it is one of the most prized culinary herb which is used extensively in india . the herb finds very frequent mention in ayurved and other indian systems of medicine prescriptions used against a wide variety of ailments . it remained a scientific curiosity that a single plant can have biological activities for such a large variety of ailments or diseases for which these prescriptions are employed . [ 0011 ] carum carvi linn seeds are known as jira ( beng . ), shahjiru ( guj . ), kala jira , shiajira ( hindi ), shalajira ( mar .) carum carvi is an annual or biennial glabrous herb , 30 - 100 cm in height , native to europe and west asia , found growing wild in himachal pradesh and cultivated in the hills and plains of north india and in the hills of south india for its aromatic seeds . its seeds are widely used as a spice for culinary purposes and for flavouring bread , biscuits , cakes , candies , cheese , curries , pickles , sausages , meat products , confectionery and liqueurs of kummel type . they are also used as a flavouring constituent in cordials and in certain preparations of cannabis . in medicine , they are used as carminative , mild stomachic , aromatic and diuretic . both the seeds and the essential oils ( caraway oil ) are prescribed in flatulent colic and stomach derangements . in patients suffering from lumbago and rheumatism , exposing the affected parts to the vapours from the seeds gives relief from the disease . the alcoholic extract of the fruits show dose - dependent antispasmodic effect . its water finds use as a vehicle for paediatric medicines . hexane extract of the fruits was found to have excellent larvicidal activity against the mosquito culex pipiens fatigans wiedm . [ marketing of minor spices in india , 1968 , 119 ; 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 ]. the dried crushed seeds , on steam distillation , gave a pale yellow to light brown essential oil ( known as caraway oil ) with a strong aromatic odour . the oil content of the seeds varies according to the degree of maturity of the seeds . storage affects the oil content of seeds up to 2 . 8 per cent per annum . all indian samples of the seeds contained 5 . 8 - 8 . 1 per cent of caraway oil . carvone and the limonene are the chief constituents of the oils and its odour and flavour are mainly attributed to them . other constituents present in the oil are α - and β - pinene and ρ - cymene . besides the above constituents , camphene , δ 3 - carene , dihydrocarvone , β - fenchene , myrcene , α - and β - phellandrene , sabinene , α and γ - terpinene , α - thujene , terpinolene , tricyclene , d - and 1 - dihydropinol , 1 - neodihydrocarveol , 1 - isodihydrocarveol , carveol , d - dihydrocarveol , acetaldehyde , methyl alcohol , furfural have also been isolated from european caraway oil ( arctander , 124 ; dijkstra and 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 ). caraway oil is primarily used like caraway seeds in flavouring several food products , and in medicine as carminative . it is the main ingredient in the scandinavian “ snaps ” and the german “ kummel ”. it is employed in gargle preparations , toothpaste flavours , chewing gum , candy and as a masking agent in bad tasting pharmaceutical preparations and obnoxius insecticides . it also exhibits neurotropic anti - spasmodic activity . in mixture with alcohol and castor oil , it is used for the treatment of scabies . the essential oil shows moderate anti - bacterial and anti - fungal property against several bacteria and fungi . decarvonised oil is sold in the market for scenting cheap soaps , in jasmine bases and tabac perfumes ( ipc ., 54 ; arctander , 125 ; chopra et al , 1958 , 92 ; chem abstr , 1968 , 68 , 48218 ; narayan et al indian drugs , 1979 - 80 , 17 , 394 ; el - keltawi et al , herba pol , 1980 , 26 , 245 ). the seeds also contain 3 - glucosides and 3 - galactosides of kaempferol , quercetin and isorhamnetin , and a hydrocarbon ( m p , 62 - 63 °). presence of 5 - methoxy -, and 8 - methoxy psoralens , sterol , umbelligerone , scopoletin and herniarin is also reported . the fatty acid composition of the oil is : palmitic , 3 . 6 ; oleic , 60 . 7 ; linoleic , 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 ). the aqueous , aqueous — alcoholic , ketonic , ethereal , halogenated solvents extracts of the plant parts were evaluated with different therapeutic categories of drugs and nutraceutical ( vital amino acids , metals , antioxidants , vitamins ) and herbal drugs . the bioavailability / bioefficacy enhancing ( be ) activity of carum carvi extracts was found to be consistent from 5 mg to 100 mg irrespective of the amount of the drug ( s ) present in the formulation . sub - fractions of the active extracts were also evaluated , with the same categories of drugs . the doses of the fraction ( s ) responsible for the be activity ranged from 1 . 0 to 55 mg . the parent extract as well as the active fraction ( s ) were found to be active individually as well as in combination with each other with different categories of drugs . the individual extract or its fractions were found to be 20 - 110 % more active when used in combination with bioenhancer products developed from zingiber officinale . the effective range for zingiber officinale . bes was 10 - 150 mg . besides both the parent extracts as well as their fractions from carum carvi in different combinations showed pronounced activity ranging from 25 - 95 % in presence of piperine . the amount of piperine in these formulations ranged from 3 - 15 mg . the extracts or its fractions either in presence or absence of bes from zingiber officinale . and / or piperine have been found to be highly selective in their bioavailability and / or bioefficacy enhancing activity . this is apparent from the degree of bioavailibility and / or bioefficacy enhancement caused by these extracts / fractions as exmeplified in accompanying examples . the reasons for this selective pattern may be attributable to one or more than one of the following reasons : ( a ) promoting the absorption of drugs from git , ( b ) inhibiting or reducing the rate of biotransformation of drugs in the liver or intestines , ( c ) modifying the immune system in a way that the overall requirement of the drug is reduced substantially , ( d ) increasing the penetration or the entry into the pathogens even where they become persistors within the macrophages such as for mycobacterium tuberculosis and such others . this eventually ensures the enhanced killing of these organisms well secured within the places otherwise inaccessible to the active drug , ( e ) inhibiting the capability of pathogens or abnormal tissue to reject the drug e . g ., efflux mechanisms frequently encountered with anti - malarial , anti - cancer and anti - microbial drugs , ( f ) modifying the signalling process between host and pathogen ensuring increased accessibility of the drugs to the pathogens , ( g ) enhancing the binding of the drug with the receptors like proteins , dna , rna , etc ., in the pathogen , thus potentiating and prolonging its effect leading to enhanced antibiotic activity against pathogens , ( h ) besides above plausible modes of action , the bioenhancer agents may also be useful for promoting the transport of nutrients and the drugs across the blood brain barrier , which could be of immense help in the control of diseases like cerebral infections , epilepsy and other cns problems . primarily , but not exclusively , the invention enhances the carrier mediated entry of drugs and also the passive diffusion and the active transport pathways in the tissue which are responsible for transporting physiological substances such as nutraceuticals to their target sites . as applicable to any mechanism of action the products of this invention contribute in a synergistic and / or additive manner so that most drugs and nutraceuticals in presence of the products described in the present art are more bioavailable or bioefficaceous as a result of one or more of these mechanisms . the bioavailability and / or bioefficacy of drugs and nutraceuticals is also relevent to animal health besides being important for humans . the invention therefore is also intended to be used in veterinary preparations . the following examples are intended to demonstrate some of the preferred embodiments and in no way should be construed so as to limit the scope of the invention . any person skilled in the art can design more formulations , which may be considered as part of the present invention . example 1 preparation of colourless , non - pungent piperine by a novel process as already claimed ( indian patent no 1726890 ) example 2 . preparation of fully characterized bes from zingiber officinale as already claimed in a copending patent . example 3 . list of drugs cited below as some of the examples for the purpose of the present invention . categories drugs i . antibiotics fluoroquinolones : cipro -, nor -, p -, and o - floxacins macrolides : erythro -, roxythro -, and azithromycin cephalosporins : cefixime , cefalexin , cefadroxil and cefatrioxone , cefidinir penicillins : amoxycillin cloxacillin aminoglycosides : amikacin , kanamycin ii . antifungal fluconazole , amphotericin b , ketoconazole iii . anti - viral acyclovir , zidovudine iv . anti - cancer methotrexate , 5 - fluorouracil , dauxorubicin , cisplatin , adriamycin v . cvs drugs amlodipine , lisinopril , atenolol vi . cns drugs alprazolam haloperidol vii . anti - inflammatory diclofenac , piroxicam , nimesulide , rofecoxib antiarthritic viii . anti - tb / antileproxy rifampicin , isoniazid , pyrazinamide , ethambutol , dapsone drugs ix . anti histamines / salbutamol , theophylline , bromhexine , loretidine respiratory disorders x . carticosteroids prednisolone , dexamethsone , betamethasone xi . immunosuppressants cyclosporins , tacrolimus , mycophenolate mofetil xii . anti - ulcer ranitidine , cimetidine , omeprazole % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale ciprofloxacin 78 55 110 68 133 p - floxacin nil 61 70 53 75 o - floxacin 65 52 167 49 170 norfloxacin 55 nil 65 nil 60 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale erythromycin 70 95 100 68 105 roxythromycin 65 110 95 72 98 azithromycin 55 89 90 78 86 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale cefalexin nil 90 90 75 79 cefadroxil 67 70 95 68 85 cefatrioxone 72 nil 78 nil 75 cefixime 80 nil 79 nil 82 cefidinir 89 60 95 35 130 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale amoxycillin 75 120 115 80 100 cloxacillin 110 87 95 76 110 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale amikacin 85 nil 100 nil 92 kanamycin nil 72 87 65 68 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale fluconazole 65 87 98 120 110 amphotericin 78 nil 90 nil 80 b ketoconazole 55 105 100 125 96 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale methotrexate 76 65 89 87 102 5 - fluorouracil 90 87 110 110 100 dauxorubicin nil 68 70 72 69 cisplatin nil nil nil 56 55 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale amlodipine nil 43 50 68 65 lisinopril 79 85 95 76 90 atenolol 100 nil 93 nil 97 propranolol 68 84 90 76 75 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale acyclovir 78 96 100 82 90 zidovudine 92 140 95 105 87 % enhancement in bioavailability be from carun be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale alprazolam nil 65 70 76 80 haloperidol 95 nil 90 nil 85 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale diclofenac nil 120 100 90 95 piroxicam nil 110 98 86 76 nimesulide 100 132 140 144 145 rofecoxib 75 nil 70 nil 80 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale rifampicin 110 45 170 65 140 isoniazid nil nil nil nil nil pyrazinamide 45 nil 50 nil 55 ethambutol nil nil nil nil nil dapsone 56 34 67 46 68 ethionamide 68 45 65 56 70 cycloserine 70 67 80 71 75 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale salbutamol 75 60 89 78 80 theophylline 70 65 79 76 89 bromhexine nil 67 70 67 71 loratidine 76 nil 70 nil 80 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale prednisolone 65 nil 67 nil 60 dexamethasone 72 66 77 76 73 betamethasone 80 72 89 75 77 % enhancement in bioavaiiability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale cyclosporin a 100 nil 105 116 120 tacrolimus 90 105 95 75 114 mycophenolate nil nil nil nil nil mofeit % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale ranitidine 67 21 70 147 150 cimetidine 72 nil 84 98 100 omeprazole 76 nil 70 nil 75 % enhancement in bioavailability be from carum be from carum carvi carum piperine carvi + zingiber + zingiber carvi as be piperine officinale officinale echinacea nil 75 76 66 65 augustifolia tinospora 76 85 90 67 71 cordifolia picrorrhiza 80 78 110 56 76 kurroa aegles 65 nil 65 nil 60 marmelos andrographis 68 63 72 55 54 paniculata emblica ribes nil nil nil 65 68 asparagus nil 58 55 44 45 racemosus terminalia 92 nil 87 nil 91 chebula withania 76 55 70 64 76 somnifera centella 68 nil 65 nil 62 asiatica category i . vitamins vitamin a vitamin e vit . b1 vit . b6 vit . b12 vit . c folic acid ii . antioxidants β - carotene silymarin selenium iii . natural herbal products curcumin boswellic acid rutin piperine iv . essential nutritional components methionine lysine leucine valine isolencine zinc calcium glucose potassium copper iron
the invention relates to the isolation of an extract and / or its fraction from the plant carum carvi , its standardization with its intended use as drug bioavailability and / or bioefficacy enhancer for the drugs belonging to therapeutic categories such as but not limited to antimicrobial , antifungal , anti - viral , antitubercular , antileprosy , antiinflammatory / anti - arthritic , cardiovascular , antihistaminics , respiratory distress relieving drugs , immunosuppressants , anti - ulcers , nutraceuticals in compositions to be administered orally / parenterally , topically , inhalations , rectally , vaginally in human beings and / or veterinary conditions .