CN1738632A - Bioavailability enhancing activity of carum carvi extracts and fractions thereof - Google Patents
Bioavailability enhancing activity of carum carvi extracts and fractions thereof Download PDFInfo
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Abstract
The present invention relates to the use of extracts of Carum carvi as bioenhancers, either alone or in combination with piperine or Zinzeber officinale extract to improve the bioavailability of a wide variety of drugs.
Description
Invention field
The present invention relates to bioavailability and/or biopotency reinforcing agent, be also referred to as the purposes of bio-enhancer or BE, and preparation method thereof, comprise it is separated and obtain its chemical characterization and the end product dactylogram form from natural origin.
The present invention relates to from plant caraway (Carum carvi), carry out the preparation of activity extract/part, comprise its chemical characterization, dactylogram drafting and utilize this class product to strengthen the bioavailability and/or the biopotency of medicine, natural product and basic nutrition thing.The present invention relates to the preparation of composite fortifier, this composite fortifier comprises polarity or nonpolar extract and/or the piperine (for example: Fructus Piperis (Piper nigrum) and Piper longum (Piper longum)) of Rhizoma Zingiberis Recens (Zingiber officinale), it can significantly increase the bioavailability of (50-180%) multiple medicament categories, such as but not limited to antibiotic, antifungal agent, antiviral agents, anticarcinogen, cardiovascular drug, central nervous system (CNS) medicine, anti-inflammatory/anti-arthritic, tuberculosis/antileprotic, antihistamine/respiratory distress disease medicine, corticosteroid, immunosuppressant, antiulcerative.Have been found that this class Fructus cari carvi extract/part that has or do not exist Rhizoma Zingiberis Recens and/or piperine (for example: Fructus Piperis and Piper longum) has the selectivity of height in its bioavailability/biopotency potentiation.
Background of invention
A large amount of medicines has its bioavailability is carried out improved medical need, and these medicines (a) biological utilisation is low, (b) long term administration, and (c) poisonous and price is high.Since after the oral drugs administration, the degree direct influence plasma concentration of bioavailability and follow-up curative effect and the relevant toxic action of dosage, and it is significant to treating therefore to maximize oral administration biaavailability.Because the major part of dosage does not arrive blood plasma or shows pharmacotoxicological effect, unless give heavy dose, however this can cause serious adverse, so still there is inferior therapeutic in the lower medicine of bioavailability.Any significant improvement of bioavailability will cause the reduction of certain drug dosage and the reduction of dosage number of times.In addition, the difference between the individuality is oppositely relevant with the size of bioavailability.Therefore low oral administration biaavailability causes higher diversity and relatively poor plasma concentration control and pharmacodynamic action.To having the medicine of narrower margin of safety, the difference between the individuality needs special concern.
Incomplete oral administration biaavailability has multiple reason.It comprises relatively poor dissolubility or lower water solublity, relatively poor intestinal mucosa permeability, intestinal or liver metabolism in gastric juice or intestinal juice before degraded and the system.The solution wherein common way of some problem is aforesaid increase dosage, and this can produce the toxic action that the patient does not comply with.
In therapeutic process, many therapeutic are disposed and also are attended by losing of basic nutrition thing.The present invention also comprises that by increase the various nutraceutical bioavailability/biopotency of metal and vitamin improves nutritional status.Because multiple reason, bio-enhancer of the present invention also has the biopotency that strengthens medicine and the probability that does not influence its plasma concentration, wherein partly cause is described in " bioavailability/biological enhanced activity " of the present invention part, but is not limited to these reasons.The description of association area
Taked some approach to maximize oral administration biaavailability in the past, for example (a) reduces granular size (micronization, nanorize or the like), (b) selection of pleomorphism or crystal size and form, (c) come the lower medicine of dissolubility is carried out solubilising by chemical modification, complexation, use cosolvent/surfactant, (d) carry out the targeting transmission of medicine at action site, (e) transmission by film bag quilt or use polymeric matrices control medicine comes slow releasing pharmaceutical, (f) prodrug approach, and (g) utilize liposome to carry out microencapsulation.
Yet according to the clue of Ayurvedic document, the new way that increases the bioavailability of medicament comprise the medicine that bioavailability is lower is at RRL, conceptualization among the Jammu.One of them is " Trikatu " for these medical herbs group, and it often is recorded the essential part (about 70%) as the Ayurvedic prescription, and it comprises three kinds of pungent product, i.e. long Fructus Piperis, black pepper and the Rhizoma Zingiberis of equal portions.Discovery is the reason of bioavailability potentiation from piperic main alkaloid component (piperine).The effect of Rhizoma Zingiberis Recens is to regulate function of intestinal canal to promote to absorb.Extensively carried out the research of piperine for anti-TB drug influence.Prove that uniting use with piperine, that the dosage of rifampicin is reduced is about 50%, has kept the treatment effectiveness of this anti-TB medicine under standard dose (450mg) simultaneously.Find according to these, other several well-known plants have been carried out bioavailability/biopotency enhanced activity evaluation.Some plant parts are the polarity of Rhizoma Zingiberis Recens and Cuminum cyminum L (Cuminum cyminum) and the bioavailability that nonpolar extract significantly increases (25-300%) multiple medicament categories, and these medicines are such as but not limited to such as but not limited to antibiotic, antifungal agent, antiviral agents, anticarcinogen, cardiovascular drug, CNS medicine, anti-inflammatory/anti-arthritic, anti-TB/ antileprotic, antihistamine/respiratory disease disease drug, corticosteroid, immunosuppressant, antiulcerative.Have been found that this extract that has or do not exist piperine has the selectivity of height in its bioavailability/biopotency potentiation.
Caraway is a kind of medical herbs for cooking, and is extensive use of in India.Often mention this medical herbs being used for multiple uncomfortable Ayurvedic and other India medicine prescription system.Single plant can remain a scientific mystery to like this multiple discomfort or the disease biologically active that is suitable for these prescriptions.
The chemical property of caraway
Caraway (Carum carvi Linn) seed is called Jira (Beng.), Shahjiru (Guj.), Kalajira, Shiajira (Hindi), Shalajira (Mar.).Caraway is annual or gave birth in 2 years and do not have the hair herbaceous plant, the 30-100cm height, originate in Europe and West Asia, find to have grows wild, and have plantation to be used for producing aromatic seed on the hills of north India and the hills of Plain and South India at Himachal Pradesh.
The seed of this kind of plant is widely used as the flavoring agent of cooking purpose and bread, cookies, cake, confection, cheese, curry, curing food, sausage, meat products, preserve and the seasoning of kummel type sweet wine.It also can be used as the flavor ingredients in analeptic and the specific hashish.In medicine, it is used as antiflatulent, demulcent gastrotonica, fragrance and diuretic.Its seed and lard oil (Pueraria lobota thread seed oil (caraway oil)) are all arranged in flatulence angor and the disorderly prescription of stomach.Lumbago and rheumatisant's ill part is exposed in the steam of this seed and can alleviates this disease.The alcohol extract of this fruit shows dose-dependent spasmolytic effect.Find that its water can be as the carrier of pediatric medicament.And the hexane extract of finding this fruit has outstanding insecticidal action [Marketing of Minor Spices in India, 1968,119 to culex (Culex pipiensfatigans Wiedm.); Krishna ﹠amp; Badhwar, J.Sci. Industr.Res., 1952,11A, suppl., 259; Sharma and Kapil, Loc.cit.; Embong et al Canad J Pl Sci., 1977,57,543; I.P., 1966,104; I PC., 55; Gharat, Pharmaceutist, 1958-59,4 (2), 21; Cappelletti et al., J.Ethnopharmacol, 1982,6,178; Forster et al, Planta Med, 1980,40,309; Deshmukh et al, Pesticides, 1982,16 (12), 7].Dried this class seed of milling obtains having the light yellow lard oil to light brown of aromatic odor (being called Pueraria lobota thread seed oil) by force with steam distillation.Its oil content of maturity according to this class seed has difference.Storage is 2.8 percentage points at the most of every year to the influence of the oil content of this class seed.All India's samples of this class seed contain the Pueraria lobota thread seed oil of 5.8-8.1%.Carvone (Carvone) and limonene (limonene) are this oily key components and are the main sources of its abnormal smells from the patient and fragrance.Other component that exists in this oil comprises α-and β-sobrerone and ρ-cymol.Except that said components, from European Pueraria lobota thread seed oil, also separate and obtained camphene, Δ 3-carene, dihydro carvone, β-fenchene, myrcene, α-and β-phellandrene, sabinene, α-and γ-terpinene, α-limonene, terpinolene, tricyclene, d-and 1-dihydro pinol, the new dihydro carveol of 1-(neodihydrocarveol), the different dihydrocarveol of 1-(isodihydrocarveol), carveol (carveol), d-dihydrocarveol, acetaldehyde, methanol, furfural (Arctander, 124; Dijkstraand Speckmann, loc. cit.; Atal ﹠amp; Sood, Indian J Pharm, 1967,29,42; I.P., 1966,105; Padha et al Parfum u Kosmetik, 1969,50,296; Chem Abstr. 1980,93,191892; Salveson ﹠amp; Svendsen, Planta Med.1976,30,93, Guenther, IV, 582).
Pueraria lobota thread seed oil as Fructus cari carvi seed is used for seasoning some food at first, and be used as the aerofluxus medicine in medicine.It is the main component in Scandinavia " gin (Schnapps) " and the Germany " kummel (kummel) ".It also is used for the preparation of collutory, the flavoring agent of toothpaste, chewing gum, confection and as the pharmaceutical preparation of bad smell and the masking reagent of unpleasant insecticide.It also shows has a liking for neural spasmolytic activity.With the mixture of pure and mild Semen Ricini (castor) oil in, it is used for the treatment of scabies.This lard oil shows demulcent antibacterium and antifungal property to some antibacterials and fungus.Taking off carveol oil (Decarvonised oil) sells on market to cheap soap and tarts up and be used in semipervine and Nicotiana tabacum L. (tabac) spice (IPC., 54; Arctander, 125; Chopra et al, 1958,92; Chem Abstr, 1968,68,48218; Narayan et al IndianDrugs, 1979-80,17,394; El-keltawi et al, Herba pol, 1980,26,245).
Described seed also contains 3-glucoside and 3-galactoside, quercetin (quercetin) and isorhamnetin (isorhamnetin) and the carbon compound (mp, 62-63 °) of kaempferol (kaempferol).Also relevant for there being 5-methoxyl group-and the report of 8-methoxypsoralen (psoralens), sterol, umbelliferone (umbelligerone), scopoletin (scopoletin) and ayapanin (hemiarin).The aliphatic acid composition of described oil is: Petiolus Trachycarpi oil, 3.6; Oil, 60.7; Liholeic, 19.6 and petroselinic, 17.0% (Food technol Abstr., 1974, No.93,470; Harborne ﹠amp; Williams, Phytochemistry, 1972,11,1741; Ceska et al., ibid, 1987,26,165; Chakraborti, Trans Bose Res Inst, 1956-58,21,61; Chem.Abstr., 1969,71,57561; Hilditch ﹠amp; Williams, 287).
United States Patent (USP) the 5th, 7441, the compositions that discloses based on ginger-root extract for No. 161, but use as bio-enhancer.In addition, piperine only has activity to some drugs, and the other medicines in the identical treatment classification are not had or have only edge action.For example, for anti-TB and leprosy medicine, piperine demonstrates the enhanced level of statistics remarkable (p, 0.01) and highly significant (＜0.001) respectively to dapsone and rifampicin.Yet it does not have isoniazid, pyrazinamide and ethambutol or only marginate biological potentiation.Similarly, piperine can not strengthen the level such as the oral antidiabetic drug (hypoglycaemics) of tolbutamide (tolbutamide), chlorpropamide (chlorpropamide).
Goal of the invention
Main purpose of the present invention provides the bioavailability enhancing composition, and it comprises the extract/part of caraway at least.
Another object of the present invention provides the bioavailability enhancing composition, and it utilizes Fructus cari carvi extract/part and one of Fructus Piperis and Rhizoma Zingiberis Recens or both extract/parts.
A further object of the present invention provides the bioavailability enhancing composition, and it is the complex of the extract of caraway, Fructus Piperis and Rhizoma Zingiberis Recens.
Summary of the invention
In view of the above, the invention provides the Fructus cari carvi extract and/or biologically-active moiety and the healing potion that comprise as the effective dose of bioavailability reinforcing agent, and contain additive or carrier arbitrarily.
The present invention also provides the caraway water extract that comprises effective dose or the compound bio reinforcing agent of biologically-active moiety and at least a other bio-enhancer, and it is used to strengthen the bioavailability of medicine, dietetic product (neutraceutical), vitamin, antioxidant, natural herbal product and basic nutrition composition.
In one embodiment of the invention, described at least a other bio-enhancer is selected from piperine and Rhizoma Zingiberis Recens extract.
The present invention also provides the treatment combination of agents that comprises Fructus cari carvi extract, its part or its mixture, piperine and treatment effective dose thing, and described treatment reagent is selected from antibiotic, antibacterial, antifungal, antiviral agent, anti-tuberculosis agents, leprosy medicament, anti-inflammatory/arthritis medicament, cardiovascalar agent, antihistamine medicament, CNS medicine, respiratory distress abirritant, immunosuppressant, antiulcer agents, nutritional preparation and herbal medicinal product.
Described bio-enhancer preferably uses with the water extract of caraway or 50% alcohol extract or its part or its mixture.The effective dosage ranges of used bio-enhancer extract is the 5-100mg/Kg body weight.The dosage range of used caraway active part is 1-55mg.
Described antibiotic is selected from fluoroquinolones, Macrolide, cephalosporins, penicillins and aminoglycoside.Described fluoroquinolones is selected ciprofloxacin, norfloxacin, ofloxacin and norfloxacin.Described Macrolide is selected from erythromycin, Roxithromycin and azithromycin.Described cephalosporins is selected from cefadroxil, cephalo Qu Tai, cefixime and cefidinir.Described penicillins is selected from amoxicillin and cloxacillin, and described aminoglycoside is selected from amikacin and kanamycin.Described antifungal is selected from fluconazol, amphotericin B and ketoconazole.Described anticarcinogen is selected from methotrexate and 5-fluorouracil.Described cardiovascalar agent is selected from lisinopril (lisinopril), atenolol and propranolol.Described antiviral agent is selected from acyclovir (acyclovir) and zidovudine (zidovudine).Used CNS medicine is haloperidol (haloperidol).Described anti-inflammatory/arthritis medicament is selected from nimesulide (nimesulide) and rofecoxib (rofecoxib).Described anti-TB/ leprosy medicament is selected from rifampicin, pyrazinamide, dapsone, second sulfur isoniazid (etionamide) and cycloserine.
Described antihistamine/respiratory disease disease drug is selected from salbutamol, theophylline, bromhexine (Bromhexine) and loratadine (loratidine).Described corticosteroid is selected from andrographolide, dexamethasone and betamethasone.Described immunosuppressant is selected from cyclosporin A and tacrolimus (tacrolimus).Described antiulcer agent is selected from ranitidine, cimetidine and omeprazole (omeprazole).Described herb extracts is selected from Tinosooracordifolia (Tinospora corddifolia), Rhizoma Picrorhizae (Picrorrhizakurroa), baelfruit (Aegles marmelos), Herba Andrographis (Andrographis paniculata), Fructus Chebulae's (ARULA) (Terminalia chebula), Herba Asari fecula (Withania somnifera) and collapses the extract of jorum (Centella asiatica).Described nutritional preparation is selected from vitamin, antioxidant, natural herbal product and basic nutrition component.
Described vitamin is selected from vitamin A, vitamin E, vitamin B
6, vitamin B
12, vitamin C and folic acid.Described antioxidant is selected from bata-carotene, silymarin and selenium.Described basic nutrition composition is selected from methionine, leucine, lysine, valine, isoleucine, zinc, calcium, glucose, potassium, copper and ferrum.
Described compositions can be outer by oral, intestinal, the administration of intranasal, the suction that comprises spray, rectum, vagina and transdermal.Described antibiotic dosage range is 10-55mg/kg, and the dosage range of antifungal is 50-80mg/kg; The dosage range of anticarcinogen is 5-30mg/kg; The dosage range of cardiovascular drugs is 0.5-10mg/kg; The dosage range of antiviral agent is 10-50mg/kg; The dosage range of CNS medicine is 0.1-0.5mg/kg; The dosage range of anti-inflammatory/arthritis medicament is 2-10mg/kg; The dosage range of the medicine of anti-TB/ leprosy is 10-75mg/kg; The dosage range of antihistamine/respiratory medications is 0.5-30mg/kg; The dosage range of glucocorticoid is 0.05-5mg/kg; The dosage range of immunosuppressant is 5-15mg/kg.The dosage range of antiulcer agent is 2-45mg/kg.The dosage range of described vitamin is 0.1mg/kg-40mg/kg.The dosage range of described antioxidant is 5-15mg/kg.Described basic nutrition dose of components scope is 20-55mg/kg.The dosage range of described herb extracts is 10mg/kg-1g/kg.
Bioavailability/biopotency enhanced activity
The present invention relates to separation and Extraction thing and/or its part from the plant caraway, and in advance as the standardization of the purposes of drug bioavailability and/or biopotency reinforcing agent, described medicine belongs to such as antibacterial, antifungal, antiviral agent, antitubercular agent, antileprotic, anti-inflammatory/anti-arthritic, cardiovascular drug, antihistaminic, the respiratory distress abirritant, immunosuppressant, antiulcer agent, the therapeutic agent classification of dietetic product but be not limited thereto, described medicine are used in compositions at people and/or veterinary disease by outside oral/intestinal, local, intranasal, suck (comprising spray), rectum, the administration of vagina mode.
The invention still further relates to the preparation of the preparation of the extract that contains the plant caraway and/or its part and piperine, the standardization of drug bioavailability and/or biopotency reinforcing agent purposes, described medicine belongs to such as antibacterial, antifungal, antiviral agent, antitubercular agent, antileprotic, anti-inflammatory agent, anti-arthritic, cardiovascular drug, antihistaminic, the respiratory distress abirritant, immunosuppressant, antiulcer agent, the therapeutic agent classification of dietetic product but be not limited thereto, described medicine are used in compositions at people and/or veterinary disease by outside oral/intestinal, local, intranasal, suck (comprising spray), rectum, the administration of vagina mode.
The invention still further relates to the preparation of the preparation of the extract that contains plant caraway and Rhizoma Zingiberis Recens and/or its part, and and in advance as the standardization of drug bioavailability and/or biopotency reinforcing agent purposes, described medicine belongs to such as antibacterial, antifungal, antiviral agent, antitubercular agent, antileprotic, anti-inflammatory agent, anti-arthritic, cardiovascular drug, antihistaminic, the respiratory distress abirritant, immunosuppressant, antiulcer agent, the therapeutic agent classification of dietetic product but be not limited thereto, described medicine are used in compositions at people and/or veterinary disease by outside oral/intestinal, local, intranasal, suck (comprising spray), rectum, the administration of vagina mode.The composition of described bioavailability/biopotency reinforcing agent can be any extract, its part or the pure molecule that derives from described plant.Medicine can at random be selected from the therapeutic agent classification such as said medicine.
The method of prepared plant extracts/part comprises combination, halogenated hydrocarbons, ketone, the ether that makes water, alcohol, water and alcohol.Described plant can comprise the plant that contains piperine.The compound bio reinforcing agent that contains the activity extract/part that derives from caraway and/or Rhizoma Zingiberis Recens and contain or do not contain piperine of the present invention utilizes as the physical technique of dialysis/molecular sieve/film, plurality of color spectral technology and/or liquid-liquid or solid phase extractions, and subsequently to its completely finger printing identify (HPLC/HPTLC/LC-MS-MS).The simple physics mixing is not represented in the combination that contains the bio-enhancer of activity extract/part, and expression is used for preparation purpose ad hoc approach, it can adopt chemical technology, as reducing granular size, use selectivity polarization reagent or using ion/non-ionic surface active agent.That the combination that is selected from the pharmaceutical preparation of therapeutic agent classification of described medicine, nutritional preparation, medical herbs/preparation and described bio-enhancer can be used for is for example oral, intestinal outer, intranasal, the suction that comprises spray, rectum, vagina, transdermal and other administering mode.
Extract/the part of caraway use separately or with biological potentiation that Rhizoma Zingiberis Recens extract/part and/or piperine make up be selectively, such as but not limited to appended embodiment, and can not strengthen the bioavailability/biopotency of every kind of medicine, nutritional preparation, medical herbs/preparation.
Described plant extract/in its used dosage range, do not show when part is used alone or in combination itself biology or toxicology effect.
With the medicine of different therapeutic agent classifications and nutritional preparation (essential amino acids, metal, antioxidant, vitamin) and medical herbs water, water-alcohol, ketone, ether, the halogenated solvent extract of described plant part are estimated.Bioavailability/biopotency enhancing (BE) activity of finding Fructus cari carvi extract is consistent in the scope of 5mg-100mg, and irrelevant with the medicament contg in the described preparation.With identical drug categories, the inferior part of activity extract is also estimated.It is 1.0-55mg that described part produces the active dosage range of BE.Discovery all can play a role when female extract and described active part make up separately and mutually for different drug categories.
Find when with exploitation when the bio-enhancer product of Rhizoma Zingiberis Recens is united use, the described independent extract or the activity of its part have increased 20-110%.Effective BE scope of Rhizoma Zingiberis Recens is 10-150mg.In addition, female extract of the caraway of various combination and part thereof demonstrate the obvious activity of 25-95% in the presence of piperine.Content of piperine scope in these preparations is 3-15mg.
Find no matter to be with or without the biological potentiation from Rhizoma Zingiberis Recens and/or piperine, described extract or its part have the selectivity of height in its bioavailability and/or biopotency enhanced activity.As the exemplary ground that provides among the appended embodiment, can obviously find out this selectivity bioavailability that causes from these extract/parts and/or the biopotency enhancing degree.
The reason of this selective mode can be summed up as following one or more factors: (a) promote the absorption of medicine from GIT, (b) inhibition or reduction medicine are in the biotransformation speed of liver or intestinal, (c) regulating the feasible aggregate demand to described medicine of immune system reduces substantially, (d) increase permeability or inlet, even it can become persistent agent having a liking at Mycobacterium tuberculosis and other this type of bacterium huge in the cell to pathogen.
This can finally guarantee to kill these organisms very safely in described position, rather than do not reach described active medicine, (e) suppress the ability that pathogen or abnormal structure resist described medicine, antimalarial for example, the outer stream mechanism that anticarcinogen and antimicrobial drug often run into, (f) signal processing of regulating between host and pathogen guarantees the accessibility of described medicine to described pathogen, (g) strengthen in described medicine and the pathogen such as albumen, DNA, the combination of the receptor of RNA etc., thereby strengthen and prolong the enhanced antibiotics activity of its effect generation thus at pathogen, (h) be close to the rational activation pattern except that above-mentioned, described biological reinforced dose also can be used for promoting nutrient and described medicine to stride the transfer of blood brain barrier, and it is to infecting such as brain, the control of epilepsy and other CNS disease has good assosting effect.
First and foremost, but do not get rid of, the medicine that the present invention strengthens in the carrier mediated tissue enters and passive diffusion and active transport approach, and it is responsible for the physiologically substance transhipment such as nutritional preparation is entered its target position.Because of being applicable to any mechanism of action, product of the present invention provides with collaborative and/or additional mode, thereby make described most drug in this area and nutritional preparation in the presence of described product, as the result who is produced by one or more these mechanism, its bioavailability or biopotency improve.
Except that important to the mankind, the bioavailability of medicine and nutritional preparation and/or biopotency are also relevant with the health of animal.Therefore the present invention also is used for veterinary formulation.
Different extracts be separated into manifold step shown in following flow chart.
The preparation flow figure of plant Rhizoma Zingiberis Recens extract
The caraway water extract is separated into manifold flow chart
The preparation of plant Fructus cari carvi extract
Following embodiment exemplarily is illustrated certain preferred embodiments, should not be construed as limitation of the scope of the invention.
Table 1: be used for the tabulation of some exemplary agents of the object of the invention
| Classification | Medicine | |
| I | Antibiotic | Fluoroquinolones: ciprofloxacin, norfloxacin, the P-Flucloxacillin, ofloxacin Macrolide: erythromycin, Roxithromycin and azithromycin cephalosporins: cefixime, cefalexin, cefadroxil, cephalo Qu Taihe cefidinir penicillins: amoxicillin and cloxacillin aminoglycoside: amikacin and kanamycin |
| II. | Antifungal | Fluconazol, amphotericin B and ketoconazole |
| III. | Antiviral agent | Acyclovir, zidovudine |
| IV. | Anticarcinogen | Methotrexate, 5-fluorouracil, Dauxorubicin, cisplatin, daunorubicin |
| V. | The CVS medicine | Amlodipine, lisinopril, atenolol |
| VI. | The CNS medicine | Alprazolam, haloperidol |
| VII. | The anti-inflammatory anti-arthritic | Diclofenac, piroxicam, nimesulide and rofecoxib |
| VIII | Anti-TB/ antileprotic | Rimactazid, pyrazinamide, ethambutol, dapsone |
| IX. | Antihistamine/breathing disease | Albuterol, theophylline, bromhexine, Loretidine |
| X. | Corticosteroid | Prednisone, dexamethasone, betamethasone |
| XI. | Immunosuppressant | Cyclosporin A, tacrolimus, mofetil enzyme phenolic acid ester |
| XII | Antiulcerative | Ranitidine, cimetidine, omeprazole |
In all following forms, the bio-enhancer of caraway comprises its water extract or 50% alcohol extract or part 1.The bio-enhancer of Rhizoma Zingiberis Recens is represented 50% alcohol extract of fresh ginger.No matter described bio-enhancer separately or unite use, described dosage remains unchanged.
Embodiment 1
The content of used bio-enhancer is as follows:
I. from caraway: extract 30mg/kg body weight (rat); Part 1:15mg/kg body weight (rat)
Ii. piperine: 8mg/kg body weight (rat)
Iii. Rhizoma Zingiberis Recens: 35mg/kg body weight (rat)
Used medicine is rifampicin (40mg/kg).This medicine is united the rat administration separately or with described bio-enhancer in such a way:
Group 1: matched group
Group 2: independent rifampicin
Group 3: independent bio-enhancer
Group 4: rifampicin and caraway bio-enhancer
Blood (0-24 hour) (totally 14 times) default interval collection contrast/processing animal.Utilize dichloromethane from described blood (slurry), to extract rifampicin.Utilize HPLC (model: Shimadzu 1080 BP); The PDA detector is measured the rifampicin concentration in the described sample.Mobile phase is the phosphate buffer of 40: 60 ratios: acetonitrile, flow are 1.0ml/min.
Embodiment 2
At the same approach in different medicine employing the foregoing descriptions 1.See following table for details:
(i) antibiotic
(a) fluoroquinolones
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Ciprofloxacin | 45 | 78 | 55 | 110 | 68 | 133 |
| The P-Flucloxacillin | 40 | Do not have | 61 | 70 | 53 | 75 |
| Ofloxacin | 20 | 65 | 52 | 167 | 49 | 170 |
| Norfloxacin | 40 | 55 | Do not have | 65 | Do not have | 60 |
(b) Macrolide
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Erythromycin | 45 | 70 | 95 | 100 | 68 | 105 |
| Roxithromycin | 15 | 65 | 110 | 95 | 72 | 98 |
| Azithromycin | 25 | 55 | 89 | 90 | 78 | 86 |
(c) cephalosporins
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Cefalexin | 45 | Do not have | 90 | 90 | 75 | 79 |
| Cefadroxil | 45 | 67 | 70 | 95 | 68 | 85 |
| Cephalo Qu Tai | 25 | 72 | Do not have | 78 | Do not have | 75 |
| Cefixime | 40 | 80 | Do not have | 79 | Do not have | 82 |
| Cefidinir | 40 | 89 | 60 | 95 | 35 | 130 |
(d) penicillins
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Amoxicillin | 45 | 75 | 120 | 115 | 80 | 100 |
| Cloxacillin | 25 | 110 | 87 | 95 | 76 | 110 |
(e) aminoglycoside
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Amikacin | 50 | 85 | Do not have | 100 | Do not have | 92 |
| Kanamycin | 50 | Do not have | 72 | 87 | 65 | 68 |
(ii). antifungal
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Fluconazol | 65 | 65 | 87 | 98 | 120 | 110 |
| Amphotericin B | 78 | 78 | Do not have | 90 | Do not have | 80 |
| Ketoconazole | 55 | 55 | 105 | 100 | 125 | 96 |
(iii) anticarcinogen
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Methotrexate | 5 | 76 | 65 | 89 | 87 | 102 |
| 5-fluorouracil | 25 | 90 | 87 | 110 | 110 | 100 |
| Dauxorubicin | 5 | Do not have | 68 | 70 | 72 | 69 |
| Cisplatin | 5 | Do not have | Do not have | Do not have | 56 | 55 |
(iv) cardiovascular drug
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Amlodipine | 1.0 | Do not have | 43 | 50 | 68 | 65 |
| Lisinopril | 1.0 | 79 | 85 | 95 | 76 | 90 |
| Atenolol | 5 | 100 | Do not have | 93 | Do not have | 97 |
| Propranolol | 8 | 68 | 84 | 90 | 76 | 75 |
(v) antiviral agents
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Acyclovir | 40 | 78 | 96 | 100 | 82 | 90 |
| Zidovudine | 10 | 92 | 140 | 95 | 105 | 87 |
(vi) CNS medicine:
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Alprazolam | 0.1 | Do not have | 65 | 70 | 76 | 80 |
| Haloperidol | 0.5 | 95 | Do not have | 90 | Do not have | 85 |
(vii) anti-inflammatory/arthritis medicine:
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Diclofenac | 5 | Do not have | 120 | 100 | 90 | 95 |
| Piroxicam | 2 | Do not have | 110 | 98 | 86 | 76 |
| Nimesulide | 10 | 100 | 132 | 140 | 144 | 145 |
| Rofecoxib | 2.5 | 75 | Do not have | 70 | Do not have | 80 |
(viii) anti-TB/ antileprotic:
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Rifampicin | 40 | 110 | 45 | 170 | 65 | 140 |
| Isoniazid | 25 | Do not have | Do not have | Do not have | Do not have | Do not have |
| Pyrazinamide | 12.5 | 45 | Do not have | 50 | Do not have | 55 |
| Ethambutol | 70 | Do not have | Do not have | Do not have | Do not have | Do not have |
| Dapsone | 10 | 56 | 34 | 67 | 46 | 68 |
| Second sulfur isoniazid | 25 | 68 | 45 | 65 | 56 | 70 |
| Cycloserine | 40 | 70 | 67 | 80 | 71 | 75 |
(ix). antihistamine/respiratory disease disease drug:
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Albuterol (Salbutarnol) | 0.8 | 75 | 60 | 89 | 78 | 80 |
| Theophylline | 30 | 70 | 65 | 79 | 76 | 89 |
| Bromhexine | 25 | Do not have | 67 | 70 | 67 | 71 |
| Loratidine | 1.0 | 76 | Do not have | 70 | Do not have | 80 |
(x) corticosteroid:
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Prednisone | 4 | 65 | Do not have | 67 | Do not have | 60 |
| Dexamethasone | 0.05 | 72 | 66 | 77 | 76 | 73 |
| Betamethasone | 0.1 | 80 | 72 | 89 | 75 | 77 |
(xi) immunosuppressant:
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Cyclosporin A | 10 | 100 | Do not have | 105 | 116 | 120 |
| Tacrolimus | 5 | 90 | 105 | 95 | 75 | 114 |
| Mofetil enzyme phenolic acid ester | 15 | Do not have | Do not have | Do not have | Do not have | Do not have |
(xii) antiulcerative
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Ranitidine | 30 | 67 | 21 | 70 | 147 | 150 |
| Cimetidine | 40 | 72 | Do not have | 84 | 98 | 100 |
| Omeprazole | 2 | 76 | Do not have | 70 | Do not have | 75 |
D. Chinese medicine preparation
| Dosage mg/kg | Biological utilisation enhanced level % | |||||
| BE from caraway | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | ||
| Feverfew Echinacea (Echinacea Augustifolia) | 10 | Do not have | 75 | 76 | 66 | 65 |
| Tinosooracordifolia | 50 | 76 | 85 | 90 | 67 | 71 |
| Rhizoma Picrorhizae | 50 | 80 | 78 | 110 | 56 | 76 |
| Baelfruit | 1000 | 65 | Do not have | 65 | Do not have | 60 |
| Herba Andrographis | 50 | 68 | 63 | 72 | 55 | 54 |
| Emblica ribes | 50 | Do not have | Do not have | Do not have | 65 | 68 |
| Asparagus racemosus (Asparagus racemosus) | 50 | Do not have | 58 | 55 | 44 | 45 |
| The Fructus Chebulae | 50 | 92 | Do not have | 87 | Do not have | 91 |
| The Herba Asari fecula | 60 | 76 | 55 | 70 | 64 | 76 |
| Collapse jorum | 30 | 68 | Do not have | 65 | Do not have | 62 |
E. nutritional preparation
| Dosage mg/kg | Biological utilisation enhanced level % | ||||||||
| Caraway (Cc) | Piperine is as BE | Caraway+piperine | BE from Rhizoma Zingiberis Recens | Caraway+Rhizoma Zingiberis Recens | |||||
| Extract | Part 1 | Extract (Cc) | Part 1 (Cc) | Extract (Cc) | Part 1 (Cc) | ||||
| Vitamin | |||||||||
| Vitamin A | 1mg | 17 | 19 | 11 | 13 | 16 | Do not have | 20 | 27 |
| Vit E | 40mg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Vit B 1 | 10mg | 37 | 42 | 17 | 21 | 26 | 31 | 43 | 55 |
| Vit B 6 | 0.5 | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Vit B 12 | 0.1μg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Vit C | 50mg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Folic acid | 50μg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Antioxidant | |||||||||
| Bata-carotene | 15mg | 47 | 55 | 29 | 45 | 59 | 35 | 63 | 72 |
| Silymarin | 5mg | 31 | 38 | Do not have | 36 | 45 | 33 | 38 | 41 |
| Selenium | 2μg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| The natural herbal product | |||||||||
| Rhizoma Curcumae Longae | 50mg | 40 | 48 | 39 | 42 | 51 | 49 | 43 | 52 |
| Boswellic acid (Boswellic acids) extract | 50mg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Rutin | 40mg | 34 | 45 | 33 | 36 | 40 | 42 | 34 | 42 |
| The basic nutrition composition | |||||||||
| Methionine | 20mg | 20 | 28 | 11 | 25 | 30 | 23 | 30 | 37 |
| Lysine | 40mg | 26 | 29 | 31 | 33 | 38 | 19 | 39 | 43 |
| Leucine | 50mg | 19 | 21 | 22 | 29 | 32 | 24 | 35 | 40 |
| Valine | 25mg | 16 | 19 | Do not have | 22 | 29 | 21 | 32 | 38 |
| Isoleucine | 25mg | 28 | 34 | 16 | 37 | 44 | 15 | 42 | 50 |
| Zinc * | 0.1mg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Calcium * | 30mg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Glucose | 50mg | 28 | 31 | 35 | 41 | 50 | 13 | 37 | 46 |
| Potassium * | 25mg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Copper * | 30mg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
| Ferrum * | 0.5mg | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have | Do not have |
*Dosage is equivalent to constituent content
Claims (62)
1. Bioenhanced compositions, it comprises the Fructus cari carvi extract and/or the biologically-active moiety as the biological utilisation reinforcing agent of effective dose, and healing potion, and comprises additive or carrier arbitrarily.
2. compound bio reinforcing agent, it comprises the caraway water extract or the biologically-active moiety of effective dose, and at least a other bio-enhancer that is used to strengthen the bioavailability of medicine, nutritional preparation, vitamin, antioxidant, natural herbal product and basic nutrition composition.
3. compound bio reinforcing agent as claimed in claim 2, wherein said at least a other bio-enhancer is selected from piperine and Rhizoma Zingiberis Recens extract.
4. compositions as claimed in claim 1, it comprises the therapeutic agent of Fructus cari carvi extract, its part or its mixture, piperine and treatment effective dose, and described healing potion is selected from antibiotic, antibacterial, antifungal, antiviral agent, tuberculosis, antileprotic, anti-inflammatory/arthritis medicament, cardiovascalar agent, antihistamine medicament, CNS medicine, respiratory distress abirritant, immunosuppressant, antiulcerative, nutritional preparation, herbal medicinal product.
5. compositions as claimed in claim 1 or 2, wherein used bio-enhancer are water extract or 50% alcohol extract or its part or its mixture that is derived from caraway.
6. compositions as claimed in claim 1 or 2, the effective dosage ranges of wherein used bio-enhancer extract is the 5-100mg/Kg body weight.
7. as claim 1,2 or 4 described compositionss, the dosage range of wherein used caraway active part is 1-55mg.
8. compositions as claimed in claim 4, wherein said antibiotic is selected from fluoroquinolones, Macrolide, cephalosporins, penicillins and aminoglycoside.
9. compositions as claimed in claim 8, wherein said fluoroquinolones is selected from ciprofloxacin, ofloxacin and norfloxacin.
10. compositions as claimed in claim 8, wherein said Macrolide is selected from erythromycin, Roxithromycin and azithromycin.
11. compositions as claimed in claim 8, wherein said cephalosporins are selected from cefadroxil, cephalo Qu Tai, cefixime and cefidinir.
12. compositions as claimed in claim 8, wherein said penicillins is selected from amoxicillin and cloxacillin.
13. compositions as claimed in claim 8, wherein said aminoglycoside are selected from amino hydroxyl butyl kanamycin and kanamycin.
14. compositions as claimed in claim 4, wherein said antifungal is selected from fluconazol, amphotericin B and ketoconazole.
15. compositions as claimed in claim 4, wherein said anticancer agent is selected from methotrexate and 5-fluorouracil.
16. compositions as claimed in claim 4, wherein said cardiovascalar agent is selected from lisinopril, atenolol and propranolol.
17. compositions as claimed in claim 4, wherein said antiviral agent is selected from acycloguanosine acyclovir and zidovudine.
18. compositions as claimed in claim 4, wherein used CNS medicine is a haloperidol.
19. compositions as claimed in claim 4, wherein said anti-inflammatory/arthritis medicament is selected from nimesulide and rofecoxib.
20. compositions as claimed in claim 4, wherein said anti-TB/ leprosy medicament is selected from rifampicin, pyrazinamide, dapsone, second sulfur isoniazid and cycloserine.
21. compositions as claimed in claim 4, wherein said antihistamine/breathing disease medicament is selected from salbutamol, theophylline and bromine hexylamine and loratadine.
22. compositions as claimed in claim 4, wherein said corticosteroid medicament is selected from andrographolide, dexamethasone and betamethasone.
23. compositions as claimed in claim 4, wherein said immunosuppressant is selected from cyclosporin A and tacrolimus.
24. compositions as claimed in claim 4, wherein said antiulcer agents is selected from ranitidine, cimetidine and omeprazole.
25. compositions as claimed in claim 4, wherein said herb extracts are selected from Tinosooracordifolia, Rhizoma Picrorhizae, baelfruit, Herba Andrographis, Fructus Chebulae, Herba Asari fecula and collapse the extract of jorum.
26. compositions as claimed in claim 4, wherein said nutritional preparation are selected from vitamin, antioxidant, natural herbal product and basic nutrition component.
27. compositions as claimed in claim 26, wherein said vitamin is selected from vitamin A, vitamin E, vitamin B
6, vitamin B
12, vitamin C and folic acid.
28. compositions as claimed in claim 26, wherein said antioxidant is selected from bata-carotene, silymarin and selenium.
29. compositions as claimed in claim 26, wherein said basic nutrition component is selected from methionine, leucine, lysine, valine, isoleucine, zinc, calcium, glucose, potassium, copper and ferrum.
30. compositions as claimed in claim 1, wherein said compositions is outer by oral, intestinal, the administration of intranasal, the suction that comprises spray, rectum, vagina and transdermal.
31. compositions as claimed in claim 4, the dosage range of wherein said antibiotics are 10-55mg/kg.
32. compositions as claimed in claim 4, the dosage range of wherein said antifungal are 50-80mg/kg.
33. compositions as claimed in claim 4, wherein the dosage range of used anticarcinogen is 5-30mg/kg.
34. compositions as claimed in claim 4, the dosage range of wherein said cardiovascalar agent are 0.5-10mg/kg.
35. compositions as claimed in claim 4, the dosage range of wherein said antiviral agent are 10-50mg/kg.
36. compositions as claimed in claim 4, the dosage range of wherein said CNS medicine are 0.1-0.5mg/kg.
37. compositions as claimed in claim 4, the dosage range 2-10mg/kg of wherein said anti-inflammatory/arthritis medicament.
38. compositions as claimed in claim 4, the dosage range of wherein said anti-TB/ leprosy medicament is 10-75mg/kg.
39. compositions as claimed in claim 4, the heavy scope of the agent of wherein said antihistamine/breathing medicament is 0.5-30mg/kg.
40. compositions as claimed in claim 4, the dosage range of wherein said corticosteroid are 0.05-5mg/kg.
41. compositions as claimed in claim 4, the dosage range of wherein said immunosuppressant are 5-15mg/kg.
42. compositions as claimed in claim 4, the dosage range of wherein said antiulcer agents be 2-45mg/kg.
43. compositions as claimed in claim 4, the dosage range of wherein said vitamin are 0.1-40mg/kg.
44. compositions as claimed in claim 4, the dosage range of wherein said antioxidant are 5-15mg/kg.
45. compositions as claimed in claim 4, wherein said basic nutrition dose of components scope is 20-55mg/kg.
46. compositions as claimed in claim 4, the dosage range of wherein said herb extracts are that 10mg/kg is to 1g/kg.
47. compositions as claimed in claim 4, the enhanced level of wherein said antibiotic bioavailability are 50-110%.
48. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said antifungal are 50-80%.
49. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said anticancer agent are 70-90%.
50. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said cardiovascalar agent are 60-100%.
51. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said antiviral agent are 70-95%.
52. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said CNS medicine are 90-95%.
53. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said anti-inflammatory medicament are 70-100%.
54. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said anti-TB/ leprosy medicament is 40-110%.
55. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said antihistamine medicament are 70-80%.
56. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said corticosteroid are 60-80%.
57. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said immunosuppressant are 80-100%.
58. compositions as claimed in claim 4, the enhanced level of the bioavailability of wherein said antiulcer agents are 60-80%.
59. Bioenhanced compositions, comprise Fructus cari carvi extract or its part or its mixture, the therapeutic agent of Rhizoma Zingiberis Recens extract and treatment effective dose, described therapeutic agent is selected from antibiotic, antibacterial, antifungal, antiviral agent, antitubercular agent, antileprotic, anti-inflammatory agent, anti-arthritic, cardiovascular drug, antihistaminic, respiratory distress abirritant, immunosuppressant, antiulcerative, dietetic product, herbal medicinal product and similar compositions.
60. test kit comprises the independent of one or more therapeutic agents and effective dose or the caraway water extract or the biologically-active moiety that make up with at least a other bio-enhancer arbitrarily.
61. Fructus cari carvi extract or part are as the purposes of bio-enhancer.
62. purposes as claimed in claim 61, wherein said Fructus cari carvi extract or part are used with at least a other bio-enhancer that is selected from piperine or Rhizoma Zingiberis Recens extract or its mixture.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IB2003/000293 WO2004067018A1 (en) | 2003-01-30 | 2003-01-30 | Bioavailability enhancing activity of carum carvi extracts and fractions thereof |
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| Publication Number | Publication Date |
|---|---|
| CN1738632A true CN1738632A (en) | 2006-02-22 |
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|---|---|
| EP (1) | EP1587521A1 (en) |
| JP (1) | JP2006514962A (en) |
| CN (1) | CN1738632A (en) |
| AU (1) | AU2003202112A1 (en) |
| WO (1) | WO2004067018A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526668A (en) * | 2011-03-02 | 2012-07-04 | 青岛大学 | Ginger/white pepper composition for relieving vomiting due to cancer chemotherapy and enhancing effect of cancer chemotherapy and preparation method thereof |
| CN102757865A (en) * | 2011-04-25 | 2012-10-31 | 湖北中烟工业有限责任公司 | Carum carvi and dried ginger composite extract and purpose thereof as tobacco product additive |
| CN108205032A (en) * | 2017-12-29 | 2018-06-26 | 佛山市南海东方澳龙制药有限公司 | The detection method of ketoconazole ingredient liquid content in a kind of compound ketoconazole ointment |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080181947A1 (en) | 2006-09-26 | 2008-07-31 | Astellas Pharma Inc. | Controlled release dosage form of tacrolimus |
| WO2008084698A1 (en) | 2006-12-28 | 2008-07-17 | Astellas Pharma Inc. | Tacrolimus sustained release pharmaceutical composition |
| FR2979826B1 (en) * | 2011-09-08 | 2013-12-27 | Univ Bordeaux Segalen | ANTI-INFLAMMATORY COMPOSITION |
| JP7085998B2 (en) | 2016-02-12 | 2022-06-17 | シプラ・リミテッド | Pharmaceutical composition comprising an antiretroviral drug and a pharmacokinetic enhancer |
| IT201600075072A1 (en) * | 2016-07-18 | 2018-01-18 | Nathura S P A | Pharmaceutical or dietary supplement composition for the treatment of intestinal constipation |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3511862A1 (en) * | 1985-04-01 | 1986-10-09 | Klinge Co Chem Pharm Fab | Pharmaceutical composition |
| WO1991012792A1 (en) * | 1990-03-02 | 1991-09-05 | The Partnership Of Isaac G. Eliaz And Shmuel Gonen | Method and product for promoting hair growth and treating skin conditions |
| JPH06510046A (en) * | 1991-08-26 | 1994-11-10 | アボツト・ラボラトリーズ | Compositions and methods for sublingual or buccal administration of therapeutic agents |
| JP2946452B2 (en) * | 1994-11-04 | 1999-09-06 | カディラ ラボラトリーズ リミテッド | Composition containing piperine |
| US5744161A (en) * | 1995-02-24 | 1998-04-28 | Sabinsa Corporation | Use of piperine as a bioavailability enhancer |
| EP0831870A4 (en) * | 1995-06-07 | 1998-09-16 | Avmax Inc | Use of essential oils to increase bioavailability of oral pharmaceutical compounds |
| CH688787A5 (en) * | 1995-09-05 | 1998-03-31 | Dieter Linsig | Synergistic mixture of essential oils or essences |
| IN186315B (en) * | 1996-12-12 | 2001-08-04 | Panacea Biotec Ltd | |
| DE10022801A1 (en) * | 2000-05-10 | 2001-11-15 | Ernestina C Loeckinger | Well tolerated natural medicament for treating urological, gynecological or intestinal diseases, comprising black caraway oil, tea tree oil and grapefruit seed extract. |
| DE10196213T1 (en) * | 2000-05-19 | 2003-04-30 | Sabinsa Corp | Process of increased bioavailability of nutrients and pharmaceutical preparations with tetrahydropiperine and analogues and derivatives thereof |
| JP2002138045A (en) * | 2000-10-30 | 2002-05-14 | Ichimaru Pharcos Co Ltd | Inhibitor for inhibiting differentiation induction of pre- adipocyte |
| JP2003095915A (en) * | 2001-09-25 | 2003-04-03 | Shiseido Co Ltd | Skin care composition |
-
2003
- 2003-01-30 WO PCT/IB2003/000293 patent/WO2004067018A1/en active Application Filing
- 2003-01-30 EP EP03700970A patent/EP1587521A1/en not_active Withdrawn
- 2003-01-30 JP JP2004567372A patent/JP2006514962A/en active Pending
- 2003-01-30 AU AU2003202112A patent/AU2003202112A1/en not_active Abandoned
- 2003-01-30 CN CNA038259028A patent/CN1738632A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526668A (en) * | 2011-03-02 | 2012-07-04 | 青岛大学 | Ginger/white pepper composition for relieving vomiting due to cancer chemotherapy and enhancing effect of cancer chemotherapy and preparation method thereof |
| CN102526668B (en) * | 2011-03-02 | 2013-10-09 | 青岛大学 | Ginger/white pepper composition for relieving vomiting due to cancer chemotherapy and enhancing effect of cancer chemotherapy and preparation method thereof |
| CN102757865A (en) * | 2011-04-25 | 2012-10-31 | 湖北中烟工业有限责任公司 | Carum carvi and dried ginger composite extract and purpose thereof as tobacco product additive |
| CN102757865B (en) * | 2011-04-25 | 2013-06-05 | 湖北中烟工业有限责任公司 | Carum carvi and dried ginger composite extract and purpose thereof as tobacco product additive |
| CN108205032A (en) * | 2017-12-29 | 2018-06-26 | 佛山市南海东方澳龙制药有限公司 | The detection method of ketoconazole ingredient liquid content in a kind of compound ketoconazole ointment |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1587521A1 (en) | 2005-10-26 |
| WO2004067018A1 (en) | 2004-08-12 |
| WO2004067018A8 (en) | 2006-02-23 |
| JP2006514962A (en) | 2006-05-18 |
| AU2003202112A8 (en) | 2004-08-23 |
| AU2003202112A1 (en) | 2004-08-23 |
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