CN104623670A - Compositions Containing Enriched Natural Crocin and/or Crocetin, and Their Therapeutic or Nutraceutical Uses - Google Patents

Abstract

The invention relates to unique compositions containing enriched and purified natural crocin and/or crocetin for prevention and/or treatment of cancers and other conditions and diseases. Compositions comprise mainly enriched or purified natural crocin or crocetin or combination of both and possible other active phytochemicals. A composition is used as functional food, drink, dietary supplement, or therapeutic dosage to a human orally or through other appropriate way (parenteral, percutaneous, rectal, mucosal, intranasal or topical administration). A method of natural crocin and crocetin enriching and purification is revealed.

Description

A kind of compositions containing crocin and application thereof

Technical field

This subject application relates to a kind of containing enrichment or the natural crocin (crocin) of purification and/or the compositions of α-crocetin (crocetin), and to improving health and preventing or application in the compositions/medicine of Therapeutic cancer and other diseases, functional food, health product or cosmetics.

Background technology

The first cause of the world population death that cancer is.According to the data of " the global cancer fact and the data second edition " (" Global Cancer Facts & Figures 2nd Edition "), in 2008, the whole world about has 1,270 ten thousand new cancer cases to be made a definite diagnosis, and 7,600,000 people die from cancer.In book, " American Cancer Society " (American Cancer Society) estimates will there will be more than 1,600,000 new cancer cases in continental United States in 2012, and about 577,000 American dies from cancer.The year two thousand thirty, the whole world is by increase by 2,140 ten thousand new cancer cases, and 1,320 ten thousand people die from cancer.Although there are some options likely to can be used for the prevention and therapy of cancer, mostly relate to surgery operating removing tumor or cancer and surrounding tissue combined chemotherapy and radiotherapy, or get rid of operation by chemotherapy or and radiotherapy combined.New antitumor drug miscellaneous is invented, for the treatment of particular cancers.In most cases, chemotherapy is subject to serious side effect restriction and the restriction of Dose Toxicity.Chemotherapy not only produces the quality of life of serious side effects patient, also may stop the treatment of other possibility cure method.Up to the present, found not only effectively but also to be free from side effects or side effect is little as far as possible Therapeutic Method remains a huge challenge.

Increasing cancer patient adopts plant, vegetable, and medical herbs and spice and derived product thereof are as dietetic therapy or alternative medicine.In the U.S., have at least the cancer patient of half to use complementary medicine or alternative medicine, or itself and Traditional regimen such as radiotherapy and/or chemotherapy etc. are combined.From fruit, vegetable, had found in medical herbs and spice not only effectively but also do not have the medicine of adverse side effect or Therapeutic Method to be a kind of ideal methods.Its optimal situation is that a kind of product of invention can prevent various cancer and other diseases.

The present invention relates to and a kind ofly comprise the anti-cancer composition that natural crocin that is that have an enrichment or purification and α-crocetin and/or other phytochemicals composition are provided, the compositions of its uniqueness can be improved human nutrition and have therapeutical effect, prevent, alleviate and Therapeutic cancer, and prevent or treat other diseases and disease, comprise age-related diseases and neurodegenerative diseases, as Alzheimer's disease and parkinson, cardiovascular disease and cerebrovascular disease, digestive system disease, the hepatic injury that toxin and ethanol cause.These compositionss can separately for antitumor, protection normal cell, organ, or with other chemotherapeutic drug combination in serve as sensitizer, with more effectively under lower chemotherapy doses, protection normal cell and organ, kill abnormal cell.Or in methods of radiotherapy, protection normal cell and organ escape injury.

Crocin and α-crocetin are present in Stigma Croci.These chemical compositions with antioxidant activity are pigments in Stigma Croci stigma.α-crocetin is the dicarboxylic acids of the carotenoid with 20 carbon atoms, and it is the core of crocin.In general crocin comprises crocin-I (α-crocetin-two-β-D-Radix Gentianae diester), crocin-II (α-crocetin-β-D-gentiobiose-β-D-glucose ester), crocin-III (α-crocetin-mono--β-D-Radix Gentianae diester), crocin-IV (the single glucose ester of β-D-of monomethyl crocin), α-crocetin-two-(β-D-glucose) ester, α-crocetin-mono--β-D-glucose ester.Crocin mainly exists with transconfiguration, but also has a small amount of cis-structure to exist.

Below several chemical constitution, α-crocetin (α-α-crocetin):

Crocin-I (α-crocetin two-β-D-Radix Gentianae diester):

Crocin-II (α-crocetin-β-D-gentiobiose-β-D-glucityl ester):

Crocin-III (α-crocetin, single-β-D-Radix Gentianae diester):

Stigma Croci is just used to the coloring agent and the flavoring agent that make food all over the world since ancient times, also digests for strengthening, relieving cough, treatment dysmenorrhea, and treatment muscle spasm, improves emotion, anxiety of releiving, the sexual function of control depression and enhancing male.Stigma Croci is also used as healthy tonic.It is believed that, regularly absorption Flos Carthami and milk contribute to resisting common cold and asthma.In recent years, Stigma Croci is in the news and has pharmacologically active widely, comprises antioxidant activity and antitumaous effect (Abdullaev FI, 2002; Chermahini SH, 2010; Bhargavak V, 2011).

Business Stigma Croci originates in Azerbaijan, France, Greece, India, Iran, Italy, Spain, China, Israel, Morocco, and Turkey is Egyptian, Mexico.Normally dry from the Stigma Croci stigma of artificial growth.Every Stigma Croci only has three little stigmas.About needs 75000 flowers just can obtain one pound of dry Stigma Croci.At present, Stigma Croci whole world output about 300 tons, and pure picked by hand can only be leaned on.These commodity making Stigma Croci become very expensive, and supply is very limited.Stigma Croci can be relieved safe handling.Stigma Croci and extract thereof are safely used as spice, and food coloring or hyoscine are for centuries.Stigma Croci united state's grain and agricultural organization (FAO)/World Health Organization (WHO) (WHO) combination food additive Committee of Experts are decided to be food (TRS733-JECFA29/33), and be classified as generally regarded as safe material (GRAS) [citation: 21CFR182.10, on April 1st, 2012 revises] in 2012 by U.S. FDA.

Another source of crocin and α-crocetin is Fructus Gardeniae (really), Gardenia jasminoidesEllis or Gardenia augusta Merrill var.grandiflora Hort..The content of crocin in Flos Gardeniae fruit increases with fruit maturation.In the traditional medicine of China and Japan, cape jasmine fruit is used to antiinflammatory, diuresis, function of gallbladder promoting.Chinese Government ratified in 1998 and fruit of Fructus Gardeniae is listed in the list of food and medicine.In Japanese Pharmacopoeia, Fructus Gardeniae is listed in crude drug, is also listed in existing food additive (adding the bright Yoshiaki Kato of rattan justice, 2000 years).Fructus Gardeniae extract, Gardenia Yellow, is also classified as the coloring agent of INS 164 food additive by JECFA (1989).Extensively used in food dye Huang at Japanese Gardenia Yellow, as noodles, pasta, confection, beverage and curing food.Fructus Gardeniae yellow, containing the crocin almost identical with Stigma Croci and α-crocetin derivant, is crocin different with the proportion of composing of α-crocetin derivant (M.2006, Chen Y. & Zhang H.2008 for Carmona).

Research shows that Stigma Croci extract has active anticancer.Stigma Croci crude extract anticancer/antitumor performance is proved to be (Nair SC 1991,1994, Abdullaev FI.2002,2003, Chryssanthi DG.2007, Bakshi are H.2010) with external in vivo.Crocin in Stigma Croci causes dissimilar cancer cell-apoptosis.Compare the effect of tumor cell, the normal cell of In vitro culture is insensitive to crocin.Even studies have found that Stigma Croci extract can stimulate or support the growth (Abdullaev FI, 1992a, b) of human body normal lung cell.

Studies have found that the genetic damage (Premkumar K.2006) that can watch for animals the Stigma Croci water extract being rich in crocin cell causes from tumor initiator.In research, Using Comet Assay is used to compared for Stigma Croci and three famous antitumor drug: cisplatin (CIS), the genotoxic chemoproection potentiality of cyclophosphamide (CPH) and ametycin (MMC).Three doses (20,40 and 80 mgs/kg of body weight) Stigma Croci before giving antineoplastic agent, give Mouse oral five days continuously, long according to the comet tail declined, the front DNA Damage (chain interruption) significantly suppressing antineoplastic agent to be induced to cause with Stigma Croci of the DNA percentage rate display treatment in tail square and tail.

Various Delayed onset neurodegenerative diseases is considered to cause, as Alzheimer's disease and parkinson by forming poisonous amyloid structure.Human experimentation (Akhondzadeh2010) research shows that Stigma Croci has and suppresses the gathering of amyloid beta in human brain and the potentiality of deposition, and therefore Stigma Croci may be medicative to Alzheimer (AD).54 light to moderate AD patients through screening have carried out parallel double blind test in 22 weeks.Implement psychometry measure and comprise the cognitive subscale (ADAS-COG) of AD assessment scale and clinical dementia rating scale and number box to monitor the overall cognitive of patient and clinical overview.Patient is probabilistically assigned and accepts safflower capsules 30 mg/day (twice daily 15 milligrams) (A group) and donepezil Donepezil10mg/ days (twice daily 5 milligrams), has carried out the research of 22 weeks by a definite date.Result shows that Stigma Croci is effective at this dosage, and through 22 weeks to the slight treatment to moderate AD patients, result is similar in appearance to the effect of donepezil Donepezil, and donepezil group has the vomiting of remarkable frequency to experience.

As everyone knows, excessive consumption of alcohol can damage learning capacity and memory ability.Zhang (1994) is to the acute effect normal mouse of the ethanol extraction of Stigma Croci and learn to remember in addition on impaired mice to have carried out investigation and comparison.Test by experiment, Stigma Croci extract reduces the memory registration obstacle that ethanol causes, the also memory retrieval obstacle that causes of ethanol.Stigma Croci extract reduce motor-driven activity and extend by hexobarbital (Hexobarbital) cause the length of one's sleep.Stigma Croci extract is considered to the depreciation impact that can improve Mice Hepatocytes Injured by Ethanol learning and memory process, and has the effect of tranquillizing and allaying excitement.In behavior and electrophysiologic study, find (AbeK.2000), Stigma Croci extract improves the obstacle of the learning behavior that ethanol causes on mice, and prevents alcohol induced suppression hippocampal long-term from strengthening.It is a kind of activity dependent enzymes synaptic plasticity form may facilitating learning capacity and memory that hippocampal long-term strengthens.This beneficial effect of Stigma Croci extract gives the credit to crocin (Flos Carthami acid two tertiary Radix Gentianae diester), instead of α-crocetin.Someone points out, Stigma Croci extract and effective ingredient (crocin and α-crocetin) thereof contribute to treatment neurodegenerative diseases and adjoint dysmnesia.

The Stigma Croci that (Maccarone R.2008) finds in diet in zoopery can protect and be exposed to harmful light under mammiferous amphiblestroid morphology and function.The photosensitive layer crossing animal through Stigma Croci process is maintained mostly.In the animal of Stigma Croci treatment, the mortality rate of the photoreceptor cell，photosensory cell caused by lasting damaging high light greatly reduces.Stigma Croci health product are found to improve early-stage senile maculopathy (AMD) retina flicker sensitivity (Falsini B.2010).Support the effect of Stigma Croci as health product in the clinical research confirmation of Italy and Australia subsequently, and point out that crocin and α-crocetin provide lasting protection (Piccardi M.2012) for the central retina function that main active is AMD patient.

Although Stigma Croci is in the news have far-ranging pharmacologically active, comprising antioxidant activity and antitumous effect, in these main components, only crocin and Stigma Croci acid are considered to be in and produce the basic of these pharmacologically actives.Because Stigma Croci is expensive, resource is very limited, from Stigma Croci produce crocin highly enriched in a large number and α-crocetin unrealistic.And greatly, scope is from lower than 1% to 20% (Alonso GL.2001, Lechtenberg are M.2008) for the quality of Stigma Croci and wherein Stigma Croci element and α-crocetin changes of contents.The quantitative study of Stigma Croci also shows Stigma Croci market to be existed a large amount of adulterated (Lechtenberg M.2008).The α-crocetin of chemosynthesis and salt thereof are not natural, can not be equal to natural crocin and α-crocetin, and may have diverse biological nature and pharmacologically active.Fruit of Fructus Gardeniae, Fructus Gardeniae extract, or Gardenia Yellow provides viable source, can produce a large amount of high-purity crocin and/or α-crocetin to do extensive use.The crocin of lot of pure and/or α-crocetin ensure to have stable enough active component in formulation product, can effectively be applied to prevention and therapy cancer and other diseases.

Other plant compounds (organic compound from plant origin) many also have widely with various for preventing or the health-benefiting of disease therapy or cancer.Several example is provided here.Resveratrol in Fructus Vitis viniferae is studied, and report has antitumaous effect, antiinflammatory action, cardiovascular benefit, diabetes potentiality, can stamina intensifying and Kang Aercihaimoshi disease (Baur JA 2006).Curcumin chemical compounds, comprises curcumin, de-methoxy, and bisdemethoxycurcumin, is the pigment of the polyphenol in spice turmeric discovery.Curcumin is widely studied, and shows to have anticancer, antiinflammatory, antiviral, the activity (Aggarwal BB.2007) of amyloid-beta speckle in cholesterol reducing Sum decomposition brain.Tea polyphenols, comprises catechin, epicatechin, L-Epicatechin gallate, epicatechin, nutgall catechin gallic acid ester, theaflavin, theaflavin-3,3'-epicatechol gallate, TF-3-G etc., and extract is also studied.And shown health benefits widely, comprise anticancer, reduce cholesterol, antiinflammatory, defying age, anti-atherosclerosis and coronary heart disease, high blood cholesterol concentration, the effect (Mukhtar is H.2000) of hypertension.Anthocyanidin is the plant compound in the fruits and vegetables of a class, and they give the lively color of vegetable and fruit from redness to blueness.According to perhaps polyclonal, the research of animal model and human clinical trial, anthocyanidin is suggested has antiinflammatory and carcinogenesis activity, also there is angiocardiopathy preventing, obesity controlling, alleviate diabetes, with the character (He J 2010, Kalt W 2010) promoting eye health.Show with the human research that the diet being rich in anthocyanidin carries out, anthocyanidin also can prevent Parkinsonian development and improve blood pressure (J.2011, Gao X.2012 for Cassidy).

Invention before concentrates on the single crocin composition of purification mostly, no matter is crocin-1 (α-crocin) or α-crocetin.CN102516325A discloses a kind of from the method for Fructus Gardeniae production purity higher than 95% crocin.The single crocin composition of this technology concrete production purity at least 95%, crocin I (being called crocin in its invention).WO2004078695A1 discloses the purification process of α-crocetin, comprises the following steps: the hydrolysis of crocin, then purification α-crocetin.The method of the proportioning simultaneously also disclosing extracting method and change crocin and α-crocetin and the response rate improving Stigma Croci pigment.WO2010094745A1 and US2010/0210572A1 discloses a kind of method of producing Stigma Croci cellulose hydrolysate, containing a large amount of α-crocetin monoesters in its product prepared.WO2004056201A1 disclose a kind of from Stigma Croci raw material extract pigment (crocin and the α-crocetin) response rate up to 95% method, wherein the content of crocin together with α-crocetin reaches the pigment concentration of 15-24%.Crocin and salt thereof are also synthesized chemically (WO2006104610A2, US7351844B2).But these chemosynthesis α-crocetin and salt thereof are not natural, may have different biological natures and pharmacologically active.US20130156746A1 discloses a kind of dietary supplement composition, and it comprises Stigma Croci powder and resveratrol.But Stigma Croci has multiple different brackets, wherein crocin content is also Protean, is difficult to the quality of such composition product and effectiveness are consistent.US20110236481A1 discloses a kind of compositions of Stigma Croci aldehyde and/or crocin and/or Stigma Croci bitter principle containing extracting safflower plant or Stigma Croci westerly, and it can be used as satiety agent to be used for the treatment of obesity.Active component Stigma Croci aldehyde and/or crocin and/or the bitter glycosides of Stigma Croci are diluted to pole low-level (weight) in the product, and display can suppress hungry (Gout B.2010) effectively.

Apply highly purified natural crocin and/or α-crocetin in the product and can make crocin in product and/or crocin quantification, ensure the concordance of product quality.Crocin and or α-crocetin can be used alone, also can in health product other healthy and helpful plant compound composite, can also other therapeutic component composite to prevention and therapy kinds cancer and disease and improve health useful.The combination of crocin and/or α-crocetin and other plant chemical substance has good Synergistic, also has good effect for prevention and therapy cancer and disease.Emphasis of the present invention is from natural origin cape jasmine fruit, Fructus Gardeniae extract or Gardenia Yellow extract highly purified crocin and/or α-crocetin, separately or with other sanatory phytochemicals to form unique nutritional prevention compositions or pharmaceutical composition, and their purposes () prevention or treatment disease and disease comprise cancer, neurodegenerative disease, heart disease, hepatic disease, kidney disease, ocular disease, metabolism syndrome, atherosclerosis, arthritis, inflammation, obesity, diabetes etc.; (2) the liver protecting, heart, kidney, and other normal organs are avoided injury or damage; (3) improve or strengthen study/memory ability, immune system, skin health, slow down aging, and holistic health.

Summary of the invention

Stigma Croci has many health benefits, and has been used safely several thousand.But the content of the product amount of Stigma Croci and key active ingredients (crocin and α-crocetin), but very unstable.The natural crocin of enrichment of the present invention and purification and/or the object of crocin are, reduce or eliminate and there is undesirable component in Stigma Croci or cape jasmine fruit.It provide the quantity crocin consistent with effective dose and/or the compositions of α-crocetin or the product of formula, for preventing and/or treating cancer and other diseases and reinforcement and improving health status.Highly purified crocin and/or α-crocetin are particularly conducive to makes injection product.

An object of the present invention is to provide compositions for improving/strengthening the prevention of cancer, treatment and reduction risk of cancer, and improve other diseases and disease.

The present invention's object be to provide compositions for improving/strengthen/recover the cell of cancer sufferer people, tissue and organ dysfunction, life lengthening.

The present invention's object is to provide compositions for improving/strengthen the therapeutic effect of other anticarcinogen as sensitizer or reinforcing agent, reduces drug resistance.

The present invention's object is to provide compositions for improving/protecting the injury of other anticarcinogen suffered by normal cell, tissue, organ, toxin, chemotherapeutant, radiotherapy.

The present invention's object is to provide compositions and method and improves/improve the healthy and Mental Health of aging.Particularly for central nervous system to slow down, to prevent and to alleviate neurodegenerative diseases as Alzheimer's disease and parkinson.Suppress neurotoxin to produce, suppress the decomposition of acetylcholine, prevent the structure forming poisonous amyloid, cerebral function improvement, is improved quality of life.

The present invention's object is to provide compositions and method learns for improving/strengthening, memory and cognition ability; The hippocampus damage that the oxidative stress that minimizing chronic stress pressure causes causes.

The present invention's object is to provide compositions and method for improving/treating the obstacle in study, memory and cognition ability or damage that are caused by ethanol.Improve/treat the dysmnesia that neurodegenerative diseases is adjoint.

The present invention's object is to provide compositions and method and forms for the protection of/improvement/cardiac function enhancing/cardiac structure/heart; improve arrhythmia symptom and strengthen antioxidant system; prevent myocardial infarction and alleviate myocardial stunning, the recovery capability of improvement/cardiac function enhancing.

The present invention's object is to provide compositions and method for improving/strengthening the health of human body, particularly can reduce chronic inflammatory disease and prevention of inflammatory conditions, provides simple and effective, the Therapeutic Method of seldom or being substantially free from side effects.

The present invention's object is to provide compositions and method for improving/strengthening the health of human body, particularly can improve or strengthen human immune system, and having the effect of adjustment/lifting health.

The present invention's object be to provide compositions and method for improvement of/strengthen the health of human body, particularly treat and reduce serum triglycerides, T-CHOL, low density lipoprotein, LDL (LDL) cholesterol and very low density lipoprotein (VLDL) (VLDL) cholesterol levels.

The present invention's object is to provide compositions and method for improving/strengthening liver function/vigor.Particularly the liver protecting and prevent it to be subject to the damage of ethanol, toxin, metal or heavy metal; Prevent the hepar damnification that chemotherapeutics causes.Maintain and strengthen the recovery capability of liver function.

The present invention's object is to provide compositions and method for improving/improving the health of liver, and the liver especially improving/improve after hepar damnification and shock recovers, and thus, has effect of maintenance/enhancing health.

The present invention's object is to provide compositions and method for improving/strengthening renal function/kidney vigor, particularly protects kidney from damage, maintains or strengthen the recovery of renal function.

The present invention's object is to provide compositions and method for improving/strengthening eye health, slow down/preventing/treating age-related macular degeneration is sick; Increase retina and choroid and add blood flow, also promote that retinal function recovers, thus prevent the degeneration of macula ischemic retinopathies of being correlated with and aging.

The present invention's object is to provide compositions and method for improving/strengthening the health of human body, particularly diabetic disorders can be improved, suppress the glucagon toleration or insensitive caused by fat or various fatty acid or high-carbonhydrate diet, recover/maintain normal pancreatic function/state, prevent glucose toxicity.

The present invention's object is to provide compositions and method for improving/strengthening the health of human body, particularly prevents/treat fat and relevant disease disease.

The present invention's object is to provide compositions and method for improving/strengthening the health of human body, special minimizings/preventing/treating atherosclerosis, thus, has the effect of adjustment/enhancing cardiovascular health, reduction cholesterol; Preventing/treating coronary heart disease and peripheral blood vessel.

The present invention's object is to provide compositions and method for improving/improving health, particularly improves happiness, thus has calmness, prevent/improve the effect of depression.

The present invention's object is to provide compositions and method for improving/strengthening health and the skin quality of skin, particularly can improve skin aging resistance, crease-resistant, antiinflammatory, antioxidation, recovery/preventing/treating skin injury and skin aging.

An object of the present invention is to provide and bioactive ingredients can be provided direct containing the natural crocin of purification and/or the specific combination of α-crocetin, effectively prevent/treat/help cancer or tumor patient.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, and particularly formula is to increase the intake of bioactive substance.

Another object of one aspect of the invention is by composition for improved human nutrition, particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, effectively prevent/reduce the risk of cancer, treat/improve the life of cancer or tumour patient.

Another object of one aspect of the invention is to provide human nutrition and improves compositions; particularly prepare with enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin with, improve/protect by other anticarcinogen, toxin, chemotherapeutic, radiotherapy cause normal cell, tissue, organ and patient be subject to damage.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, for the patient of the neurodegenerative of preventing/treating/help, prevent/slow down/treat Alzheimer's disease and parkinson.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, with the patient of preventing/treating/help learning capacity and Impairment of Memory effectively; Improve/improve learning and memory ability.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, particularly prepare with enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, with the health of heart effectively improving/improve, treatment suffers from individuality or the subnormal state (sub-normal conditions) of heart disease.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, with inflammation-inhibiting, chronic inflammatory disease effectively, and the problem of many health that these inflammation cause.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, and particularly preparation contains enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin to improve/to improve immune system.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, to strengthen/to improve human recycle system, reduce cholesterol, triglyceride and low density lipoprotein, LDL.

Another object of one aspect of the invention is to provide human nutrition and improves compositions; particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin; to improve/to improve liver health; protect/prevent the hepatic injury/liver caused by ethanol, toxin, chemotherapeutics to damage, strengthen/recover liver function.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, effectively to improve/to improve eye health, prevent/slow down/the treatment disease relevant with aging or the individuality of subnormal situation.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, and particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, to improve and to help the life of individuality of diabetes.

Another object of one aspect of the invention is to provide human nutrition and improves compositions, particularly preparation is containing enrichment or the natural crocin of purification and/or the compounding ingredients of α-crocetin, to strengthen and to improve minimal invasive treatment's situation of coronary artery disease and peripheral vascular disease; The risk of prevention and minimizing coronary heart disease and peripheral vascular disease.

In order to realize foregoing invention object, provide following technical scheme: a kind of food/beverage/therapeutic combination/formula, wherein containing enrichment or the natural crocin of purification and/or α-crocetin.In conjunction with suitable operational version to strengthen and to remain healthy, improve subhealth state condition.

In order to realize foregoing invention object, also provide following technical scheme: a kind of therapeutic combination/formula, by containing enrichment or the natural crocin of purification, separately α-crocetin or both compositionss, be prepared from other excipient or stabilizing agent.Said composition/formula can be used for prevention or Therapeutic cancer and tumor.

In order to realize foregoing invention object, also provide following technical scheme: a kind of food/beverage/therapeutic combination, comprises the component of following uniqueness: natural concentrated crocin and α-crocetin, possible other biological active substance, protein, polypeptide and aminoacid.Immune system of its composition improves nutritious food composition, in conjunction with suitable schedule of administration, effectively can reduce the risk of the suppressed or individual immunity system exception of individual immunity system.

In order to realize foregoing invention object, also provide following technical scheme: a kind of food/beverage/therapeutic combination, comprises the component of following uniqueness: the compositions of health preserving/health care/treatment and therapeutic scheme.Naturally be rich in crocin and α-crocetin, possible other biological active substance, vitamin.The compositions of program composition uniqueness is a kind of antioxidant nutrient drug.Suitable combination/therapeutic scheme is coordinated to effectively reduce disease risks.

In order to realize foregoing invention object, also provide following technical scheme: a kind of food/beverage/therapeutic agent/topical composition comprises and is naturally rich in crocin and α-crocetin and possible other biological activating agent.Said composition is engaged into unique antioxidation nutraceutical composition.These compositionss coordinate suitable scheme, can reduce the risk done harm to by radical damage, chemical damage and light loss normal cell, tissue, organ (liver, skin etc.).

Another object of the present invention is to provide a kind of method from cape jasmine fruit, Fructus Gardeniae extract, Gardenia Yellow or Stigma Croci enrichment/purification crocin and/or α-crocetin.

The simple declaration of accompanying drawing

Fig. 1 is the flow chart described in embodiment 1 from Gardenia Yellow D500 enrichment and purification crocin.

Fig. 2 is the HPLC chromatogram of the crocin obtained in embodiment 2.

Fig. 3 is the QNMR chromatogram of the crocin obtained in embodiment 2.

Detailed Description Of The Invention

Be discussed below at embodiments of the invention about compositions although various, should be understood that, the invention provides the many applicable inventive concepts that some can embody under multiple specific background.Specific embodiment discussed in this article is only that illustrative several concrete mode manufactures and uses the present invention, not delimit the scope of the invention.

For the ease of the understanding of the present invention, as follows to some term definitions.The implication that term defined herein has usually can understand by the those of ordinary skill with related fields of the present invention.Term is as " one ", and " one " and " being somebody's turn to do " are not intended to the entity only referring to odd number, but comprise general category, and it can be used to the concrete example of explanation one class one.Term is herein for describing specific embodiment of the invention scheme, but their use does not limit the present invention, unless pointed out in the claims.

The present invention discloses a kind of nutrient drug/therapeutic combination/formula agent and/or scheme (regimens), by containing significant, the quantitative and enrichment of q.s or purification or high-purity natural crocin and/or α-crocetin, and other possible healthy and helpful phytochemicalss, and/or plant extract, and/or vitamin, and/or healthy and helpful mineral is composite forms.

The object of this invention is to provide a kind of safe natural nutrition goods/therapeutic combination for prevention, minimizing and Therapeutic cancer, old related neural decline property disease (Alzheimer's disease and parkinson), cerebral disorders, heart disease, hepatic disease, kidney disease, oculopathy, blood circulation diseases, diabetes, inflammation, skin injury, signs of skin aging and other symptoms.The invention provides safe natural dietetic product/therapeutic combination for strengthening or recover the function of brain, heart, liver, eye, kidney, pancreas and skin, and protect them from the injury of free-radical oxidation, toxin, metal, ethanol induction.The invention provides natural nutrition goods or therapeutic combination for strengthening/recovering learning and memory ability.The particular composition of the present invention by use or other effective or sanatory plant compound of crocin and/or α-crocetin or crocin and α-crocetin and possible selection, aminoacid, vitamin or the composite compositions of mineral reach prevent/improve/treat disease above-mentioned and disease.The present invention is not limited to above-mentioned disease, disease and sub-health status.These compositionss can be considered to as a kind of therapeutic agent, and also can be considered to the human nutrition improved, the Combination nova being embodied in compound botanical compound, aminoacid or vitamin is of value to the risk reducing above-mentioned disease.

Crocin and other α-crocetin glucosides (crocetin glycosides) are main color component and plant compounds in the stigma (Stigma Croci) (Crocus sativus L.) of Stigma Croci and the fruit (Fructus Gardeniae) (Gardenia jasminoides Ellis) of Fructus Gardeniae.That Stigma Croci and Fructus Gardeniae use traditionally always and be listed in food additive.From Stigma Croci or Fructus Gardeniae natural crocin, the glycosides of α-crocetin and α-crocetin is considered to safe, because large quantifier elimination finds that crocin can protect normal cell to not normal cells effect.Because the restriction of Stigma Croci source is expensive with its, taking cost into account coming business-like enrichment and purification crocin and/or α-crocetin by Stigma Croci cannot carry out.Adulteratedly also counteracts that its application making quality product in a large number on the mass change of Stigma Croci and market.The present invention is from business-like Gardenia Yellow, and Fructus Gardeniae extract or directly come enrichment and purification crocin and α-crocetin from cape jasmine fruit, providing economical and practical and high-purity crocin and/or α-crocetin, to make it apply quantitative consistent with content.Enrichment of the present invention and purification crocin and/or α-crocetin are used for nutritional supplementation or treatment product is safe, and effectively can strengthen health, prevents and reduce the risk of above-mentioned disease and disease.In the present invention, the natural crocin of enrichment and purification and/or α-crocetin is used to be marrow of the present invention in therapeutic combination or formulation product.In injectable product, particularly need crocin and/or the α-crocetin of high-purity and high-quality.

Crocin used in the present invention and/or α-crocetin are meeting under food or drug standard condition, and the crocin of enrichment or purified form and/or α-crocetin reach at least 50% content, and namely purity reaches 50%-100%.Preferably at least 80%, more preferably at least 90%, on other occasions at least 99%.Described crocin can comprise crocin-I (α-crocetin-two-β-D-Radix Gentianae diester), crocin-II (α-crocetin-β-D-gentiobiose-β-D-glucityl ester), crocin-III (α-crocetin-mono--β-D-Radix Gentianae diester), crocin-IV (β-D-mono-stearin of methyl α-crocin), α-crocetin-two-(β-D-glucityl) ester, α-crocetin-mono--β-D-glucityl ester, 13-cis-α-crocetin, the natural α-crocetin derivants being present in Stigma Croci or cape jasmine fruit such as two (β-D-gentiobiose base esters) and 13-cis-α-crocetin β-D-gentiobiose-β-D-glucityl ester.

With use compared with common Stigma Croci or Stigma Croci extract, the present invention has many advantages.Crocin and/or α-crocetin from numerous safe sources, as Gardenia Yellow, cape jasmine fruit or Fructus Gardeniae extract, can be obtained by simple method enrichment efficiently and purification.Described production process does not use toxic solvent, does not produce a large amount of refuses, is conducive to environmental conservation.Enrichment and purified crocin and/or α-crocetin purity are at least 50% ~ 99%, significantly can reduce and remove impurity component even completely, thus provide safer product.Different from the crocin that Stigma Croci extracts, crocin in described compositions and/or the content of α-crocetin, quality have superregulated property, its effective dose is used for prevention and therapy cancer, neurodegenerative disease as Alzheimer's disease and parkinson, aging-related degeneration of macula and Other diseases.Highly purified crocin described herein and/or α-crocetin are specially adapted in the compositions of injecting or infusing.

Crocin and/or α-crocetin usually detect with HPLC to analyze under the wavelength of 440nm.But if having component or composition not containing α-crocetin or carotenoid shape core texture in Stigma Croci or Fructus Gardeniae extract, these compositions or impurity can not be detected.Therefore, in order to determine the purity of crocin in Stigma Croci or Fructus Gardeniae extract, the linear concentration curve set up with the crocin standard substance of variable concentrations, and then determine that crocin purity is essential.Preferably by quantitative nuclear magnetic resonance, NMR (NMR) spectrographic method, crocin purity is measured.

Be below a method example of the present invention but the method be not limited thereto:

A. the separation and purification of crocin and/or α-crocetin:

Take 20g business Gardenia Yellow D500, be placed in centrifuge bottle, add 80% ethanol of 3 times of Gardenia Yellow weight, cover bottle, lucifuge, 35 degrees Celsius are stirred 15 ~ 20 minutes, 10000 × g centrifugal (10,000.times.g) separate supernatant after 10 minutes, collect supernatant, be placed in flask; Repeat to add dissolve with ethanol and separation of supernatant 5 times, merge supernatant, seal and be placed in-10 DEG C of refrigerator lucifuges and deposit 15 ~ 20 days, filter to isolate crystallization, with washing with acetone, obtain 5.7 grams of crocins; With this Stigma Croci element of 360 milliliter of 80% dissolve with ethanol ,-10 DEG C of recrystallization obtain purer crocin, washing with acetone, dry, obtain about 4 grams; High-purity crocin obtains by the step that column chromatography is common further, these steps comprise with in 30% ethanol dissolve before product, solution is by being filled with the chromatographic column of macroporous resin A-5, to adsorb crocin on resin, by distilled water and 30% washing with alcohol to remove impurity, with this post of 95% ethanol elution from the pure crocin of resin desorption, collect the crocin solution of eluting, concentrated and dry.The flow chart of purification crocin and/or α-crocetin as shown in Figure 1.

HPLC analyzes crocin:

Prepare linear solvent: precision takes the standard substance of 11.9 milligrams of crocin I, be placed in 10ml volumetric flask, add first alcohol and water (1:1) and dissolve crocin I, and standardize solution is to scale, in this, as mother solution.Divide and get the standard solution that mother solution makes a series of dilution.HPLC analysis is carried out to standard solution and manufactures standard curve.5 μ l of prepared solution are injected into high performance liquid chromatograph analysis.High performance liquid chromatograph is Agilent 1260/6120, Agela Venusil XBP C18 post (4.6 × 150 millimeters, 5 microns), column temperature 40 DEG C.Other conditions and gradient are listed below: mobile phase: A:4L water (using 1.5ml TFA)

B:4L acetonitrile (containing 0.75 milliliter of TFA)

Gradient:

Afterflush: 4.5min

Flow velocity: 1 ml/min

Wavelength: 440nm's

Column temperature: 40 DEG C

Corresponding HPLC peak area and the concentration of crocin I sample list in table 1:

Table 1

By calculating a linear equation y=0.3791x+18.624 (R ²=0.9994), x: be peak area, y: be concentration.Sample crocin I concentration meets linear relationship at 74.4 μ g/ml to 1190 μ g/ml scopes.

B. crystallized sample is analyzed:

Accurately take 18.8 milligrams of crystallized sample, be placed in 10ml volumetric flask, adding first alcohol and water (1:1) sample dissolution to scale obtains the ratio of the concentration of 1880 mcg/ml (18.8mg/10ml), and accurate measuring 5 milliliters is in another 10ml volumetric flask, add the first alcohol and water dilution of (1:1) ratio, obtain the sample concentration of 940 mcg/ml; The sample solution 5 μ l of preparation is injected into high performance liquid chromatography (see Fig. 2) under the condition identical with production standard linear equation analyze, by following formulae discovery sample purity:

Concentration C 2 X 100 of the concentration C 1/ crocin sample of crocin content (%)=detected solution

Measured by HPLC method, result of calculation is shown in table 2.

Table 2

C. quantitatively nuclear magnetic resonance spectroscopy (QNMR) analyzes crocin:

Accurately take in crystallized sample and maleic acid 5-10mg to NMR detector tube, add 0.6-1.0ml DMSO-d6 (>99%atom-%D) shake with sample dissolution and maleic acid.Then quantitative H-NMR analysis is carried out.Nuclear magnetic resonance analyser is Varian400MR.Measurement is set at Pulprog=zg45, d1=15, d2=19, and nt=16.δ 1.97 (12H) is selected as the peak value of quantification; δ 6.25 is interior scalar quantity peak (with reference to Fig. 3).After measurement, result passes through formulae discovery below:

Assay of sample＝[I(a) x MW(a) x N(b) x W(b) x A(b)]/[I(b) x MW(b) x N(a) x W(b)]

What QNMR detected and calculated the results are shown in table 3.

Table 3

Containing enrichment or the crocin of purification and/or the nutraceutical composition of α-crocetin or pharmaceutical composition can be used alone or form with one or more sanatory plant compounds or containing the food extract of effective dose plant compound in the present invention, plant compound comprises: acteoside, Aloearbonaside, Aloe resin B, aloin, Alpinetin, atractylodes lactone, atisine chloride atractydin, aurantio-obtusin, cimicifugol., cimifugin, cimicifugoside, gal rises fertile, ascorbic acid, astragalin, Quercetin, resveratrol, pterostilbene, curcumin, demethoxycurcumin, bisdemethoxycurcumin, theaflavin, theaflavin-3, 3'-epicatechol gallate, TF-3-G, theaflavin-3'-epicatechol gallate, L-thiamine, anthocyanidin, anthocyanin, catechin, epicatechin, nutgall catechin, epicatechin, L-Epicatechin gallate, nutgall catechin gallic acid ester, L-Epicatechin gallate, procyanidin, chlorogenic acid, cardamomin CDK1 Alpinetin chalcone., aretigenin, Arctiin, asiatic acid, asiaticoside, bergamottin, bergapton, betanin, dioscin, galangin, cimicifugoside, cinnamic acid, ferulic acid, fumaric acid, alpha-lipoic acid, carnosine, VBT (L-carnitine), caffeic acid, ellagic acid, Crataegolic acid, CAPE, CAPE, theobromine, theophylline, caffeoylquinic acids, ursolic acid, garlicin, zingiberol, shogaol, piperine, bilobalide, ginkgetin, ginsenoside, Radix Astragali saponin, Cycloastragenol, danshensu, tanshinol, the new elder brother of Radix Salviae Miltiorrhizae, TANSHINONES, Radix Salviae Miltiorrhizae diketone, rosmarinic acid, diosmin, Nobiletin, Pericarpium Citri tangerinae element, luteolin, phylloxanthin, β-lycopene, cryptoxanthin, butyl alcohol, hypericin, hyperin, Quercetin, Quercitroside, isoquercitrin, hydroxytyrosol, Luo Sailin, rosasterol, network plug is tieed up, network fine linen, Punicalagin, 4,6-(S,S)-Gallagyl-D-glucose, ampelopsin, myricetrin, kaempferol, dihydromyricetin, apigenin, naringin, naringenin, honokiol, magnolol, chimonin, mangostin, hesperetin, Hesperidin, lupeol, Indole-3-carbinol, genistein, genistin, Daidzein, daidzin, cynarin, bilobalide, bilobetin Bilobetin, epimedin, sulforaphen, phloretin, phloretin-primaverose, phlorhizin, oligomeric proanthocyanidin, PB1, procyanidin B 2, PC1, silibinin, rutin, wogonin, morin, Morusin, Mulberroside A, mulberry skin glucoside B, glycyrrhizic acid, enoxolone, linarin, protodioscin, former Gracillin, Neosynephrine, Lay bud enlightening glycosides A, stevioside, vitexin, Saponaretin, vitexin-4, vitexin-4 "-O-glucoside, apigenin-8-C-glucoside-2 "-O-rhamnoside, apigenin-8-C-glucoside-4'-rhamnoside, alpha-tocopherol, betatocopherol, Gamma-Tocopherol, Delta-Tocopherol, Deng.

The food extract including the plant compound of effective amount is selected from one of following, but be not limited to following resource: Pericarpium Citri tangerinae (bilberry), blue berry, cranberry, Fructus Rubi, Fructus Pruni pseudocerasi, Fructus Mori, Punica granatum L., purple corn, Fructus Fragariae Ananssae, Fructus Vitis viniferae, blackberry, gooseberry, black currant, Fructus Vitis viniferae, cacao bean, coffee bean, Cortex Pini, Elettaria cardamomum (L.) Maton, Cortex Cinnamomi, Radix Ginseng, the Radix Astragali, Radix Rhodiolae, Resina garciniae, Rhizoma Zingiberis Recens, Semen Ginkgo, cedra fruits, Pericarpium Vitis viniferae, Semen Vitis viniferae, Fructus Crataegi, Carlina acaulis, Brassica oleracea L. var. botrytis L., broccoli seed, Fructus Mali pumilae, Fructus Canarii albi, orange, Fructus Citri Limoniae, Fructus Capsici, Fructus Piperis, Semen sojae atricolor, Fructus Mangifera Indicae, Folium Camelliae sinensis, Fructus Lycopersici esculenti, Rhizoma Curcumae Longae, Caulis et Folium Brassicae capitatae, purple corn, fructus zizaniae caduciflorae, bitter Fructus Citri Limoniae, Folium Stevlae Rebaudianae, arhat, Fructus Lycii (Fructus Lycii), Fructus Hippophae, Radix Puerariae, Flos Caryophylli, fiber crops, Semen Cassiae, southern magnolia, Semen Myristicae, Fructus Jujubae, Flos Lonicerae, Poria, Radix Platycodonis, Semen Nelumbinis, Folium Perillae, Semen Sesami, Radix Angelicae Sinensis, Rhizoma Cimicifugae, Herba Epimedii, Fructus Schisandrae Chinensis, Radix Salviae Miltiorrhizae, Radix Glycyrrhizae, Fructus Ligustri Lucidi, Radix Ophiopogonis, Aloe, Semen Cuscutae, Semen Trigonellae, Herba Centellae, Herba Portulacae, Fructus Tribuli, etc., said components should have the level of effectively purity individually in the present compositions.Doses level can be normalized to according to purity and these components of consumption.

Nutraceutical composition in the present invention or pharmaceutical composition may further include one or more free amino acids or polypeptide class, such as arginine, lysine, methionine, histidine; leucine, isoleucine, alanine, phenylalanine, asparagine; aspartic acid, tryptophan, proline, threonine, cysteine; selenocysteine, serine, taurine, tyrosine; valine, glycine, glutamine, glutamic acid; ornithine, carnosine, VBT, glutathion.

Nutraceutical composition or pharmaceutical composition may further include one or more vitamin or mineral, include but not limited to following, vitamin A, vitamin C, vitamin B1, vitamin B2, vitamin 33, vitamin B6, vitamin B12, vitamin D, vitamin E, vitamin K (and derivant), calcium, sodium, potassium, chromium, vanadium, magnesium, manganese, selenium, copper, molybdenum, boron, vanadium, and/or ferrum (and derivant) (preferably more than dietary recommendations continued consumption RDA).

Nutraceutical composition of the present invention or pharmaceutical composition can adopt any suitable approach to give, and include but not limited to oral, parenteral (intravenous, intramuscular, intraperitoneal, in breastbone, subcutaneous, IA injection and infusion), percutaneous, rectum, mucosa, intranasal or local (percutaneous, as passed through powder, ointment, ointment, spray, drop or paster) administration.Ophthalmic preparation, ear drop, solution, and ophthalmic ointment also covered within scope of the present invention.Most suitable approach can depend on situation and the disease of receiver.

More than one dosage is applied to human body (such as, two or more dosage is interval use within a certain period of time, and every dose contains crocin and the α-crocetin of effective dose) containing effective dose crocin and α-crocetin in certain embodiments.The crocin of effective dose and α-crocetin can with the active component of one or more plant compounds and or aminoacid or polypeptide form compositions.

Also the nutrient substance of one or more carbohydrates is comprised in the compositions of some embodiments.Such as, the nutrient of carbohydrate can be selected from the group comprising the following: rice oligosaccharide ID, amylase, amylopectin, glucose, sucrose, fructose; Maltodextrin, maltose, isomaltulose, leukonid two, trehalose, ribose, trehalose.

Nutraceutical composition or pharmaceutical composition are used for the application of oral administration and dosage form can be liquid, beverage, tablet, soft capsule, capsule, pill, lozenge, chewing gum, dragee, granule, powder, or effervescent tablet, spray or functional food.

For the Solid nutritional pharmaceutical composition of oral administration or pharmaceutical composition except above-mentioned enumerate composition or compound except optionally comprise: carrier material, as corn starch, arabic gum, gelatin, Fructus Hordei Germinatus, tragakanta, microcrystalline Cellulose, Kaolin, dicalcium phosphate, calcium carbonate, sodium chloride, alginic acid, lactose, glucose, sucrose etc.; Disintegrating agent comprises, cellulose, microcrystalline Cellulose, alginic acid, etc.; Binding agent comprises arabic gum, methylcellulose, ethyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc.; With lubricant as magnesium stearate, stearic acid, polysiloxane fluid, Talcum, oil, wax, colloidal silica etc.Except active component, a kind of compositions of effervescent tablet can comprise mixed acid (as citric acid, tartaric acid, malic acid and fumaric acid, or their combination) and be dissolved in water release the carbonate of carbon dioxide as sodium carbonate, potassium bicarbonate or potassium carbonate, and water-soluble binder (starch, natural gum, cellulose gum, microcrystalline Cellulose, methylcellulose, cellulose ether, ethyl cellulose, sodium carboxymethyl cellulose, gelatin, glucose, lactose, sucrose, Sorbitol, mannitol, Polyethylene Glycol, polyvinylpyrrolidone, pectin, alginate, polyacrylamide, polyvinyloxoazolidones, polyvinyl alcohol and their mixing object) and lubricant (sodium benzoate, Polyethylene Glycol, L-Leu, adipic acid, and their combination).One compositions can also comprise other compositions, comprises, such as, and flavoring agent, filler, surfactant, coloring agent, and sweeting agent.The purposes of such excipient is known prior art.Described compositions optionally comprises coating outside one or more compositionss and/or controlled release coat as every mortise coating, enteric coating or affect the physical integrity of nutraceutical composition and/or the coating of outward appearance.

Make capsule, the dosage form of tablet and pill can also comprise buffer agent.The solid composite of similar type also can be used as the filler used in the soft hard-filled gelatin capsule of lactose or toffee and high molecular weight polyethylene glycol etc.

A correlating method aspect for the liquid nutritional pharmaceutical composition of oral administration can be prepared in water or other aqueous carrier.Except the composition of the nutraceutical composition enumerated above or pharmaceutical composition or compound, liquid nutritional medicine/pharmaceutical composition can comprise suspending agent as, such as, alginate, pectin, alginate jelly, carrageenin, arabic gum, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone etc.Described liquid nutritional medicine/pharmaceutical composition can be solution, Emulsion, syrup, gel, and powder or elixir, include or contain wetting agent, sweeting agent, the form of coloring agent and flavoring agent.Various liquid and powdered nutritional pharmaceutical composition are prepared by conventional method.

Describedly be used as injection and the nutraceutical composition of percutaneous dosing or pharmaceutical composition and comprise pharmaceutically useful sterile aqueous or non-aqueous solution, dispersion liquid, suspension or emulsion and for being reconstructed into aseptic injectable solution or dispersion liquid sterilized powder.Intravenously administrable may be implement crocin and α-crocetin for the most effective prevention and therapy cancer and the approach of other diseases and disease.Suitable aqueous and non-aqueous carrier, diluent, the example of solvent or excipient comprises water, ethanol, polyhydric alcohol (propylene glycol, Polyethylene Glycol, glycerol etc.), and suitable mixture, the organic ester of vegetable oil (as olive oil) and such as ethyl oleate injection.In addition, injection can contain stabilizing agent, solubilizing agent, suspending agent, emulsifying agent, soothing agent, buffer agent, antiseptic, isotonic agent, antibacterial and antifungal etc.Injectable compositions carries out sterilizing at final formulation process or aseptic preparation process.Nutraceutical composition of the present invention or pharmaceutical composition can also be formulated into aseptic solid preparation, such as, pass through lyophilization.Aseptic solid preparation can be dissolved in solvent, sterile water for injection, and injection normal saline or other sterile diluent form Injectable solution and be used for injecting at once.

Medicinal composition solution for parenteral can be general by dissolving described compound in medium, filter gained solution with sterilizing, then solution to load in bottle or ampoule or vial or suitable plastic bag and prepared by sealed vial or ampoule or bottle or bag.Also can, with cryodesiccated compositions, install in bottle by gained powder, then vacuum removing moisture be to improve stability.Parenteral suspensions can be prepared to be used as parenteral by substantially the same method; But suspension can be suspended in medium preferably by by active component, then with oxirane or analog, the sterilizing of gained suspension is obtained.In addition, surfactant, wetting agent etc. also can be added into can obtain the dispersed of active component.

Compositions for rectally selects suppository to be good.Suppository by by inventive compound and suitable nonirritant carrier as cocoa butter, Polyethylene Glycol or suppository wax are mixed with, and suppository wax is at room temperature solid but becomes liquid state under body temperature therefore to melt in the rectum and release of active compounds.

The compositions that the present invention is used for local or transdermal administration can be prepared as ointment, paste, cream, lotion, gel, powder, solution, spray, inhalant or patch.The buffer agent that the antiseptic of active component and pharmaceutically acceptable carrier and any needs maybe may require aseptically is mixed.Except active ingredient beyond the region of objective existence of the present invention, ointment, paste, ointment and gel may also have animal and plant fat, oils, wax, paraffin, starch, Tragacanth, cellulose derivative, Polyethylene Glycol, silicone, bentonite, silicic acid, Talcum and zinc oxide, or its mixture.Powder and spray also can contain lactose, Pulvis Talci, silicic acid, aluminium hydroxide, calcium silicates and polyamide powder, or the mixture of these materials outside compound in the present invention.Spray can contain conventional propellant in addition as Chlorofluorocarbons (CFCs).

Compositions of the present invention also can the form of liposome be applied.As known in the art, liposome is usually derived from phospholipid or other lipid matter.Liposome is by the single or multiple lift hydration Formation of liquid crystals disperseed in an aqueous medium.Can form any nontoxic of liposome, the upper acceptable and metabolizable lipid of physiology all can use.Can stabilizing agent be contained, antiseptic etc. outside the present composition of liposomal form active component in the present invention.Preferred lipid is phospholipid that is natural and synthesis and phosphatidylcholine (lecithin), can use separately or together.The method forming liposome is known in the art.See, such as, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y., (1976), p 33 et seq.

Crocin or α-crocetin or the two common amount are that each dosage is from about 1.0 milligrams to about 7000 milligrams in certain embodiments; every dosage prevents from about 50 milligrams to about 500mg and protects; or every dosage is from about 200mg to combining about 2000mg, or every dosage is from about 200 milligrams to 500 milligrams.Every dosage effective amount of crocin and crocin is the body weight of about 0.25 ~ 50 mg/kg human body in certain embodiments.Dosage and possible dose frequency can according to the ages of individuality, body weight and condition and change.Specifically determine dosage according to the purity of each composition with the diluent emulsifying agent added and other additive.

The present invention's preferred form is to provide the compositions of nutritional supplement.The preparation of its nutritional supplementation capsule can be used for oral with dry or solid composite as the filler soft or hard gelatine capsule of filling or plant capsule easily.The capsule oral prepared is as a part for food.Active component in an example formulations arranges part with weight and provides as follows: crocin and α-crocetin about 200 parts, green tea extract about 150 parts, curcumin about 50 parts, resveratrol about 50 parts, Radix Ginseng extract about 25 parts, alpha-lipoic acid about 15 parts, L-carnitine about 15 parts.The compositions of this formula and carrier can embody in a unit routinely and use the known method of supplementary industry to be filled to capsule or to be pressed into tablet makes unit dose.The scope about 100 milligrams to about 2000 milligrams of TDD (regardless of single or fractionated dose) every day, or be about 200mg every day to about 4000 milligrams.In some embodiments, TDD scope can from about 50 milligrams to every day about 5000 milligrams.The mixture of powders of this formula also can be used for preparing functional food.More example is provided after a while.

Another preferred form of the present invention provides a kind of therapeutic combination, and this form prepares soluble effervescent sheet by compression.Relatively conventional tablet and capsule, effervescent tablet has when taking medicine major advantage in the solution.Infiltration rate is very fast, and it is that applicable pH value is convenient to absorb that active component enters into stomach.Completely not only prevent gastric acid and active component from interacting but also reducing the discomfort of harmonization of the stomach esophagus because effervescent tablet dissolves in buffer solution.Compared with traditional application method, effervescent tablet improves the absorbtivity of active component.Because the carbon dioxide produced when effervescent tablet dissolves can change parietal cell rotate approach (paracellular pathway), the osmotic absorption of induction enhanced activity composition.Parietal cell rotates the main path that approach is the hydrophilic active agents absorbed: solutes accumulation enters the intercellular substance between epithelial cell and absorbs.By inference, the absorption that the gap between carbon dioxide expansion cell causes active component higher.Example: formula comprises: 1500 milligrams of citric acids, 800 milligrams of potassium bicarbonates, 800 milligrams of sodium bicarbonate, 160mg sodium carbonate, 250 milligrams of crocins and α-crocetin, 60 milligrams of polyethylene glycol 6000s, 50 milligrams of aspartames, 30 milligrams of flavorants.The material of this formula is mixed and be pressed into suitable size effervescent tablet.In order to available protecting and prevention, the dosage unit of this pharmaceutical formulation preferably 0.5 gram to 10 grams etc.Dosage and these individual components may reach 50% in above-mentioned change in value, and change is no more than 25% better.For object and the treatment for the treatment of, every day single dose or multiple dose just enough and effectively to patient from 1 gram to 20 grams.

In another preferred form, aseptic injectable solution can by the crocin of requirement and α-crocetin are incorporated in solvent suitable in right amount in pharmacy procedure enumerate with one or more needed for composition combine, subsequently prepared by filtration sterilization.Usually, dispersant is prepared containing basic disperse medium with from the sterile carrier of other composition needed for above-mentioned enumerating by being incorporated by reactive compound.As the preparation of the aseptic powdery preparation of aseptic parenteral solution, preferred preparation method is vacuum drying and lyophilization, obtains the powder that crocin and α-crocetin add any default composition like that from the solution after previous aseptic filtration.Injection example: the solution comprising crocin and/or α-crocetin and cyclodextrin or mannitol or Sorbitol or the maltose alcohol first prepared and obtained by purification under pharmaceutical grade condition, add the above-mentioned solution of preset vol or dosage in vial, lyophilization is to obtain powder then sealed under aseptic conditions bottle.Injection adds sterile water for injection or normal saline or 5% dextrin solution before use again to dissolve preparation.The crocin of purification and/or the dosage range of α-crocetin are every days 10 milligrams to 5000 milligrams, are preferably every day 50mg to 1000 milligram, are more preferably every day 100 milligrams to every day 500 milligrams.

External preparation of the present invention, examples of compositions: the compositions containing crocin α-crocetin and one or more component alpha-lipoic acid carnosine L-carnitine.Set up effect due to collaborative, above-mentioned composition be particularly conducive to prevent aging.Usually the alpha-lipoic acid produced by health along with the age, VBT, carnosine and their secretion decline, the loss that local uses these or related compound age at recruitment to increase.These compositions are also antioxidants.

Topical formulations comprise crocin by weight and/or α-crocetin are preferentially about 0.01% ~ 50% based on the gross weight of compositions, or preferred amount is about 0.1% ~ 7.0%.Or said preparation preferentially to comprise VBT in addition in the gross weight by weight based on compositions be about 0.01% ~ 50%, or more preferably by weight about 0.5% ~ 2.0%.Said preparation preferentially select in addition containing carnosine with the amount by weight in the gross weight of compositions for about 0.01% ~ 50%, or more preferably about 0.1% ~ 5.0%.

As a preferred embodiment of the present invention, a kind of compositions containing crocin and/or α-crocetin, comprise the following composition of percentage by weight: crocin or α-crocetin or both jointly account for 1-60%, green tea extract 1-50%, curcumin 1-40%, resveratrol 1-40%, Radix Ginseng extract 1-40%, alpha-lipoic acid 0.5-20%, and L-carnitine 0.1-20%; The percentage ratio sum of each component is 1.

As a preferred embodiment of the present invention, a kind of compositions containing crocin and/or α-crocetin, comprise the following composition with percentage by weight, citric acid 10-60%, potassium bicarbonate 5-40%, sodium bicarbonate 5-40%, 0.5-20% sodium carbonate, crocin or α-crocetin or both common 0.5-30%, Polyethylene Glycol 0.2-10%, A Si BATANG 0.1-8%, flavoring agent 0.1-5%; The percentage ratio sum of each component is 1.

As a preferred embodiment of the present invention, a kind of compositions containing crocin and/or α-crocetin, it is fluffy lyophilized products, wherein crocin or α-crocetin or both jointly account for 10%-99% (weight), and wherein said compositions only need by add water or normal saline or 5% glucose solution or 5% glucose or cyclodextrin or its combination liquid in mixing, shake and do not need machined a little, can obtain injectable solution or suspension or emulsion.

As a preferred embodiment of the present invention, compositions is made into dosage form or form below: tablet, soft gel, capsule, pill, lozenge, dragee, granule, powder, injection, can reassemble into the powder for injection of injection, or effervescent tablet, liquid, spray, functional food, chewing gum, chewing gum compositions, taffy, caramel confection, soft sweet, degradable films, the thin film of not degrading, hard sugar, liquid beverage, or beverage.

Above-mentioned composition is in pharmacy, and health product, apply in functional food and cosmetics.

Following given example, and should in office where face be understood to be restrictive in order to explain further and the present invention is described.Unless otherwise, all numbers and percentage ratio are all by weight.

The example of compositions:

Example 1

A preference of the open present composition of this example, but be not limited to this dosage administration.Under dry reduced pressure, by containing the grinding of following component fully, be mixed into mixture, then by 1000 milligrams of dosage filled capsules, produce gelatin or capsule.Amounts of components:

200 milligrams of crocins and/or α-crocetin

The green tea extract of 150 milligrams

50 milligrams of curcumins (curcumin)

50 milligrams of resveratrols (resveratrol)

25 milligrams of Radix Ginseng extracts (Panax ginseng extract)

15 milligrams of alpha-lipoic acids (.alpha.-lipoic acid), and

The L-carnitine (L-carnitine) of 10 milligrams

Taking above-mentioned capsule can anti-curing cancers and other disease effectively.Preferably, take night and morning.

Example 2

This example discloses another preference, but not as the restriction of the present composition.Tablet is prepared by following steps: by following effective ingredient and mixed with excipients, non-slurry pelletizing, grinding, and mixing, tabletting and coating obtain tablet.Compositions is containing the crocin of enrichment and purification and/or α-crocetin and other plant compound or extract, specific as follows:

200 milligrams of crocins and/or α-crocetin

The green tea extract of 200 milligrams

100 milligrams of curcumins

100 milligrams of Semen Vitis viniferae extracts

50 milligrams of Radix Ginseng extracts

50 milligrams of Radix Rhodiolae extracts

50 milligrams of Folium Ginkgo extract

Content is that the daily nutrition of 100 ~ 1000 milligrams supplements dosage and contributes to prevention and delay cancer and neurodegenerative diseases; strengthen brain and Mental Health; improve cognitive, learning and memory ability, the liver protecting, heart, lung, kidney, eye, skin, nerve and normal cell.

Example 3

This example provides the preference of compositions of the present invention, but be not limited to this dosage administration.

Under dry reduced pressure, by containing the grinding of following component fully, be mixed into mixture, then by 1000 milligrams of dosage filled capsules, produce gelatin or capsule.Amounts of components:

200 milligrams of crocins and/or α-crocetin

500 milligrams of dihydromyricetin (dihydromyricetin)

50 milligrams of resveratrols

50 milligrams of artichoke leaf extract (artichoke leaf extract)

Take above-mentioned capsule can effectively to escape injury and alcohol damaged by the liver protecting, or Hepatoma therapy and/or recover liver function, prevent and/or treat other disease and disease.Excellent takes night and morning, or takes before preferably drinking.

Example 4

This example provides the preference of compositions of the present invention, but be not limited to this dosage administration.Under dry reduced pressure, by containing the grinding of following component fully, be mixed into mixture, then by 1000 milligrams of dosage filled capsules, produce gelatin or capsule.Amounts of components:

250 milligrams of crocins and/or α-crocetin

200 milligrams of Citrus reticulata Blanco extract (90% polymethoxyflavone, Nobiletin and Pericarpium Citri tangerinae element) (90%polymethoxylated flavones, nobiletin & tangeretin)

100 milligrams of curcumins

50 milligrams of resveratrols

Taking above-mentioned capsule can effective prevention and therapy cancer and reduce the risk of cancer and Other diseases or disease, preferably respectively takes once when dining sooner or later.

Example 5

This example provides preference of the present invention, but is not limited to this compositions for eye health.Tablet is prepared by following steps: by following composition and mixed with excipients, non-slurry pelletizing, grinding, mixing, tabletting and coating.Compositions comprises as follows containing enrichment and purification crocin and/or α-crocetin and other plant compound or extract:

200 milligrams of crocins and/or α-crocetin

The lycopene (lycopene) of 200 milligrams

The beta-carotene of 100 milligrams

100 milligrams of Pericarpium Citri tangerinae (bilberry) extracts

50 milligrams of phylloxanthins

25 milligrams of cryptoxanthin (zeaxanthin)

Take this tablet formulations and effectively can prevent and treat age-related macular degenerative disease (AMD); increase retina blood circulation; protection retina and brain from toxin or light cause stress, improve and maintain vision and brain function, reducing the risk of cancer and Other diseases or disease.Preferably, respectively take once when sooner or later having dinner.

Example 6

This example provides preference of the present invention, but is not limited to this.Sterile injectable in amber vial or bottle or combined infusion thing is stored in lyophilized powder form, be prepared by following steps: quantitatively mixing 5 grams of high-purity crocins and/or α-crocetin (at least purity 98%, at least 99% is better) and 20 grams or 40 grams of phannaceutical grades of mannitol, mixture is dissolved in suitable solvent 400 milliliters or 800 ml distilled waters or water for injection, solution is by the aseptic filter membrane filtration sterilization of 0.15-0.22 micron, be dispensed in aseptic amber vial or bottle, lyophilization, sealed vial or bottle, label and obtain product after packing.When needing injection or transfusion, the water for injection or normal saline (0.7%w/w) the shake dissolving that add appropriate amount make solution again.

A: contain in injection lyophilizing bottle of can recombinating:

50 milligrams of crocins and/or α-crocetin

200 milligrams of mannitol

5 ml physiological salines (0.7%w/w)

B: comprise in transfusion lyophilizing bottle of can recombinating:

250 milligrams of crocins and/or α-crocetin

2000 milligrams of mannitol

50 ml physiological salines (0.7%w/w)

This injectable or infusion form of the present invention can effectively treat various cancer, and neurodegenerative disease is as Alzheimer's disease and parkinson, and other diseases and disease.

Example 7

This example provides the preference of compositions of the present invention, but be not limited to this dosage or dosage form.Follow these steps to prepare effervescent tablet: a. is by anhydrous citric acid and crocin and/or α-crocetin mixing.B. the citric acid solution adding 65% under stirring is granulated, and is dried to the moisture of granule subsequently at low temperatures lower than 0.15%.C., under low-humidity environment, gained granule is being mixed with anhydrous sodium bicarbonate, spice, A Si BATANG and Polyethylene Glycol (PEG) 6000.D. effervescent tablet made by tabletting, in sheeting operation by magnesium stearate as exterior lubricant to avoid sheeting operation time adhesion.The average weight of tablet is 3.85 grams, and diameter is 23 millimeters, and thickness is 3.15 ~ 3.25 millimeters.E. 10 are packaged into (re-sealable HDPE container) in the high-density polyethylene container of resealable.

An exemplary effervescence combination, comprises following content:

200 milligrams of crocins and/or α-crocetin

250 milligrams of dihydromyricetin

5700mg anhydrous citric acid

12000mg sodium bicarbonate

The polyethylene glycol 6000 (PEG6000) of 300 milligrams

The flavorant (lemon) of 200 milligrams

200mg A Si BATANG (aspartame)

Every day 1; be dissolved in 6 ounces of room temperature waters and drink; can effective the liver protecting; avoid the infringement it caused by ethanol or excessive iron element or other heavy metal ion; protection lung is from the cancer damaged or caused by cigarette or haze; cardiac function enhancing, prevention or Therapeutic cancer or Other diseases or symptom.

Example 8

This example provides preference of the present invention, but is not limited to this compositions, and this routine compositions can be applicable in Foods or drinks.Crocin and/or α-crocetin, Lay bud enlightening glycosides A (rebaudioside A), monoammonium glycyrrhizinate and erythritol, mix by 25:50:50:2875 weight ratio.Premixed powder product can load pouch/parcel, or subsidiary quantitatively little scoop directly apply in powder form in wet light-shielding container.Premixing powder can also be prepared further and be processed into fritter, and granule is contained in pouch or parcel or forms lamellar.2.5 grams of premixing powder join one and stir with after the fat-free of part and yoghurt without sugar (6 ounces), namely the sweet Yoghourt of the yellow of a exquisite appearance is obtained, it contains 25 milligrams of crocins and/or α-crocetin, and does not increase extra calorie.When drinking, by the powder/fritter/granules/tablets of 2.5 grams of diffluent premixings, join in the water/beverage/fruit juice of 8 ounces.(concrete addition can) can according to the preference of oneself and hobby adjustment local flavor by drinking person.After stirring 15 minutes with spoon, can obtain containing 25 milligrams of crocins and/or α-crocetin, and there is no extra caloric beverage.

Example: compositions comprises following composition:

100 milligrams of crocins and/or α-crocetin

200 milligrams of Lays bud enlightening glycosides A (rebaudioside A)

200 milligrams of monoammonium glycyrrhizinates (glycyrrhizic acid ammonium salt)

9500 milligrams of erythritols (erythritol)

The daily product of said composition, effectively can promote eye health and brain is healthy, and prevention or delay senile degeneration of macula, control slightly to the Alzheimer of moderate, prevents and reduces to obtain cancer and cardiopathic risk, and promoting holistic health.

Description is above intended to enable those skilled in the art implement the present invention.Not all possible for the present invention modifications and variations are described in detail, because those skilled in the art are seem apparent when reading during description of the present invention.Allly all should to be protected for modifications and variations of the present invention, wherein certainly to be comprised institute's those set forth above, and the scope of the present invention that following claim limits.Claims are intended to contain the element and step that indicate in all any layouts or sequence, and it is effective, to meet for object of the present invention, unless specialized contrary in context.

The U.S. Provisional Patent Application that cross reference proposes previously

As the U.S. Patent application of priority, require the priority of US provisional patent.Described temporary patent application: application number is 61/727,244, the applying date: on November 16th, 2012.The full content of described temporary patent application is incorporated in its priority U. S. application file by the mode quoted again.

Referenced patents:

List of references:

[1]International Agency for Research on Cancer:“Global Cancer Facts&Figures 2nd Edition”

[2]American Cancer Society:“Cancer Facts&Figures 2012”

[3]Chermahini SH,Majid FAA,Sarmidi MR,Taghizadeh E,Salehnezhad S.Impact of saffron as an anti-cancer and anti-tumor herb.African Journal of Pharmacy and Pharmacology2010,4(11):834-840.

[4]Bhargavak V.Medicinal uses and pharmacological properties of Crocus sativusLnn(Saffron).Int.J.Pharm Pharm Sci.2011,3,suppl 3:22-26.

[5]Carmona M,Zalacain A,Sanchez AM,Lovella JL,Alonso GL.Crocetin Esters,Picrocrocin and Its Related Compounds Present in Crocus sativus Stigmas and Gardenia jasminoides Fruits.Tentative Identification of Seven New Compounds by LC-ESI-MS.J.Agric.Food Chem.2006,54:973-979.

[6]Chen Y,Zhang H,Tian X,Zhao C,Cai L,Liu Y,Jia L,Yin HX,Chen C.Antioxidant potential of crocins and ethanol extracts of Gardenia jasminoides ELLIS and Crocus sativus L.:A relationship investigation between antioxidant activity and crocin contents.Food Chemistry 2008,109:484–492

[7]Nair SC,Panikkar B and Panikkar KR:Antitumor activity of saffron(Crocus sativus).Cancer Lett 1991,57:109-114.

[8]Nair SC,Varghese CD,Pannikar KR,Kurumboor SK,ParathodRK.Effects of saffron on vitamin A levels and its antitumor activity on the growth of solid tumors in mice.Int J Pharmacog 1994,32(2):105–114.

[9]Abdullaev FI,Frenkel GD.Effect of saffron on cell colony formation and cellular nucleic acid and protein synthesis.BioFactors 1992a,3(3):201–204.

[10]Abdullaev FI,Frenkel GD.The effect of saffron on intracellular DNA,RNA and protein synthesis in malignant and non-malignant human cells.BioFactors 1992b,4(1):43–45.

[11]Abdullaev FI:Cancer chemopreventive and tumoricidal properties of saffron(Crocus sativus L.).ExpBiol Med(Maywood)227(1):20-25,2002.

[12]Abdullaeva FI,Rivero′n-Negretea L,Caballero-Ortegaa H,Manuel Herna′ndeza J,

[13]Pe′rez-Lo′peza I,Pereda-Mirandab R,Espinosa-Aguirre JJ.Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron(Crocus sativus L.).Toxicology in Vitro.2003,17:1-6.

[14]Chryssanthi DG,Lamari FN,Iatrou G,Pylara A,Karamanos NK,Cordopatis P.Inhibition of breast cancer cell proliferation by style constituents of different Crocus species.Anticancer Res.2007,27(1A):357-62.

[15]Bakshi H,Sam S,Rozati R,Sultan P,Islam T,Rathore B,Lone Z,Sharma M,Triphati J,Saxena RC.DNA fragmentation and cell cycle arrest:a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line.Asian Pac J Cancer Prev.2010,11(3):675-9.

[16]Premkumar K,Thirunavukkarasu C,Abraham SK,Santhiya ST,Ramesh A.Protective effect of saffron(Crocus sativus L.)aqueous extract against genetic damage induced by anti-tumor agents in mice.Hum ExpToxicol 2006,25(2):79-84.

[17]Akhondzadeh S,Sabet MS,Harirchian MH,Togha M,Cheraghmakani H,Razeghi S,Hejazi SS,Yousefi MH,Alimardani R,Jamshidi A.A 22-week,multicenter,randomized,double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease.Psychopharmacology 2010,207(4):637-643.

[18]Zhang Y,Shoyama Y,Sugiura M,Saito H.Effects of Crocus sativus L.on the ethanol-induced impairment of passive avoidance performances in mice.Biol Pharm Bull.1994,17(2):217-21.

[19]Abe K,Saito H.Effects of saffron extract and its constituent crocin on learning behaviour and long-term potentiation.Phytother Res.2000,14(3):149-52.

[20]Maccarone R,Di Marco S,BistiS.Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina.InvestOphthalmol Vis Sci.2008,49(3):1254-61.

[21]Falsini B,Piccardi M,Minnella A,Savastano C,Capoluongo E,Fadda A,BalestrazziE,Maccarone R,Bisti S.Saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration.Invest Ophthalmol Vis Sci.2010,51:6118–6124.

[22]Piccardi M,Marangoni D,Minnella AM,Savastano MC,Valentini P,Ambrosio L,Capoluongo E,Maccarone R,Bisti S,Falsini B.A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration:sustained benefits to central retinal function.Evid Based Complement Alternat Med.2012,2012:429124.

[23]Alonso GL,Salinas MR,Garijo J,Sanchez-Fernandez MA.Composition of crocins and picocrocin from Spanish saffron.J.Food Quality.2001,24:219-233.

[24]Lechtenberg M,Schepmann D,Niehues M,Hellenbrand N,Wünsch B,Hensel A.Quality and Functionality of Saffron:Quality Control,Species Assortment and Affinity of Extract and Isolated Saffron Compounds to NMDA andσ1(Sigma-1)Receptors.Planta Med 2008；74:764–772.

[25]Baur JA,Sinclair DA.Therapeutic potential of resveratrol:the in vivo evidence.Nature Reviews Drug Discovery.2006,5:493-506.

[26]Aggarwal BB,Surh YJ,Shoshodia S.The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease.Advances in Experimental Medicine and Biology.2007,Volume 595.Published by Springer US.

[27]Mukhtar H and Ahmad N.Tea polyphenols:prevention of cancer and optimizing health1,2,3.Am J ClinNutr June 2000,71(6):1698-1702.

[28]He J,Giusti MM.Anthocyanins:Natural Colorants with Health-Promoting Properties.Food Science and Technology.2010,1:163-187.

[29]Kalt W,Hanneken A,MilburyP,Tremblay F.Recent Research on Polyphenolics in Vision and Eye Health.J.Agric.Food Chem.,2010,58(7):4001–4007.

[30]Cassidy A,O’Reilly EJ,Kay C,Sampson L,Franz M,Forman JP,Curhan G,Rimm EB.Habitual intake of flavonoid subclasses and incident hypertension in adults.Am.J.Cli.Nutri.2011,93:338-347.

[31]Gao X,Cassidy A,Schwarzschild MA,MD,Rimm EB,Ascherio A.Habitual intake of dietary flavonoids and risk of Parkinson disease.Neurology 201278(15)；1138-1145.

[32]Gouta B,Bourges C,Paineau-Dubreuil S.Satiereal,a Crocus sativus L extract,reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight,healthy women.Nutrition Research.2010,30:305-313.

Claims (10)

1. a compositions, is characterized in that, comprises at least one in crocin and α-crocetin, and described crocin and α-crocetin obtain from natural origin Extraction and enrichment or purification, also comprise at least one active skull cap components, described active skull cap components refers to plant compound or natural extract, (1) described plant compound comprises: acteoside, Aloearbonaside, Aloe resin B, aloin, Alpinetin, atractylodes lactone, atisine chloride atractydin, aurantio-obtusin, cimicifugol., cimifugin, cimicifugoside, gal rises fertile, ascorbic acid, astragalin, Quercetin, resveratrol, pterostilbene, curcumin, demethoxycurcumin, bisdemethoxycurcumin, theaflavin, theaflavin-3, 3'-epicatechol gallate, theaflavin-3-epicatechol gallate, theaflavin-3'-epicatechol gallate, L-thiamine, anthocyanidin, anthocyanin, catechin, epicatechin, nutgall catechin, epicatechin, L-Epicatechin gallate, nutgall catechin gallic acid ester, L-Epicatechin gallate, procyanidin, chlorogenic acid, cardamomin CDK1 Alpinetin chalcone., aretigenin, Arctiin, asiatic acid, asiaticoside, bergamottin, bergapton, betanin, dioscin, galangin, cimicifugoside, cinnamic acid, ferulic acid, fumaric acid, alpha-lipoic acid, carnosine, VBT, caffeic acid, ellagic acid, Crataegolic acid, CAPE, CAPE, theobromine, theophylline, caffeoylquinic acids, ursolic acid, garlicin, zingiberol, shogaol, piperine, bilobalide, ginkgetin, ginsenoside, Radix Astragali saponin, Cycloastragenol, danshensu, tanshinol, the new elder brother of Radix Salviae Miltiorrhizae, TANSHINONES, Radix Salviae Miltiorrhizae diketone, rosmarinic acid, diosmin, Nobiletin, Pericarpium Citri tangerinae element, luteolin, phylloxanthin, β-lycopene, cryptoxanthin, butyl alcohol, hypericin, hyperin, Quercetin, Quercitroside, isoquercitrin, hydroxytyrosol, Luo Sailin, rosasterol, network plug is tieed up, network fine linen, Punicalagin, 4,6-(S,S)-Gallagyl-D-glucose, ampelopsin, myricetrin, kaempferol, dihydromyricetin, apigenin, naringin, naringenin, honokiol, magnolol, chimonin, mangostin, hesperetin, Hesperidin, lupeol, indole-3-methanol, genistein, genistin, Daidzein, daidzin, cynarin, bilobalide, bilobetin Bilobetin, epimedin, sulforaphen, phloretin, phloretin-primaverose, phlorhizin, oligomeric proanthocyanidin, PB1, procyanidin B 2, PC1, silibinin, rutin, wogonin, morin, Morusin, Mulberroside A, mulberry skin glucoside B, glycyrrhizic acid, enoxolone, linarin, protodioscin, former Gracillin, Neosynephrine, Lay bud enlightening glycosides A, stevioside, vitexin, Saponaretin, vitexin-4, vitexin-4''-O-glucoside, apigenin-8-C-glucoside-2 "-O-rhamnoside, apigenin-8-C-glucoside-4'-rhamnoside, alpha-tocopherol, betatocopherol, Gamma-Tocopherol and Delta-Tocopherol,

(2) described natural extract comprises: Fructus Mali pumilae extract, green tea extract, black tea extract, Rhizoma Curcumae Longae extract, Pericarpium Citri tangerinae extract, Fructus Rubi extract, blueberry extract, mulberry extract, the selection Cranberry extract of Punica granatum L. extract, Radix Ginseng extract, Rhizoma Zingiberis Recens extract, Fructus Piperis extract, wolfberry fruit extract, Fructus Hippophae extract, Radix Puerariae extract, Flos Caryophylli extract, Fructus Cannabis extract, Semen Cassiae extract, Cortex Magnoliae Officinalis extract, Semen Myristicae extract, Fructus Jujubae extract, Flos Lonicerae extract, Poria extract, Fructus Vitis viniferae extract, Semen Vitis viniferae extract, Semen Ginkgo extrac, Bulbus Allii extract, Resina garciniae extract, Fructus Lycopersici esculenti extract, coffee bean extract, Fructus Canrii Albi extract, mango extract, Fructus Momordicae charantiae extract, Radix Platycodonis extract, Folium Nelumbinis extract, Folium perillae extract, seed of Sesamum indicum L. extract, Radix Angelicae Sinensis extract, Elettaria cardamomum (L.) Maton extract, Cortex Cinnamomi extract, Black Cohosh P.E, Herba Epimedii extract, Fructus Schisandrae Chinensis extrat, Radix Salviae Miltiorrhizae extract, Rhizoma Curcumae Longae extract, Radix Astragali extract, Aloe extract, Radix Rhodiolae extract, Citrus reticulata Blanco extract, Citrus reticulata Blanco extract, citron extract, Caulis et Folium Brassicae capitatae, Radix Glycyrrhizae extract, globe artichoke leaf extract, Herba Taraxaci extract, Fructus Crataegi extract, Semen Cuscutae extract, Semen Trigonellae extract, Herba Centellae extract, Herba portulacae extract, tribulus terrestris extraction, Stevia rebaudiana (Bertoni) Hemsl extract, Lu Han extract, Flos lupuli (Flos Humuli Lupuli) extract and Folium Menthae extract.

2. compositions according to claim 1, it is characterized in that, wherein enrichment or the natural crocin of purification be at least following in one: crocin-I, crocin-II, crocin-III, crocin-IV, α-crocetin-two (β-D-glucityl) ester, α-crocetin-mono--β-D-glucityl ester, 13-cis-α-crocetin-two (β-D-gentiobiose base) ester, 13-cis-α-crocetin β-D-gentiobiose-β-D-glucityl ester, and the natural analog be present in Stigma Croci or cape jasmine fruit or Gardenia Yellow.

3. compositions according to claim 1, it is characterized in that, described crocin and/or α-crocetin, purity is 50%-100%.

4. compositions according to claim 1, it is characterized in that, the content of crocin described in compositions and/or α-crocetin is greater than 1wt%.

5. compositions according to claim 1, it is characterized in that, described compositions comprises the following composition of percentage by weight: crocin or α-crocetin or both jointly account for 1-60%, green tea extract 1-50%, curcumin 1-40%, resveratrol 1-40%, Radix Ginseng extract 1-40%, alpha-lipoic acid 0.5-20%, and L-carnitine 0.1-20%; The percentage ratio sum of each component is 1.

6. compositions according to claim 1, it is characterized in that, described compositions comprises the following composition with percentage by weight, citric acid 10-60%, potassium bicarbonate 5-40%, sodium bicarbonate 5-40%, 0.5-20% sodium carbonate, crocin or α-crocetin or both common 0.5-30%, Polyethylene Glycol 0.2-10%, A Si BATANG 0.1-8%, flavoring agent 0.1-5%; The percentage ratio sum of each component is 1.

7. compositions according to claim 1, it is characterized in that, described compositions is fluffy lyophilized products, wherein crocin or α-crocetin or both jointly account for 10%-99%(weight), and wherein said compositions only need by add water or normal saline or 5% glucose solution or 5% glucose or cyclodextrin or its combination liquid in mixing, shake and do not need machined a little, can obtain injectable solution or suspension or emulsion.

8. compositions according to claim 1, it is characterized in that, compositions is made into dosage form or form below: tablet, soft gel, capsule, pill, lozenge, dragee, granule, powder, injection, can reassemble into the powder for injection of injection, or effervescent tablet, liquid, spray, functional food, chewing gum, chewing gum compositions, taffy, caramel confection, soft sweet, degradable films, the thin film of not degrading, hard sugar, liquid beverage, or beverage.

9. compositions according to claim 1, it is characterized in that, described compositions can be made into discharge immediately, mixing release, or the composition product of enteric coating form, or mixing release composition is double-layer coatings tablet.

10. the compositions according to claim 1-6 any one is in pharmacy, and health product, apply in functional food and cosmetics.