CN102905529B - Compositions comprising non-acidic boswellia oil fraction as bio-enhancer for enhancing the bioavailability of biological agents - Google Patents
Compositions comprising non-acidic boswellia oil fraction as bio-enhancer for enhancing the bioavailability of biological agents Download PDFInfo
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Abstract
The invention relates to Boswellia derived fraction selected from non-acidic Boswellia low polar gum resin extract fraction (BLPRE), Boswellia volatile oil fraction (BVOIL) or Boswellia oil fraction (BOIL) comprising BLPRE and BVOIL in combination with biological agents for enhancing the bioavailability of said biological agents. The invention also provides composition(s) comprising at least one component selected from Boswellia oil (BOIL), Boswellia volatile oil (BVOIL) and Boswellia low polar gum resin extract (BLPRE) in combination with a biological agent for increasing the bioavailability of biological agent.
Description
invention field:
The invention provides the low polarity gum resin of nonacid frankincense extract fraction (BLPRE), frankincense ethereal oil fraction (BVOIL) or contain BLPRE and the frankincense oil fraction of BVOIL (BOIL) for improving the bioavilability of biologic product.
Provided by the invention for improving the composition of the bioavilability of biologic product, it at least contains a kind of component of being selected from frankincense oil (BOIL), frankincense ethereal oil (BVOIL) and the low polarity gum resin of frankincense extract (BLPRE) and in conjunction with a kind of biologic product.
goal of the invention:
Many medicines, medicinal herb components and bioactive molecule are all very effective to disease or obstacle in vitro.Yet some of them in vivo (warm blooded animal) do not have effect or there is no bioavailability.Therefore the bioavilability that, research, identification and invention safety and effectively preparation help to improve drug ingedient is very important.In the present invention, inventor has screened a large amount of extract that comes from plant, animal and microorganism, fraction, plant chemical ingredient and compound.
background of invention:
Since ancient times gum olibanum fat tool have been widely used.For example, for example the gum resin of boswellia serrata tree plant is just used for the treatment of rheumatoid arthritis and gout by the herbal medicine people industry personage of India's medical system for a long time.The various extracts of gum resin on laboratory animal, all shown potential anti-inflammatory and antiatherosclerosis active [CuaZ-Perolin et al.,
arteriosclerThrombVascBiolFeb2008].It is found that, Olibanum extract is a kind of potential anti-arthritic [Kimmatkar et al;
phytomedicine. 2003,10 (1): 3-7].Gum olibanum fat and extract thereof are also proved and can significantly improve curative effect in human clinical test, shown anti-inflammatory effect in body [E Ernest, BMJ 2008; 337:a2813].
It is due to one group of triterpenic acid that gum olibanum fat and extract thereof have antiinflammation, and masticinic acid, is separated acquisition from the gum resin of boswellia serrata.Masticinic acid demonstrates antiinflammation by suppressing 5-lipoxygenase (5-LOX).The enzyme of a kind of key when 5-LOX is arachidonic acid synthesis leukotriene.Cyperus iria L. martimi is considered to the generation of inflammation disease and develops relevant.In addition masticinic acid suppresses 5-lipoxygenase, thereby suppresses human leukocytes elastoser (HLE), the enzyme in the proinflammatory disease of a kind of difference path Safayahi, H., et. al., J. and Pharmacol. Exp. Ther., 1997:281; P 460-463 ］.3-O-acetyl group-11-ketone-beta boswellic acid (AKBA) is the composition that biologic activity is the strongest in it is similar, and it suppresses the IC of 5-LOX
50be 1.5 μ M[Sailer, E.R., et. al., British J. Pharmacol., 1996:117; P 615-618].
US Patent No. 5716928 and US5665386 relate to a kind of method that increases the bioavilability of oral dewatering medicament compound, comprise when needing the mammal oral drugs compound of compounds for treating, follow essential oil or the essential oil component of q.s, make the bioavilability of compound when there is essential oil or essential oil component be greater than the bioavilability of compound while there is no essential oil or essential oil component, wherein essential oil or essential oil component are at 0.01wt or still less to have 10% inhibition during concentration active, the minimizing that changes hydroxylation product by measuring cyclosporine into is analyzed, utilization contains 250mug rat liver microsome in the sodium phosphate buffer of the 0.1MPH7.4 of 1 milliliter, the analytical system of 1mu cyclosporine and 1mM NADPH (NADPH).
Required the PCT application WO02/15916 of the priority of German patent DE-A10041217 to disclose the dihydro masticinic acid that is derived from frankincense, the acceptable salt of its medicine and hydrogenation extract.Described disclosed patent suggestion prevents and/or treats unwelcome psychosomatic with these compounds, especially health, body and mind and mental illness, the inflammatory process causing as the rising of the increase by leukotriene formation volume, leukocyte elastase or plasmin activity.
According to inventor's understanding, in prior art, do not relate to by the low polarity gum resin of nonacid frankincense fraction (BLPRE), frankincense ethereal oil fraction (BVOIL) or contain BLPRE and the frankincense oil fraction of BVOIL (BOIL) for increase the bioavilability of biologic product warm blooded animal.
Nearly 30% old American does not obtain the dietary requirements of all essential nutriments.When using up essential nutriment, the harm of food-drug interaction is well-known.The use that the elderly need to increase medicine is inevitable.For example, use specific antibiotic can reduce the absorption of calcium and iron, and EDTA chelation therapy can reduce the absorption of zinc, iron, copper and magnesium.
In addition, the much food of the risk increase of cancer and angiocardiopathy that makes must be removed from diet, thereby further consumes the source of essential nutriment.For example, the good source of Cobastab and vitamin D, as red meat, liver, yolk, cheese and dairy produce, restricted often, because their cholesterol level is high.
Limited menu also causes the consumption of essential amino acid, and as tryptophan, this is the precursor of very important neurotransmitter, and may the effect with performance aspect the degeneration at age at prevention brain.Availability that must nutriment is because gastrointestinal absorption is poor and further suffer damage.
The traditional approach that makes up the metabolism underutilization of nutritional supplementation deficiency, gastrointestinal absorption deficiency and nutriment is the compensation material of n of high dose oral, as vitamin and mineral supplements.
Therefore, be starved of the compound/composition that exploitation contributes to improve the availability of biologic product, by comprising, improve bioavilability, improve serum-concentration, improve gastrointestinal absorption, the utilization of improvement system, improve some biological barrier for example the intersection between the skin of respiratory mucosa, mucous membrane of urethra, blood-brain barrier and warm blooded animal be communicated with in one or more interior mechanism.
summary of the invention:
An importance of the present invention is to provide frankincense oil (BOIL) for improving the bioavilability of biologic product.
Another importance of the present invention is to provide frankincense ethereal oil fraction (BVOIL) for improving the bioavilability of biologic product.
Another importance of the present invention is to provide the low polarity gum resin of frankincense and extracts fraction (BLPRE) for improving the bioavilability of biologic product.
Another aspect of the present invention is to provide the composition that improves the bioavilability of biologic product in the warm blooded animal of needs, and it at least contains a kind of component in the low polarity gum resin of the frankincense extract (BLPRE) that is selected from frankincense oil (BOIL), frankincense ethereal oil (BVOIL) and comes from gum olibanum fat in conjunction with a kind of biologic product.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense for improving the bioavilability of one or more biotic components or functional components.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense for improving the bioavilability of one or more medicine goods/synthetic drugs.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense for improving the bioavilability of one or more frankincense compositions derived therefroms.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense for improving the bioavilability of one or more turmeric compositions derived therefroms.
accompanying drawing explanation:
Figure I: the structural formula 1-9 showing in figure represents that boswellia serrata sets the representative compound of low polarity gum resin extract (BSLPRE).
Figure II is the serum-concentration diagram of the AKBA that shows, the dosage to be equivalent to 30mg/kgAKBA to albino rat oral contain boswellia serrata set low polarity gum resin extract (BSLPRE) and selectivity be concentrated into 30%3-O-acetyl group-11-ketone group-masticinic acid (AKBA) boswellia serrata tree extract composition LI13108F and contain boswellia serrata tree ethereal oil fraction (BsVOIL) and boswellia serrata that selectivity is concentrated into 30%3-O-acetyl group-11-ketone group-masticinic acid (AKBA) is set after the composition LI13119F of extract.
Figure III is the serum-concentration diagram of the dinor-curcumin (LI01008) that shows, with concentration 450mg/kg oral contain dinor-curcumin and boswellia serrata to set the composition (LI13124F1) that low polarity gum resin extract (BSLPRE) mixes with the ratio of 2:1 after or after the independent oral dinor-curcumin of concentration (LI01008) with 300mg/kg body weight.
detailed Description Of The Invention:
1, " frankincense oil " used herein or " nonacid Olibanum extract " or " BOIL " representative contains the nonacid gum olibanum fat extract that the low polarity gum resin of the nonacid frankincense obtaining from the gum resin of any Boswellia extracts fraction (BLPRE) and frankincense ethereal oil fraction (BVOIL).
2, the nonacid boswellia serrata that contains that the gum resin that " boswellia serrata tree oil " used herein or " nonacid boswellia serrata tree extract " or " BsOIL " representative are set from boswellia serrata obtains is set the nonacid boswellia serrata tree gum resin extract that low polarity gum resin extracts fraction (BsLPRE) and boswellia serrata tree ethereal oil fraction (BsVOIL).
3, " Ka Shi Boswellia carterii oil " used herein or " nonacid Ka Shi Boswellia carterii extract " or " BcOIL " representative contain the nonacid Ka Shi gum olibanum fat extract that the low polarity gum resin of the nonacid Ka Shi Boswellia carterii obtaining from the gum resin of any Ka Shi frankincense seeds extracts fraction (BcLPRE) and Ka Shi Boswellia carterii ethereal oil fraction (BcVOIL).
4, " the low polarity gum resin of frankincense extracts fraction " used herein or " the low polarity gum resin of frankincense extract " or " BLPRE " represent nonacid gum olibanum fat extract oil fraction, it contains and from frankincense oil, has removed sesquiterpene, diterpene, triterpenes and other the oiliness phytochemicals obtaining after volatile component, and described frankincense oil is by described any method, to obtain from the gum resin of any Boswellia.
5, " the oily low polarity gum resin of boswellia serrata tree extracts fraction " used herein or " boswellia serrata is set low polarity gum resin extract " or " BsLPRE " represent nonacid boswellia serrata tree gum resin extract oil fraction, it contains and from frankincense oil, has removed sesquiterpene, diterpene, triterpenes and other the oiliness phytochemicals obtaining after volatile component, and described frankincense oil is by described any method, to obtain from the gum resin of boswellia serrata tree.
6, " the low polarity gum resin of Ka Shi Boswellia carterii extracts fraction " used herein or " the low polarity gum resin of Ka Shi Boswellia carterii extract " or " BcLPRE " represent nonacid Ka Shi Boswellia carterii gum resin extract oil fraction, it contains and from Ka Shi Boswellia carterii oil, has removed sesquiterpene, diterpene, triterpenes and other the oiliness phytochemicals obtaining after volatile component, and described Ka Shi Boswellia carterii oil is by described any method, to obtain from the gum resin of Ka Shi frankincense seeds.
7, " frankincense ethereal oil fraction " used herein or " frankincense ethereal oil " or " ethereal oil " or " volatility fraction " or " BVOIL " represent volatility fraction/extract, and it contains the gum resin from any Boswellia obtains by described arbitrarily method monoene, diterpene, ethereal oil and other oiliness phytochemicals.
8, " boswellia serrata tree ethereal oil fraction " used herein or " boswellia serrata tree ethereal oil " or " tingia ethereal oil " or " tingia volatility fraction or " BsVOIL " represent volatility fraction/extract, and it contains monoene, diterpene, ethereal oil and other the oiliness phytochemicals obtaining from the gum resin of boswellia serrata tree by described arbitrarily method.
9, " Ka Shi Boswellia carterii ethereal oil fraction " used herein or " Ka Shi Boswellia carterii ethereal oil " or " Ka Shi ethereal oil " or " Ka Shi volatility fraction or " BcVOIL " represent volatility fraction/extract, and it contains monoene, diterpene, ethereal oil and other the oiliness phytochemicals obtaining from the gum resin of any Ka Shi Boswellia carterii by arbitrarily described method.
10, " natural gum " used herein or " gum resin " or " resin " represent the secretion of frankincense plant species.
11, " plant chemical ingredient " used herein representative separated pure or half pure compound from plant.
12, " bio-enhancer " refers in warm blooded animal the reagent that improves biologic product availabilities by one or more mechanism, mechanism wherein comprise improve bioavilability, improve serum-concentration, improve gastrointestinal absorption, the utilization of improvement system, improve some biological barrier for example the intersection between respiratory mucosa, mucous membrane of urethra, blood-brain barrier and skin be communicated with.
13, " Bioenhanced compositions " refers to and contains the composition in conjunction with one or more biologic products as the frankincense derived oils fraction of bio-enhancer.
14, " biologic product " refers to one or more preparations that are selected from from bioactive ingredients, functional components, antioxidant, vitamin, mineral matter, amino acid and oil of plant/animal/microorganism/synthetic or semi-synthetic acquisition and composition thereof.
15, " BSE85 % " used herein refers to the boswellia serrata extract that is standardized as 85% masticinic acid.
16, " BCE85% " used herein refers to the Ka Shi Olibanum extract that is standardized as 85% masticinic acid.
17, " CLE95 % " refers to the Turmeric P.E that is standardized as 95% curcumin.
18, " CAE20 % " refers to the Radix Curcumae extract that is standardized as 20% curcumin.
19, " bioactive ingredients " refers to acceptable active component in pharmaceutically any or alimentology or on diet; Come from compound, extract, fraction, phytochemicals, synthetic drug plant, animal or microorganism or that by chemosynthesis or semisynthesis, obtain, or their salt or their mixture.
20, " functional components " refers to and comes from plant or animal or microorganism or chemosynthesis or semisynthetic any medicinal herb components, dietary supplements, antioxidant, vitamin, mineral matter, amino acid, fatty acid, essential oil, fish oil, enzyme, gucosamine, chondroitin and probio or their salt or their mixture.
The gum resin of frankincense has just obtained application very widely since ancient times.The various Boswellias for example gum resin of boswellia serrata tree, Ka Shi Boswellia carterii or frankincense Chinese holly tree are the complex mixtures that contains frankincense oil fraction (BOIL), masticinic acid, carbohydrate and polysaccharide component, and wherein frankincense oil fraction (BOIL) contains essential oil/Olibanum volatile oil fraction (BVOIL) and the low polarity gum resin extraction of nonacid frankincense fraction (BLPRE).Widely used boswellia serrata tree/Ka Shi Boswellia carterii/frankincense Chinese holly tree extract is from the isolated acid fraction of gum resin in the international market, and this fraction is by the standardized 65% or 85% total masticinic acid that contains by analysis by titration.To coming from the conventional Olibanum extract (85% total masticinic acid) of boswellia serrata tree/Ka Shi Boswellia carterii/frankincense Chinese holly tree, carrying out in commercialization process, the sour fraction that mainly comprises the triterpenic acid that contains masticinic acid is separated acquisition of remainder from gum resin.In total masticinic acid concentration process, sugar and other polymer are separated and are entered water.The insoluble low polar compound of remaining water is separated and becomes frankincense oil fraction/extract.The compound of these low polarity does not exist or with the low Olibanum extract that is standardized as the business Olibanum extract of masticinic acid and optionally concentrates in 3-O-acetyl group-11-ketone group-beta boswellic acid (AKBA) of being present in of extremely low concentration in the two.
obtain the method for nonacid frankincense oil (BOIL) fraction:
A typical method that obtains frankincense oil comprises:
A) obtain the gum resin of one or more plants, described plant be selected from but be not limited to boswellia serrata tree or Ka Shi Boswellia carterii or/frankincense Chinese holly tree or their mixture,
B) utilize water-insoluble organic solvents extraction gum resin,
C) carefully filter extract to remove insoluble resin material.
D) utilize aqueous alkali as potassium hydroxide aqueous solution cyclic washing extractive with organic solvent,
E) utilize water and salt water washing organic layer, and
F) under vacuum and high temperature, evaporate organic layer, to obtain oily residue (BOIL).
obtain the method for frankincense ethereal oil (BVOIL) fraction:
The method that obtains frankincense ethereal oil (BVOIL) is by steaming or utilize high vacuum from gum olibanum fat.
(BVOIL) typical method that obtains frankincense ethereal oil comprises:
A) obtain the gum resin of frankincense, and
B) from described gum resin or by steaming or under high vacuum, low temperature, distill and isolate ethereal oil component, to obtain BVOIL.
In another replaceable method,
A) BOIL is prepared by said method,
B) then by BOIL steaming or vacuum distillation to collect frankincense ethereal oil (BVOIL).
obtain the method for frankincense low polarity gum resin extract (BLPRE) fraction:
A typical method that obtains frankincense low polarity gum resin extract (BLPRE) comprises:
A) utilize the gum resin of water-insoluble organic solvents extraction frankincense Pterostyrax, then carefully filter extract to remove insoluble resin material,
B) utilize aqueous alkali as potassium hydroxide aqueous solution cyclic washing extractive with organic solvent,
C) organic layer obtaining after detergent water and salt solution alkali cleaning,
D) under vacuum and high temperature, evaporate described organic layer to obtain oily residue, and
E) under high vacuum and high temperature, from described oily residue, remove volatile compound to obtain BLPRE.
Another typical method that obtains frankincense low polarity gum resin extract (BLPRE) comprises:
A) prepare alcohols or the hydration alcohols extract of gum olibanum fat,
B) between aqueous alkali and water-insoluble organic solvents, isolate alcohols extract,
C) Separation of Organic layer, then evaporating solvent to be to obtain oily residue, and
D) under high temperature and high vacuum, from described oily residue, remove volatile compound to obtain BLPRE.
Also have another typical method that obtains frankincense low polarity gum resin extract (BLPRE) to comprise:
A) utilize the gum resin of alcohols or hydration alcohols extracting Boswellia,
B) evaporation organic solvent is to the optimum level of total solid matters, then
C) it be alkaline adjusting pH value, PH9-12 preferably,
D) utilize organic solvent to repeat to extract solution,
E) under vacuum and high temperature, evaporate organic solvent to obtain oily residue, and
F) under high vacuum and high temperature from described oily residue evaporating volatile compound to obtain BLPRE.
A typical method that obtains boswellia serrata tree ethereal oil (BsVOIL) comprises:
A) obtain the gum resin of boswellia serrata tree, and
B) from described gum resin or by steaming or under high vacuum, low temperature, distill and isolate ethereal oil component, to obtain BsVOIL.
Another typical method that obtains Ka Shi Boswellia carterii ethereal oil (BcVOIL) comprises:
A) obtain the gum resin of Ka Shi Boswellia carterii, and
B) from described gum resin or by steaming or under high vacuum, low temperature, distill and isolate ethereal oil component, to obtain BcVOIL.
The typical method that obtains frankincense ethereal oil (BVOIL) from boswellia serrata tree, Ka Shi Boswellia carterii as mentioned above.Yet, can from frankincense Pterostyrax, obtain any gum resin for making frankincense ethereal oil (BVOIL) by similar method or process.
Obtain boswellia serrata and set the typical method of low polarity gum resin extract (BsLPRE):
A) obtain the gum resin of boswellia serrata tree,
B) utilize water-insoluble organic solvents extraction, then by filtering to isolate insoluble gummy material and abandoning,
C) utilize the aqueous alkali cyclic washing extractive with organic solvent of dilution to remove acid compound,
D) water and salt water washing organic layer in succession,
E) under vacuum and 60-70 ° of C, evaporate organic layer to obtain oily residue, and
F) under high vacuum and high temperature, from described oily residue, remove volatile component to obtain viscous oil, the boswellia serrata being is herein set low polarity gum resin extract (BsLPRE).
Alternatively, BsLPRE also can be prepared by the following method:
A) prepare alcohols or the hydration alcohols extract of boswellia serrata tree gum resin,
B) between aqueous alkali and water-insoluble organic solvents, isolate alcohols extract,
C) Separation of Organic layer then evaporates organic layer to obtain oily residue under vacuum and 60-70 ° of C, and
D) under high vacuum and high temperature, from described oily residue, remove volatile component to obtain viscous oil, the boswellia serrata being is herein set low polarity gum resin extract (BsLPRE).
Another typical method that obtains Ka Shi Boswellia carterii low polarity gum resin extract (BcLPRE) comprises:
A) obtain the gum resin of Ka Shi Boswellia carterii,
B) utilize water-insoluble organic solvents extraction gum resin, then by filtering to isolate insoluble gummy material and abandoning,
C) utilize the aqueous alkali cyclic washing extractive with organic solvent of dilution to remove acid compound,
D) water and salt water washing organic layer in succession,
E) under vacuum and 60-70 ° of C, evaporate organic layer to obtain oily residue, and
F) under high vacuum and high temperature, from described oily residue, remove volatile component to obtain viscous oil, be the low polarity gum resin of Ka Shi Boswellia carterii extract (BcLPRE) herein.
Alternatively, BcLPRE also can be prepared by the following method:
A) prepare alcohols or the hydration alcohols extract of Ka Shi Boswellia carterii gum resin,
B) between aqueous alkali and water-insoluble organic solvents, isolate alcohols extract,
C) Separation of Organic layer then evaporates organic layer to obtain oily residue under vacuum and 60-70 ° of C,
D) under high vacuum and high temperature, from described oily residue, remove volatile component to obtain viscous oil, be the low polarity gum resin of Ka Shi Boswellia carterii extract (BcLPRE) herein.
From boswellia serrata tree and Ka Shi Boswellia carterii, obtain the typical method of the low polarity gum resin of frankincense extract (BLPRE) as mentioned above.Yet, can from frankincense Pterostyrax, obtain any gum resin for making low polarity gum resin extract by similar method or process.
Described former frankincense oil (BOIL) or Olibanum volatile oil (BVOIL) or the low polarity gum resin of frankincense extract (BLPRE) have formed the main component of gum olibanum fat.Yet it has limited commercial use, and it usually abandons as waste material.The potential use of these fractions is slowly undiscovered.Inventor is surprised to find that from boswellia serrata tree oil, removing the fraction obtaining after volatile compound is that boswellia serrata is set low polarity gum resin extract (BsLPRE) and had some useful character.
In the Indian patent application 2229/CHE/2008 submitting on September 15th, 2008 before us and the PCT application PCT/IN2009/000505 submitting on September 14th, 2009, we disclose and have comprised the Synergistic compositions that the concentrated fraction of AKBA and boswellia serrata are set nonacid extract (BNRE).BNRE composition and recognition methods thereof are also open in the lump.
At us, be bordering on most in the Indian patent application 394/CHE/2010 submitting on February 15th, 2010, we disclose non-masticinic acid fraction and Synergistic compositions thereof.
In the process of research bio-enhancer, inventor surprisingly finds, the low polarity gum resin of nonacid frankincense extracts fraction (BLPRE), frankincense ethereal oil fraction (BVOIL) or contains BLPRE and the frankincense oil fraction of BVOIL (BOIL) can improve the bioavilability of bioactivator.To contain boswellia serrata and set low polarity gum resin extract (BSLPRE; LI13115) and selectivity be concentrated into 30%3-O-acetyl group-11-ketone group-beta boswellic acid (AKBA) boswellia serrata tree extract composition LI13108F and contain boswellia serrata tree ethereal oil fraction (BsVOIL) and composition LI13119F that boswellia serrata that selectivity is concentrated into 30%3-O-acetyl group-11-ketone group-beta boswellic acid (AKBA) is set extract gives to albino rat.The animal of control group gives the boswellia serrata tree extract that selectivity is concentrated into 30%AKBA.Before oral test substances and respectively during 0.5,1,2,4,8 hour after oral, collect the blood sample of all animals.Utilize LC-MS by measuring the serum AK BA concentration of each test animal, to analyze the oral administration biaavailability of the AKBA in comparison frankincense material.
Surprisingly, composition LI13108F and composition LI13119F have shown good oral administration biaavailability, be respectively AUCs14.08 and 11.23, and the AUC of the component (LI13115) of only having boswellia serrata tree extract that comprises 30%AKBA is 9.825.The bioavilability of LI13108F (with AUC opinion) is higher by 43.33% than LI13115.The bioavilability of LI13119F is higher by 14.33% than LI13115.The details of research is as described in embodiment 6 and figure II.
In order to reach best result for the treatment of, active substance should and arrive its avtive spot with the circulation of valid density perfect aspect during required.Improve bioavilability and reduce medicine frequency and do not lose result for the treatment of for realizing result for the treatment of and being vital for the compliance of patient in chronic treatment.The present invention realizes this object by improving the oral administration biaavailability of AKBA in the composition that contains BsLPRE or BsVOIL.
The composition (LI13124F1) that contains BSLPRE and new dinor-curcumin by name (LI01008) by comparative analysis in albefaction rat and independent LI01008 further confirm to improve the effect of the bioavilability of BsLPRE.Dinor-curcumin is a kind of potent curcumin chemical compounds, is much better than the non-oxidizability of other other natural curcumin chemical compounds and the other biological of the curcumin of performance is active conventionally.Compare with the animal of independent supply LI01008, in serum sample, the bioavilability of composition LI13124F1 is better than LI01008.Compare with the independent serum sample of supplying with the animal of LI01008, the serum sample of supplying with the animal of composition LI13124F1 demonstrates the bioavilability that exceeds 75%.Experimental study is described in embodiment 6 and figure III.
The low polarity gum resin of the nonacid frankincense of above description of contents extract (BLPRE), frankincense ethereal oil fraction (BVOIL) or contain BLPRE and the frankincense oil fraction of BVOL (BOIL) improves the bioavilability of bioactivator.Therefore the dosage that, these bio-enhancers can be used for improving curative effect and reduce bioactivator.
various embodiments of the invention will be described below:
An importance of the present invention is to provide for improving the bio-enhancer of the bioavilability of biologic product, is selected from frankincense oil (BOIL), frankincense ethereal oil (BVOIL) originally and comes from the low polarity gum resin of the frankincense extract (BLPRE) of the gum olibanum fat of frankincense seeds.
An importance of the present invention is to provide for improving the composition of the bioavilability of biologic product, and the frankincense oil that contains one or more scripts that are selected from (BOIL), frankincense ethereal oil (BVOIL) and the composition of the low polarity gum resin of frankincense extract (BLPRE) of gum olibanum fat that comes from frankincense seeds are in conjunction with a biologic product.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense, for improving bioavilability and/or biological effectiveness or the dietary supplements relevant with animal also except important to the mankind.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense, for improving the bioavilability of one or more biotic components or functional components.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense, for improving the bioavilability of one or more frankincense compositions derived therefroms.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense, for improving the bioavilability of one or more turmeric compositions derived therefroms.
Another aspect of the present invention is to provide the method for utilizing the derivative bio-enhancer of frankincense to improve the bioavilability of biologic product.
Another aspect of the present invention is to provide the bio-enhancer playing a role by one or more mechanism, mechanism wherein comprise improve bioavilability, improve serum-concentration, improve gastrointestinal absorption, the utilization of improvement system and improve some biological barrier for example the intersection between respiratory mucosa, mucous membrane of urethra, blood-brain barrier and skin be communicated with.
Another aspect of the present invention is to provide frankincense oil (BOIL), frankincense ethereal oil (BVOIL) and comes from the bio-enhancer of the low polarity gum resin of the frankincense extract (BLPRE) of Boswellia gum resin, and wherein this gum resin can acquisition from be selected from frankincense kind one or more of boswellia serrata tree, Ka Shi Boswellia carterii and frankincense Chinese holly tree.
Another aspect of the present invention is to provide for the biological active composition that improves biologic product of the warm blooded animal at needs.
Another aspect of the present invention is to provide for improve the composition of the bioavilability of nutrition or diet composition the warm blooded animal of needs, and it contains frankincense oil (BOIL), frankincense ethereal oil (BVOIL) and the low polarity gum resin of frankincense extract (BLPRE).
On nutrition/diet, acceptable reagent comprises one or more compositions, this composition is selected from phytochemicals, short intelligence agent, antiobesity agent, antiinflammatory, antilipemic agent, Antiarthritic agent, antidiabetic, antimicrobial, antifungal agent, antitumor agent, drug for hypertension, anodyne, anti-platelet aggregation agent, antiatherosclerotic, antioxidant, antithrombotic agent, antibacterial agent, anti-antimalarial agent, anti-osteoporosis agent, probiotics, antifungal agent, immunopotentiator, antivirotic, antihistaminic, muscle relaxant, CI, hypnotic and their salt.
Another aspect of the present invention is to provide for improving the composition of one or more biotic components, and this biotic component is selected from synthetic/semisynthetic bioactive ingredients, functional components, medicinal herb components, dietary supplements, nutriment, antioxidant, vitamin, mineral matter, amino acid and oil and their mixture from plant/animal/microorganism.
Described functional components comprises and is selected from nutriment, dietary supplements, nutrient component, medicinal herb components, phytochemicals, animal protein, gucosamine, chondroitin, phytoprotein, fruit extract, animal extracts, algae extract, probio and their salt.
Described medicinal herb components comprises one or more compositions, and this composition is selected from and is derived from Withania kansuensis, bacopa monnieri, frankincense kind, turmeric kind, centella, Herba Sphaeranthi indici, sugar-apple, the full wing elm of entire leaf, betel, horse gram, Moringa and the extract/fraction/phytochemicals of kamuning and their salt.
Described antioxidant comprises one or more compositions, is selected from vitamin A, vitamin C, vitamin E, alpha-carotene, anti-beta carotene, β kryptoxanthin, lycopene, xanthophyll/zeaxanthin, the yellow alkali alcohol of pine bark biological species compound, germanium, selenium and zinc.
Described vitamin comprises one or more water soluble vitamins, is selected from Cobastab l, vitamin B2, vitamin PP, vitamin B6, Cobastab l2, folic acid and vitamin C; Lipovitamin, is selected from vitamin A, vitamin D, vitamin E and vitamin K.
Described mineral matter comprises one or more mineral matters that is selected from calcium, iron, zinc, vanadium, selenium, chromium, iodine, potassium, manganese, copper and magnesium.
Described amino acid comprises one or more amino acid that is selected from lysine, isoleucine, leucine, threonine, valine, tryptophan, phenyl alanine, methionine, L-selenomethionine and composition thereof.
Described oil comprises one or more oil that is selected from omega-fatty acid, linseed oil, fish oil, krill oil, essential oil and volatile oil.
The biologically active of described frankincense derivative compound/phytochemical can improve by bio-enhancer; comprise that fractionation extract is standardized as one or more masticinic acids, be selected from α-masticinic acid, beta boswellic acid, 3-O-acetyl group-α masticinic acid, 3-O-acetyl group-β masticinic acid, 3-O-acetyl group-11-ketone group-α-masticinic acid, 11-ketone group-beta boswellic acid and 3-O-acetyl group-11-ketone group-beta boswellic acid.
Another aspect of the present invention is to provide bio-enhancer, be selected from frankincense oil (BOIL), frankincense ethereal oil (BVOIL) and from the low polarity gum resin of the frankincense extract (BLPRE) of frankincense gum resin for improving the particularly bioavilability of standardized 3-O-acetyl group-11-ketone group-beta boswellic acid (AKBA) of extract/fraction.
Another aspect of the present invention is to provide the derivative preparation of frankincense and composition; for improving the bioavilability of the phytochemicals that is derived from frankincense species; include but not limited to masticinic acid, be selected from α-masticinic acid, beta boswellic acid, 3-acetyl group-α masticinic acid, 3-acetyl group-β masticinic acid, 3-acetyl group-11-ketone group-α-masticinic acid and 3-O-acetyl group-11-ketone group-beta boswellic acid or their mixture.
For the preparation of described oil (BOIL) or ethereal oil (BVOIL) or the frankincense seeds that come from the low polarity gum resin extract (BLPRE) of gum resin, comprise one or more seeds, be selected from boswellia serrata tree (
boswellia serrata), Ka Shi Boswellia carterii (
boswellia carterii), frankincense Chinese holly tree (
boswellia papyrifera), Amire Boswellia carterii (
boswellia ameero), Bradley tower Boswellia carterii (
boswellia bullata), Da Reli Boswellia carterii (
boswellia dalzielii), this section Reed Boswellia carterii of Christian Dior (
boswellia dioscorides), wheat straw Boswellia carterii (
boswellia elongata), the Pood of section Boswellia carterii (
boswellia frereana), draw Boswellia carterii (
boswellia nana), wild Boswellia carterii (
boswellia neglecta), Ou Jiadengsi Boswellia carterii (
boswellia ogadensis), Pi Luota Boswellia carterii (
boswellia pirottae), amber amber Wella Boswellia carterii (
boswellia popoviana), Suo Biya Boswellia carterii (
boswellia rivae), sacred Boswellia carterii (
boswellia sacra) and Socotra Boswellia carterii (
boswellia socotrana).
Another aspect of the present invention is to provide frankincense oil or frankincense ethereal oil or the low polarity gum resin of frankincense extract for improving the bioavilability of the derivative extract/fraction/component/phytochemicals of one or more turmerics, by bio-enhancer, improve, comprise the standardized curcumin of fractionation extract, Demethoxycurcumin, Bisdemethoxycurcumin, demethyl curcumin, dinor-curcumin, tetrahydro curcumin, tetrahydrochysene Demethoxycurcumin, tetrahydrochysene Bisdemethoxycurcumin, ar-turmerone or their mixture.
Another aspect of the present invention is to provide bio-enhancer, be selected from frankincense oil (BOIL), frankincense ethereal oil (BVOIL) and from the low polarity gum resin of the frankincense extract (BLPRE) of frankincense gum resin for improving the particularly bioavilability of standardized curcumin or Demethoxycurcumin or Bisdemethoxycurcumin or their mixture of extract/fraction.
Another aspect of the present invention is to provide the derivative bio-enhancer of frankincense and for improving the bioavilability derived from one or more phytochemicalss of turmeric, is selected from curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, demethyl curcumin, dinor-curcumin, tetrahydro curcumin, tetrahydrochysene Demethoxycurcumin, tetrahydrochysene Bisdemethoxycurcumin, ar-turmerone or their mixture.
Can by the derivative component of the curcumin of Bioaugnentation derived from turmeric (
curcuma longa), root tuber of aromatic turmeric (
curcuma aromatica), family root tuber of aromatic turmeric (
curcuma domestica), curcuma zedoary (
curcuma aeruginosa), RADIX CURCUMAE from Sichuan of China (
curcuma albicoma), Ah Bi volt Lou like turmeric (
curcuma albiflora), Jiang Hehua (
curcuma alismatifolia), RADIX CURCUMAE (
curcuma angustifolia), large curcuma zedoary (
curcuma elata), rust curcuma zedoary (
curcuma ferruginea), chrysanthemum turmeric (
curcuma flaviflora), poppyhead curcuma zedoary (
curcuma yunnanensis) and curcuma zedoary (
curcuma zedoaria).
Another aspect of the present invention is to provide the typical method that obtains frankincense oil (BOIL), comprising:
A) obtain the gum resin of one or more plants, described plant be selected from but be not limited to boswellia serrata tree or Ka Shi Boswellia carterii or/frankincense Chinese holly tree or their mixture,
B) utilize water-insoluble organic solvents extraction gum resin,
C) carefully filter extract to remove insoluble resin material,
D) utilize aqueous alkali as potassium hydroxide aqueous solution cyclic washing extractive with organic solvent,
E) utilize water and salt water washing organic layer,
F) under vacuum and high temperature, evaporate organic layer to obtain oily residue (BOIL).
Another aspect of the present invention is to provide the typical method that obtains frankincense ethereal oil (BVOIL), comprising:
A) obtain the gum resin of frankincense,
B) from described gum resin or by steaming or at high vacuum and temperature, distill and isolate ethereal oil component, to obtain frankincense ethereal oil fraction (BVOIL).
C) alternatively, BVOIL fraction is separated from BOIL fraction by the mode of above-mentioned vacuum distillation at high vacuum and temperature.
Another aspect of the present invention is to provide the typical method of preparing the low polarity gum resin of frankincense extract (BVOIL), comprising:
A) utilize the gum resin of water-insoluble organic solvents extraction frankincense seeds, and carefully filter extract to remove insoluble resin material,
B) utilize aqueous alkali as potassium hydroxide aqueous solution cyclic washing extractive with organic solvent,
C) utilize the organic layer obtaining after water and salt solution washing alkali cleaning,
D) under vacuum and high temperature, evaporate described organic layer to obtain oily residue,
E) from described oily residue, remove volatile compound to obtain the low polarity gum resin of frankincense extract (BLPRE).
For the water-insoluble organic solvents extracting, be selected from without limitation 1,2-dichloroethane, n-hexane, carrene, chloroform, ethyl acetate, n-butanol, methyl iso-butyl ketone (MIBK) (MIBK) or their appropriate combination.For washing the aqueous alkali of extractive with organic solvent, be selected from group I or II group metal hydroxides, comprise without limitation sodium hydroxide, potassium hydroxide, slaked lime and magnesium hydroxide or their mixture.
On the other hand, a kind of selective method of preparing BLPRE comprises:
A) prepare alcohols or the hydration alcohols extract of gum olibanum fat,
B) between aqueous alkali and water-insoluble organic solvents, isolate alcohols extract,
C) Separation of Organic layer, then distills organic layer, obtains a kind of oiliness residue,
D) then under high vacuum and high temperature, the volatile compound in described oiliness residue is removed, obtained BLPRE.
On the other hand, also have a kind of selective method of preparing the low polarity gum resin of frankincense extract (BLPRE), comprising:
A) with alcohols or hydration alcohols, extract gum olibanum fat;
B) distillation organic solvent is to the optimum level of total solid, then
C) pH value is adjusted to alkalescence, is preferably pH9-12,
D) utilize organic solvent to repeat to extract solution,
E) under vacuum and high temperature, evaporate organic solvent, obtain oily residue,
F) under high vacuum and high temperature from described oily residue evaporating volatile compound, obtain BLPRE.
The alcohols using in extraction is selected from methyl alcohol, ethanol and propyl alcohol or their appropriate combination without limitation.
On the other hand, the invention provides the low polarity gum resin of the frankincense extract (BLPRE) that comes from boswellia serrata tree, wherein said extract comprises one or more Phytochemistry labeled compounds, be selected from without limitation guiol (guiol) (1), nephthenol (nephthenol) (2), serratol (serratol) (3), diterpene X (diterpene X) (4), lupeol (lupeol) (5), olive-12-alkene-3 β-ol (olean-12-ene-3 beta-ol) (6), olive-12-alkene-3 α-ol (olean-12-ene-3 α-ol) (7), wool steroid-8, 24-diene-3 α-ol (lanosta-8, 24-diene-3 α-ol) (8) and Usu-12-alkene-3 α-ol (urs-12-ene-3 α-ol) (9).
On the other hand, the invention provides and optionally remove the low polarity gum resin of the frankincense extract obtaining after acid and volatile compound.
The composition of the present invention that contains bio-enhancer and biologic product by oral, in skin, intravenous, subcutaneous, peritonaeum, in rectally, muscle or any suitable mode give warm blooded animal.
In warm blooded animal, effective every daily dose of bio-enhancer is the scope in 0.001-1500 mg/kg body weight.In warm blooded animal, effective every daily dose of bio-enhancer is the scope in 0.01-500 mg/kg body weight.
In warm blooded animal, effective every daily dose of bio-enhancer is the scope in 0.1-150 mg/kg body weight.
In warm blooded animal, effective every daily dose of bio-enhancer is the scope in 1.5-15 mg/kg body weight.
Embodiment:
Embodiment 1:
the method of preparing frankincense oil (BOIL) comprises:
The method of preparing frankincense oil comprises:
A) obtain the gum resin of one or more plants, described plant is selected from but is not limited to boswellia serrata tree or Ka Shi Boswellia carterii or frankincense Chinese holly tree or their mixture,
B) utilize water-insoluble organic solvents extraction gum resin,
C) carefully filter extract to remove insoluble resin material,
D) utilize aqueous alkali as potassium hydroxide aqueous solution cyclic washing extractive with organic solvent,
E) utilize water and salt water washing organic layer, and
F) under vacuum and high temperature, evaporate organic layer, obtain oily residue (BOIL).
Embodiment 2:
The method of preparing frankincense ethereal oil (BVOIL):
The method of preparing frankincense ethereal oil comprises:
A) obtain the gum resin of one or more plants, described plant is selected from but is not limited to boswellia serrata tree or Ka Shi Boswellia carterii or frankincense Chinese holly tree or their mixture,
B) from described gum resin or by steaming or under high vacuum, low temperature, distill and isolate ethereal oil component, obtain frankincense ethereal oil (BVOIL).
Embodiment 3:
boswellia serrata is set the preparation of low polarity gum resin extract (BsLPRE):
Boswellia serrata is set in methyl iso-butyl ketone (MIBK) (MIBK) solvent that gum resin (100 g) is scattered in 600 mL and at room temperature stir 60min.Insoluble gummy material passes through isolated by filtration.Utilize 2% potassium hydroxide solution (3*200 mL) repeatedly to extract MIBK solution to remove acid compound.In succession utilize subsequently water (400 mL) and salt solution (200 mL) washing MIBK layer.Under 70 ° of C decompressions of 60 –, evaporate MIBK layer, then under 110 ° of C of 75 – and high vacuum, volatile component is removed from oily residue, the boswellia serrata that obtains viscosity oily is set low polarity gum resin extract or BsLPRE(12 g).
Alternatively, the gum resin (250 g) of collecting from boswellia serrata tree utilizes methyl alcohol (300 mL*3) to extract and concentrate the methanolic extract of collecting.Residue (50 g) is dissolved in ethyl acetate (400 mL) and utilizes 1N potassium hydroxide (3 * 100 mL) extraction.Then water (2*200 mL) and salt solution (200 mL) washing organic layer evaporate to obtain frankincense oil.Under high vacuum and 75-110 ° of C, from described oil, evaporate volatile compound to obtain the BsLPRE of 22 g.
The solvent that uses the polarity from hexane to hexane/ethyl acetate mixture to ethyl acetate to strengthen to BsLPRE in standard silica gel chromatographic column.Based on the identical fraction set of TLC and using the fraction of set respectively repeatedly the mixture by utilizing hexane/ethyl acetate or hexane/acetone as the silicagel column of washing lotion to obtain pure compound.Thereby some impure fractions further obtain pure compound by the HPLC of anti-phase C18 silicagel column of preparation.By
1h nuclear magnetic resonnance,
13the structure of each compound of Analysis deterrmination of C nuclear magnetic resonnance, DEPT, HSQC and HMBC and a large amount of spectroscopic data, then compares the data of known compound and these data.Nine kinds of main compound that identify as shown in figure I are guiol (guiol) (1), nephthenol (nephthenol) (2), serratol (serratol) (3), diterpene X (diterpene X) (4), lupeol (lupeol) (5), olive-12-alkene-3 β-ol (olean-12-ene-3 beta-ol) (6), olive-12-alkene-3 α-ol (olean-12-ene-3 α-ol) (7), wool steroid-8, 24-diene-3 α-ol (lanosta-8, 24-diene-3 α-ol) (8) and Usu-12-alkene-3 α-ol (urs-12-ene-3 α-ol) (9).Then, adopt HPLC method to utilize these pure compounds to come standardization boswellia serrata to set low polarity gum resin extract (BsLPRE).As shown in table 1 to the discriminatory analysis of the new composition of BsLPRE based on HPLC and retention time (Rt) analytical method.
Embodiment 4:
the preparation of the low polarity gum resin of Ka Shi Boswellia carterii extract (BcLPRE):
Ka Shi Boswellia carterii gum resin (100 g) be scattered in methyl iso-butyl ketone (MIBK) (MIBK) solvent of 600 mL and at room temperature stir 60min.Insoluble gummy material passes through isolated by filtration.Utilize 2% potassium hydroxide solution (3*200 mL) repeatedly to extract MIBK solution to remove acid compound.In succession utilize subsequently water (400 mL) and salt solution (200 mL) washing MIBK layer.Under 70 ° of C decompressions of 60 –, evaporate MIBK layer, then under 85 ° of C of 75 – and vacuum, volatile component is removed from oily residue, obtain Ka Shi Boswellia carterii low polarity gum resin extract or the BcLPRE(9.5 g of viscosity oily).
Alternatively, the gum resin of collecting from Ka Shi Boswellia carterii (250 g) utilizes methyl alcohol (300 mL*3) to extract and concentrate the methanolic extract of collecting.Residue (50 g) is dissolved in ethyl acetate (400 mL) and utilizes 1N potassium hydroxide (3 * 100 mL) extraction.Then water (2*200 mL) and salt solution (200 mL) washing organic layer evaporate to obtain frankincense oil.Under vacuum and 75-85 ° of C, from described oil, evaporate volatile compound to obtain the BcLPRE of 17.75 g.
Embodiment 5
come from the bioavilability comparison of 3-O-acetyl group-11-ketone group-beta boswellic acid (AKBA) of different frankincense materials:
Isolation albefaction rat also selects healthy rat to be used for researching and analysing.The room that the animal of selection is placed in to distribution before 7 days of research beginning conforms.By the animal Random assignment for studying, to different processed group, overnight fasting is also freely drunk water, and records body weight and based on body weight, calculates the dosage of each animal.Before oral test sample and after oral 0.5, when 1.2.4.8 and 12 hours, collect the blood sample of all animals.By the blood sample grumeleuse gathering 10 minutes, and at 4 ℃ centrifugal 10 minutes of 1800g.Serum sample and 100 μ LTCA(20%) and 1.8mLHPLC level methyl alcohol deproteinized, 1800g is centrifugal 10 minutes at 4 ℃, the lcms analysis by supernatant for total AKBA.With the independent standardized 30%AKBA(LI13115 of boswellia serrata tree extract) (AUC:9.825) compare, containing the proportional tree of the boswellia serrata for 2:1 extract selectivity, be concentrated into 30%3-O-acetyl group-11-ketone group-beta boswellic acid (AKBA) (LI13115) and the composition LI13108F of boswellia serrata tree ethereal oil (BsLPRE); And demonstrating better oral administration biaavailability containing the composition LI13119F of the proportional tree standardized 30%AKBA of extract of the boswellia serrata for 2:1 and boswellia serrata tree steaming oil (BVOIL), area under a curve (AUC) is respectively 14.08 and 11.23.The bioavilability of LI13108F (with AUC opinion) exceeds LI13115 43.33%.The bioavilability of LI13119F exceeds LI13115 14.33%.In different time points different disposal treated animal, the serum-concentration of AKBA is as summed up in table 2.Serum-concentration and time diagram are as shown in figure II.
Embodiment 6:
the bioavilability comparison of LI01008 and its composition:
LI13124F1 animal conforms 7 days before research starts.Six animals are divided into two groups randomly, and every group comprises 3 animals.Record body weight and calculate dosage based on body weight.Utilize the dinor-curcumin (LI01008) of ratio that 450mg contains 2:1 and the LI01008 of composition BsLPRE(LI13115) (LI13124F1) or 300mg/kg as the oral feeding animals of the suspension in 0.5%CMC.At 0.5,1,2,4,6,8 and 12 time point mobile phone blood sample before and after treatment.The blood sample of mobile phone is processed in refrigerated centrifuge, utilizes HPLC level methyl alcohol to serum sample deproteinized, fully mixes and the centrifugal upper strata albumen of removing.Supernatant is used for the calculating of LI01008 by HPLC.Data are as shown in table 3.
Data demonstration, compares with taking separately LI01008, and the bioavilability of the LI01008 of composition LI13124F1 exceeds 75%.
Should understand, the change of these ordinary skills in the art can realize above-described embodiment and not deviate from scope of the present invention.Therefore, should be appreciated that described specific embodiment or example are not restrictions of the present invention, but in order to be encompassed in the clear and definite object of the present invention and the modification in scope.
Claims (2)
1. the purposes of a bio-enhancer, be selected from that the boswellia serrata that comes from gum olibanum fat is set former frankincense oil BsOIL, the fragrant ethereal oil BsVOIL of boswellia serrata tree milk and boswellia serrata is set low polarity gum olibanum fat extract B sLPRE or their mixture, for improving the bioavilability of biologic product.
2. the purposes of a kind of bio-enhancer as claimed in claim 1, described biologic product is the standardized 3-O-acetyl group-11-of dinor-curcumin, extract ketone group-beta boswellic acid.
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| PCT/IN2011/000364 WO2011151840A2 (en) | 2010-05-30 | 2011-05-26 | Compositions comprising non-acidic boswellia oil fraction as a bio-enhancer for enhancing the bioavailability of biological agents |
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| WO2018179011A1 (en) * | 2017-03-29 | 2018-10-04 | Olene Life Sciences Private Limited | Composition to enhance bioavailability of natural compounds |
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| US20080275117A1 (en) * | 2006-09-21 | 2008-11-06 | Dan Li | Compositions and Methods Comprising Boswellia Species |
| CN102711781A (en) * | 2010-02-15 | 2012-10-03 | 莱拉营养食品有限公司 | A novel boswellia low polar gum resin extract and its synergistic compositions |
| CN102811728A (en) * | 2010-03-15 | 2012-12-05 | 莱拉营养食品有限公司 | Boswellia oil, its fractions and compositions for enhancing brain function |
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| US20030228381A1 (en) * | 2001-07-20 | 2003-12-11 | Council Of Scientific And Industrial Research | Bioavailability enhancing activity of Carum carvi extracts and fractions thereof |
| ZA200602758B (en) * | 2003-09-26 | 2007-12-27 | Panacos Pharmaceuticals Inc | Novel triterpene derivatives, preparation thereof and use thereof |
| EP1765761B1 (en) * | 2004-06-18 | 2013-04-03 | Laila Nutraceuticals | Novel analogs of 3-o-acetyl-11-keto-beta-boswellic acid |
| CN101400359A (en) * | 2006-03-17 | 2009-04-01 | 草药科学新加坡私人有限公司 | Extracts and methods comprising curcuma species |
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| US20080275117A1 (en) * | 2006-09-21 | 2008-11-06 | Dan Li | Compositions and Methods Comprising Boswellia Species |
| CN102711781A (en) * | 2010-02-15 | 2012-10-03 | 莱拉营养食品有限公司 | A novel boswellia low polar gum resin extract and its synergistic compositions |
| CN102811728A (en) * | 2010-03-15 | 2012-12-05 | 莱拉营养食品有限公司 | Boswellia oil, its fractions and compositions for enhancing brain function |
Non-Patent Citations (2)
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| Basar S..Phytochemical Investigations on Boswellia Species.《Dissertation for the Fulfillment of the Requirements for the Degree of Dr. rer. nat.》.2005,第2-3、6、36页. * |
| Phytochemical Investigations on Boswellia Species;Basar S.;《Dissertation for the Fulfillment of the Requirements for the Degree of Dr. rer. nat.》;20051231;第2-3、6、36页 * |
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| CA2801157C (en) | 2019-07-16 |
| WO2011151840A3 (en) | 2012-01-26 |
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