comprises that further one allows at least a portion of described lipid be solidified into the step that diameter is the microsphere of 0.5 μ m-5 μ m in described food carrier is carrier.
24. method as claimed in claim 20, wherein, the step that allows described lipid be solidified into granule in described food carrier is carrier further comprises the step of a granule that allows described lipid be solidified into to select the group that free solid particle and semi-solid granule form in described food carrier is carrier.
25. method as claimed in claim 20, wherein, at least 70% of described bioactivator is combined with described granule.
26. method as claimed in claim 25, wherein, at least 80% of described bioactivator is combined with described granule.
27. method as claimed in claim 26, wherein, the 90%-95% of described bioactivator is combined with described granule.
28. the method for claim 1 comprises that also one obtains the freely step of at least a lipid solvent of the following material group that forms of choosing: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
29. the method for claim 1 also comprises a step that bioactivator is mixed with described food carrier is carrier.
30. method as claimed in claim 29, wherein, the described step that bioactivator is mixed with described food carrier is carrier further comprise one will select group that free vitamin and mineral form the bioactivator step of mixing with described food carrier is carrier.
31. method as claimed in claim 29, wherein, the described step that bioactivator is mixed with described food carrier is carrier further comprises a step that the hydrophilic bioactivator is mixed with described food carrier is carrier.
32. method as claimed in claim 31, wherein, the described step that the hydrophilic bioactivator is mixed with described food carrier is carrier comprises that further will be selected a free cobalamine, folic acid, and the hydrophilic bioactivator of the ferrous gluconate group that the forms step of mixing with described food carrier is carrier.
33. a functional food comprises the lipophilic bioactive agent, lipid, with the food carrier is carrier, wherein, described lipid is at least part of to be dispersed in described food carrier is carrier with particle form, is included in described granule and described lipophilic bioactive agent is at least part of.
34. functional food as claimed in claim 33, wherein, described granule consists of the 5%-40%(w/w of described food).
35. functional food as claimed in claim 33, wherein, described lipophilic bioactive agent is the bioactive food composition.
36. functional food as claimed in claim 33, wherein, described lipophilic bioactive agent comprises freely at least a in the following material group that forms of choosing: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid and plant sterol.
37. functional food as claimed in claim 33, wherein, described lipid choosing is the following material group that forms freely: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
38. functional food as claimed in claim 33, wherein, described food carrier is carrier is at room temperature liquid.
39. functional food as claimed in claim 33, wherein, described food carrier is carrier is at room temperature semi-solid.
40. functional food as claimed in claim 33, wherein, the group that described food carrier is carrier selects free carbohydrate syrup and polysaccharide syrup to form.
41. functional food as claimed in claim 40, wherein, described syrup selects free Mel, the group that Fructus Jujubae syrup and maple syrup form.
42. functional food as claimed in claim 33, wherein, described uniform particles is dispersed in described food carrier is carrier.
43. functional food as claimed in claim 33, wherein, described granule comprises microsphere.
44. as functional food as described in claim 43, wherein, the diameter of described microsphere is between 0.5 μ m and 5 μ m.
45. functional food as claimed in claim 33, wherein, the group that described granule selects free solid particle and semi-solid granule to form.
46. functional food as claimed in claim 33, wherein, at least 70% of described bioactivator is combined with described granule.
47. as functional food as described in claim 46, wherein, at least 80% of described bioactivator is combined with described granule.
48. as functional food as described in claim 47, wherein, the 90%-95% of described bioactivator is combined with described granule.
49. functional food, also comprise emulsifying agent as claimed in claim 33.
50. as functional food as described in claim 49, wherein, the group that described emulsifying agent selects free PEG ester and sucrose ester to form.
51. as functional food as described in claim 50, wherein, described emulsifying agent is to select free PEG ester: PEG6000 ester, the group that PEG100 stearate and PEG40 stearate form.
52. functional food as claimed in claim 33, wherein, described food carrier is carrier mixes with at least a extra bioactivator.
53. as functional food as described in claim 52, wherein, the group that described at least a extra bioactivator selects free vitamin and mineral to form.
54. as functional food as described in claim 52, wherein, described at least a extra bioactivator is the hydrophilic bioactivator.
55. as functional food as described in claim 54, wherein, described hydrophilic bioactivator is to select free cobalamine, the group that folic acid and ferrous gluconate form.
56. give and have the object that needs that the method for at least a bioactivator is provided for one kind, comprise and use a kind of functional food, described food comprises at least a lipophilic bioactive agent that the lipid granule in being dispersed in the food carrier is carrier is combined.
57. method as claimed in claim 56, wherein, the described step of using a kind of functional food comprises that is further used an a kind of step with functional food of following at least a feature:
Free curcumin is selected in described lipophilic bioactive agent, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, the group that essential fatty acid and plant sterol form; With,
The group that described food carrier is carrier selects free saccharide and polysaccharide syrup to form.
58. method as claimed in claim 56, wherein, the described step of using a kind of functional food comprises that is further used an a kind of step that comprises the functional food of emulsifying agent.
59. method as claimed in claim 58 wherein, is describedly used a kind of step that comprises the functional food of emulsifying agent and is further comprised and use a kind of functional food that comprises the emulsifying agent that selects the group that free PEG ester and sucrose ester form.
60. method as claimed in claim 56, wherein, the described step of using a kind of functional food comprises that is further used an a kind of step that comprises the functional food of at least a extra bioactivator, and described at least a extra bioactivator mixes with described food carrier is carrier.
61. method as claimed in claim 60, wherein, use and a kind ofly comprise that the step of the functional food of at least a extra bioactivator that mixes with described food carrier is carrier further comprises the step of using at least a hydrophilic bioactivator that mixes with described food carrier is carrier.
62. a method for preparing functional food comprises:
A. melt the lipid solvent that comprises bioactivator at least at the temperature of 65 ℃; With,
B. the product of emulsifying step (a) and semi-solid food products carrier is carrier are until form the emulsion that comprises the solid lipid granule; Described solid lipid granule contains described bioactivator.
63. a method for preparing functional food comprises:
A. melt the lipid solvent that comprises bioactivator at least at the temperature of 65 ℃; With,
B. emulsifying (a) and liquid food carrier is carrier are until form the emulsion that comprises the solid lipid granule; Described solid lipid granule contains described bioactivator.
64. method as described in any one in claim 62 or 63, wherein, described bioactivator is the bioactive food composition.
65. method as described in claim 64, wherein, described bioactive food composition is curcumin.
66. method as described in claim 64, wherein, described bioactive food composition is DIM.
67. method as described in any one in claim 62 or 63, wherein, described food carrier is carrier is Mel.
68. method as described in any one in claim 62 or 63, wherein, described lipid solvent comprises freely at least a in the following material group that forms of choosing: castor oil hydrogenated, stearin, Petiolus Trachycarpi oil, height-Ω-3 sage oil, Punica granatum L. oil, American Avocado Tree oil, olive oil, and combination in any.
69. method as described in any one in claim 62 or 63, wherein, described lipid solvent also comprises emulsifying agent.
70. method as described in claim 69, wherein, described emulsifying agent comprises the ester that selects in the group that free PEG ester and sucrose ester form.
71. method as described in any one in claim 62 or 63, wherein, described temperature is 70-90 ℃.
72. method as described in any one in claim 62 or 63, wherein, (b) is heated at least 65 ℃ with described foodstuff base material before in step.
73. method as described in any one in claim 62 or 63, wherein, the diameter of described solid lipid granule is the 0.5-5 micron.
74. method as described in any one in claim 62 or 63, wherein, step (b) will comprise the lipid solvent of described bioactivator and described foodstuff base material when carrying out mixture is cooled to the temperature of about 45 ℃ gradually.
75. a composition of matter comprises the food carrier is carrier, comprises Uniform Dispersion solid lipid granule and at least a bioactivator therein, wherein, at least 80% of described at least a bioactivator is combined with described solid lipid granule.
76. composition of matter as described in claim 75, wherein, described bioactivator is the bioactive food composition.
77. composition of matter as described in claim 76, wherein, described bioactive food composition is curcumin.
78. composition of matter as described in claim 76, wherein, described bioactive food composition is di indolyl methane (DIM).
79. composition of matter as described in any one in claim 75-78, wherein, described food carrier is carrier is Mel.
80. composition of matter as described in claim 75, wherein, described solid lipid granule comprises freely at least a in the following material group that forms of choosing: castor oil hydrogenated, stearin, Petiolus Trachycarpi oil, Alina TMOil, height-Ω-3 sage oil, Punica granatum L. oil, American Avocado Tree oil, olive oil, and combination in any.
81. composition of matter as described in claim 75 also comprises emulsifying agent.
82. composition of matter as described in claim 81, wherein, described emulsifying agent is PEG.
83. composition of matter as described in claim 75, wherein, the diameter of described solid lipid granule is the 0.5-5 micron.
84. method of bioactivator being provided for the object that needs, comprise and use a kind of food carrier is carrier, it comprises Uniform Dispersion solid lipid granule and at least a bioactivator therein, wherein, at least 80% of described at least a bioactivator be combined with described solid lipid granule.
85. method as described in claim 84 wherein, is used by oral and is entered.
86. a composition of matter comprises the Mel carrier, comprises Uniform Dispersion solid lipid granule therein and is clipped in curcumin and/or DIM in described grain solid lipid.
87. functional food as claimed in claim 33, wherein, described functional food can be 32 ℃ of stable preservations 3 months.
88. composition of matter as described in claim 75, wherein, described composition of matter can be 32 ℃ of stable preservations 3 months.
89. a method that improves the lipophilic bioactive agent concentration in patient body comprises:
By method claimed in claim 1, described lipophilic bioactive agent is mixed in a kind of functional food; With,
Give the described functional food that has the patient who needs to use scheduled volume.
90. method as described in claim 89, wherein, described lipophilic bioactive agent is the bioactive food composition.
91. method as described in claim 89, wherein, described lipophilic bioactive agent comprises freely at least a in the following material group that forms of choosing: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid, and plant sterol.
92. method as described in claim 89 wherein, the group that the free following material of described lipid solvent choosing forms: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
93. method as described in claim 89 also comprises a step that improves the lipophilic bioactive agent concentration in described its blood of patient that needs are arranged.
94. method as described in claim 89 also comprises a step that improves the lipophilic bioactive agent concentration in described its liver of patient that needs are arranged.
95. method as described in claim 89 also comprises the step of a lipophilic bioactive agent concentration in the gastrointestinal mucosa that improves the described patient that needs are arranged.
96. a method that improves the lipophilic bioactive agent concentration in patient body comprises:
Give the described functional food that comprises as claimed in claim 33 described lipophilic bioactive agent that has the patient who needs to use scheduled volume.
97. method as described in claim 96, wherein, described lipophilic bioactive agent is the bioactive food composition.
98. method as described in claim 96, wherein, described lipophilic bioactive agent comprises freely at least a in the following material group that forms of choosing: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid, and plant sterol.
99. method as described in claim 96, wherein, the group that the free following material of described lipid choosing forms: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
100. method as described in claim 96 also comprises a step that improves lipophilic bioactive agent concentration described in described its blood of patient that needs are arranged.
101. method as described in claim 96 also comprises a step that improves lipophilic bioactive agent concentration described in described its liver of patient that needs are arranged.
102. method as described in claim 96 also comprises a step that improves lipophilic bioactive agent concentration described in described its gastrointestinal mucosa of patient that needs are arranged.
103. the method for the disease of lipophilic bioactive agent improvement is passed through in a treatment, comprising:
By the described method of claim 1, a kind of functional food is mixed in described lipophilic bioactive agent; With,
Use the described functional food of scheduled volume for the patient who suffers from described symptom.
104. method as described in claim 103, wherein, described lipophilic bioactive agent is the bioactive food composition.
105. method as described in claim 103, wherein, described lipophilic bioactive agent comprises freely at least a in the following material group that forms of choosing: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid, and plant sterol.
106. method as described in claim 103, wherein, the group that the free following material of described lipid solvent choosing forms: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
107. method as described in claim 103, wherein, the group that the free following disease of described disease choosing forms: immunological diseases, heart disease, respiratory disorder, inflammation, cancer, leukemia, lymphoma, gastrointestinal cancer, genitourinary system carcinoma disease, breast carcinoma, ovarian cancer, the head and neck cell carcinoma, pulmonary carcinoma, melanoma, the neurological cancer, gastroenteropathy, gastric ulcer, colitis, intestinal tract disease, Crohn disease, colorectal cancer, fatty liver and non-alcoholic stellato-hepatitis (NASH), edema, arthritis, pancreatitis, oculopathy, inflammatory diseases and combination in any thereof.
108. method as described in claim 103, wherein, the group that the free following disease of described disease choosing forms: Respiratory papillomatosis, prostatitis, cataract, anaphylaxis, bronchitis, asthma, celiac disease, non-abdominal cavity Wheat Gluten sensitivity and irritable bowel syndrome.
109. the method for the disease of lipophilic bioactive agent improvement is passed through in a treatment, comprising:
Give the functional food that comprises as claimed in claim 33 described lipophilic bioactive agent that has the patient who needs to use scheduled volume.
110. method as described in claim 109, wherein, described lipophilic bioactive agent is a kind of bioactive food composition.
111. method as described in claim 109, wherein, described lipophilic bioactive agent comprises freely at least a in the following material group that forms of choosing: curcumin, di indolyl methane, Quercitroside, daidzin (diadezin), silymarin, genistein, essential fatty acid and plant sterol.
112. method as described in claim 109, wherein, the group that the free following material of described lipid solvent choosing forms: castor oil hydrogenated; Stearin; Petiolus Trachycarpi oil; Height-Ω-3 sage oil; Punica granatum L. oil; American Avocado Tree oil; Olive oil; And combination in any.
113. method as described in claim 109, wherein, the group that the free following disease of described disease choosing forms: immunological diseases, heart disease, respiratory disorder, inflammation, cancer, leukemia, lymphoma, gastrointestinal cancer, genitourinary system carcinoma disease, breast carcinoma, ovarian cancer, the head and neck cell carcinoma, pulmonary carcinoma, melanoma, the neurological cancer, gastroenteropathy, gastric ulcer, colitis, intestinal tract disease, Crohn disease, colorectal cancer, fatty liver and non-alcoholic stellato-hepatitis (NASH), edema, arthritis, pancreatitis, oculopathy, inflammatory diseases and combination in any thereof.
114. method as described in claim 109, wherein, the group that the free following disease of described disease choosing forms: Respiratory papillomatosis, prostatitis, cataract, anaphylaxis, bronchitis, asthma, celiac disease, non-abdominal cavity Wheat Gluten sensitivity and irritable bowel syndrome.
115. a method of auxiliary treatment being provided for the patient who suffers from cancer comprises:
By the described method of claim 1, a kind of functional food is mixed in described lipophilic bioactive agent; With,
In conjunction with other anticancer therapies, use the described functional food of scheduled volume for described patient.
116. a method of auxiliary treatment being provided for the patient who suffers from cancer comprises:
In conjunction with other anticancer therapies, use the functional food as claimed in claim 33 of comprising of scheduled volume of described lipophilic bioactive agent for described patient.
CN2011800498488A 2010-08-18 2011-08-18 Functional food compositions and methods Pending CN103167869A (en)

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