CN1311674A

CN1311674A - Antioxidant, antiproliferous compositions, comprising a carnitine and a cerotenoid

Info

Publication number: CN1311674A
Application number: CN99809268A
Authority: CN
Inventors: C·卡瓦扎
Original assignee: Sigma Tau HealthScience SpA
Current assignee: Sigma Tau HealthScience SpA
Priority date: 1998-08-03
Filing date: 1999-07-29
Publication date: 2001-09-05
Also published as: EP1102584A2; IL140797A0; EE200100052A; HUP0102807A2; KR20010072146A; NO20010532D0; WO2000007581A3; NO20010532L; IT1302125B1; MA26666A1; AR021172A1; WO2000007581A2; IS5816A; SK1252001A3; ITRM980516A0; JP2002522382A; ITRM980516A1; BR9912703A; TNSN99152A1; HK1039062A1

Abstract

A composition is disclosed which comprises as characterizing active ingredients propionyl L-carnitine and at least one carotenoid, typically the lycopene extracted from tomato for the prevention and/or therapeutic treatment of various alterations and pathological states induced by free radicals and by lipoperoxidation phenomena.

Description

The antioxidant, the antiproliferative compositions that contain carnitine and carotenoid

The fat peroxidating phenomenon that the present invention relates to can be used for preventing and/or treating by environmental pollution and atherosclerosis, blood vessel, heart or brain causes free radical to have the disease that is produced; Comprise the hyperblastosis of prostate, uterus, breast or colon; Comprise vision and amphiblestroid compositions that cataract and amphiblestroid speckle are degenerated.

Therefore, desire the supply or preventive effect or the strict therapeutical effect that play according to compositions on one's body at the particular individual that uses, compositions can be taked the form of food fill-in or medicine and play the effect of food fill-in or medicine.

More specifically, the present invention relates to can oral administration, non-intestinal, rectum, skin is saturating or eye instils and carries out administration compositions, and it comprises following combination:

(a) propiono L-carnitine or its pharmaceutical salts, can make up with other " carnitine ", " carnitine " here is meant the L-carnitine or is selected from acetyl group L-carnitine, the alkanoyl L-carnitine of valeryl L-carnitine and isovaleryl L-carnitine or their pharmaceutical salts; And

(b) carotenoid preferably is selected from lycopene, alpha-carotene, beta-carotene, cryptoxanthin, kryptoxanthin, lutein or their mixture or contain the extract of the crude vegetable product of carotenoid are typically Fructus Lycopersici esculenti extract (Lycopersiconesculentum).

Carotenoid is one group of long-chain plant pigment that contain up to 40 carbon atoms, has two key conjugated systems, tool terpenes character (tetraterpene).Carotenoid is present in senior plant, chloroplast and is positioned in those plastids that lack chlorophyllous plant zone (carotenoid wherein increased to some extent in the period of maturation for some root and many flowers and fruit, Fructus Lycopersici esculenti for example); Also in bluegreen algae, some photosynthetic bacterium and some fungus, found carotenoid.In light compositing, carotenoid has been played the part of a chlorophyllous additional role, and it absorbs some light and gives chlorophyll itself with energy conduction.

Although in plant world, there is more than 600 kind of carotenoid, only there are 40 kinds in the human diet, can only there be 14 kinds by what internal organs absorbed, remaining is made of non-absorbent epoxide.Prevailing in these 14 kinds is lycopene, alpha-carotene, beta-carotene, lutein, cryptoxanthin and beta-cryptoxanthin.

There are the two keys of 11 (individual) linear conjugate (there are 9 in beta-carotene wherein) in lycopene, and is the carotenoid that has long-chain in the two keys of linear conjugate.

People carried out requirement to this ad hoc structure and its as the relation between the big ability of antioxidant.

Although there is metabolic interaction between lycopene and beta-carotene, lycopene can't be converted into beta-carotene with himself in vivo, and the latter is a feature with the trimethyl-cyclohexane basic ring on the carbochain both sides.

On the other hand, beta-carotene can will itself be converted into trans retinol and tretinoin by the chain reduction, and has the effect of provitamin A sample.

These chemical compounds have substantial oxidation resistance, but wherein lycopene has maximum blocking ability to singlet oxygen, and its twice that act as for example beta-carotene effect is many.

Lycopene can be absorbed by the body, and particularly in the presence of fat, and can find in blood and fat that it exists with two kinds of forms, cis-and trans-lycopene.

As all carotenoid, lycopene can not lean on health synthetic, must absorb by diet.

Have many foods to contain carotenoid, comprise Fructus Caricae, powder grapefruit, Herba Spinaciae, Fructus Pruni, milk and egg, but they contain the lycopene of maximum all than Fructus Lycopersici esculenti only in the Fructus Lycopersici esculenti.

Except its substantial oxidation resistance; people are interested in also because the result of some epidemic research the lycopene; these results show the carotenoid that has the effect of provitamin A sample; for example beta-carotene itself can play a protective role to the tumor of some form, and does not need to be converted into the form of retinol.Some expections and retrospective the survey showed that exists inverse correlation to concern between the carotene of the vegetable of being rich in carotene and fruit consumption or high plasma concentration and tumor risk (especially lung tumors).These results are all owing to carotenoid, only because it is the precursor of vitamin A.Yet nearest clinical experiment shows again, compares with a large amount of crowds that lack this vitamin in the diet, uses beta-carotene that the risk of tumor is not had beneficial effect in diet separately.

In smoker group or have in the group of individuals of suffering from asbestosis danger and also obtained same negative findings.After these data are handled, find that again the carotenoid except beta-carotene is contributed to some extent for obtaining to test detectable protective effect with other.

Can characterization the basis describing lycopene and make the people believe that it can play the beneficial organism effect in vivo, ground be that it has strong antioxidation, it should be noted that most the effect of anti-singlet oxygen, the latter is one of active oxygen product of tool in the free radical production process.Except the effect of its anti-singlet oxygen, lycopene has activity when protection cell and tissue are avoided the damage of other reactive specy oxygen (for example hydrogen peroxide and nitrous oxide).

The partly cause that the lycopene of taking in diet can play useful health promotion effect is that these of lycopene are specifically active, and these sp acts make it be in prominent position among all other natural inhibitors just.

In fact have now found that, compare that the blood concentration of suffering from shown beta-carotene, the particularly lycopene that goes out of the crowd of the higher potential danger of the blood concentration of the patient of myocardial infarction and those cholesterol or triglyceride is very low with matched group.The relevant this viewpoint with the lipotropism peroxidation of lycopene of above-mentioned phenomenon also can display from proving that lycopene be present in the research that also can prevent its oxidation the LDLs.

Confirm that now when measuring in cell culture (C3H/10T1/2 cell), the lipotropism peroxidation of lycopene also is better than β-and alpha-carotene, lycopene can prevent that their tumor from forming and transforms in cell culture.The lipotropism peroxidation of lycopene has also been explained the ability that it prevents the damage of atherosclerosis and atherosclerotic blood vessel, also suppress simultaneously with its immunoglobulin and bonded cell in exchange enhanced activity and tumor cell proliferation relevant.

The spontaneous development of breast tumor and leukaemia (H1-60 promyelocyte leukaemia system) and rat glioma C-6 cells in vitro are grown or are formed conversion aspect by the inductive tumor of chemicals in suppressing the rat body, and lycopene is the strongest effective carotenoid.

The sick research of epidemiology has proved and has had the inverse correlation relation that between the risk of lycopene of taking in diet and developing tumor of prostate therefore lycopene can be used as a kind of preventive means in this special disease.The risk of mammary gland and lung tumors also has same situation.

Lycopene, another disease that can produce protective effect as lutein, cryptoxanthin is the patches of macula degeneration (AMD) relevant with the age.

People know the key player of L-carnitine and alkyl acyl derivative thereof, and they can play a role on metaboilic level, especially for Oxidation and the fatty acid utilization by beta oxidation.

In fact, no matter be from diet, absorb or all in organ, concentrated by the synthetic L-carnitine that obtains of health by blood, very active aspect the metabolism that they utilize at fatty acid, for example in skeletal muscle and heart.

The L-carnitine lacks can cause myopathy, and oral L-carnitine can improve the clinical condition of this class myopathy.In the mitochondrion oxidation of glucose, the L-carnitine is playing an important role aspect the generation of energy too, and consequently the normal energy metabolism on cardiac muscle and muscle level needs the L-carnitine of enough levels.

The giving of L-carnitine can be improved the clinical symptoms of Coronary Insufficiency patient to tolerance, coronary blood flow itself and the cardiac decompensation of anxiety.

Other biological property that L-carnitine and derivant thereof, especially propiono are foretold carnitine is that it has the ability of stabilizing cell membrane and can protect cell to avoid because the damage that oxidizing process causes.

Surprisingly, the compositions that contains the combination of following characteristic that has now found that: (a) propiono L-carnitine or its pharmaceutical salts, and (b) be selected from lycopene, and alpha-carotene, beta-carotene, cryptoxanthin, kryptoxanthin,

The carotenoid of lutein or their mixture.Prevent and/or treat aspect the following disease extremely effective: the fat peroxidating phenomenon by environmental pollution and atherosclerosis, blood vessel, heart or brain causes free radical to have the disease that is produced; The proliferative disorder of tissue comprises prostate, uterus, breast or colon; Comprise vision and retina imbalance that cataract and amphiblestroid speckle are degenerated, this is because these components have strong synergism.

Now also find component (a) can also be further preferably bag be selected from following " carnitine ": the L-carnitine; acetyl group L-carnitine; valeryl L-carnitine and isovaleryl L-carnitine or their medicinal salts or they mixture; and component (b) can be made up of the plant product extract that contains it; Fructus Lycopersici esculenti (Lycopersicon esculentum, Solanaceae family) extract for example.

(a): weight ratio (b) is 1: 0.1 to 1: 10.

Toxicological experiment

No matter be that the carnitine or the toxicity of its derivant and lycopene and other carotenoid (for example corpus luteum matter, cryptoxanthin, kryptoxanthin and beta-carotene) are all lower, and animal has toleration preferably to it, especially when oral administration.

By implementing the L-carnitine (1g/Kg) of orally give rat high dose; or propiono L-carnitine (1g/Kg); or L-carnitine (250mg/Kg) adds propiono L-carnitine (250mg/Kg) and adds acetyl group L-carnitine (250mg/Kg) and add isovaleryl L-carnitine (250mg/Kg) and can confirm above-mentioned advantage, also can confirm above-mentioned advantage by giving the natural tomato extract that 50mg/Kg lycopene or 1g/Kg contain 5% lycopene.

The compositions of orally give rat 1g/Kg propiono L-carnitine and 50mg/Kg lycopene can prove that also it has toleration preferably, and does not cause the death of accepting to handle animal.

Give the carnitine mixture (L-carnitine 250mg/Kg add acetyl group L-carnitine 250mg/Kg add propiono L-carnitine 250mg/Kg add isovaleryl L-carnitine 250mg/Kg) and the compositions of 50mg/Kg lycopene and also obtained same result.

(30 days) orally give rat every day propiono L-carnitines (500mg/Kg) in one long period, or the compositions of the mixture of various carnitines (L-carnitine 150mg/Kg add acetyl group L-carnitine 150mg/Kg add propiono L-carnitine 150mg/Kg add isovaleryl L-carnitine 150mg/Kg) and 25mg/Kg lycopene has also obtained same ideal results.

When finishing in 30 days, dead and poisoning indication do not appear in the rat of accepting to handle.Physical and chemical experiment is found, accepts red blood cell count(RBC) and the numeration of leukocyte of processing animal and all acts normally, and finishes the back as processing major organs is carried out the result that histological examination obtains.

Experiment with the isolated liver cell of carbon tetrachloride intoxicating

Active in order to estimate the present composition to the antioxidation of free radical and protection, they are analyzed for the effect with the isolated liver cell culture of carbon tetrachloride intoxicating.

Known carbon tetrachloride (CCl ₄) can the inducing cell film the fat peroxidation, it can cause necrocytosis.

These that carry out in the rat hepatocytes culture experimental results show that with free radical and discharge relevant CCl ₄Fat peroxidating and toxic action can reduce because of there being the carnitine mixture in the culture; above-mentioned carnitine mixture is by the L-carnitine; acetyl group L-carnitine; propiono L-carnitine and isovaleryl L-carnitine are formed; weight ratio between them is 1: 1, and peroxidating and toxic action also can reduce because of there being propiono L-carnitine (100mg/L) (especially when being used in combination with lycopene (20mg/L) or the Fructus Lycopersici esculenti extract that contains 5% lycopene) in the culture.

In order to carry out these experiments, utilize the described method of Seglen (Seglen F.O.Meth.Cell.Biol.Chem., 264,4747), isolate hepatocyte from the liver of rat.

By to being in the analysis of alanine aminotransferase in the cell culture supernatant liquid (AlaAT) and aspartate aminotransferase (aspaAT), can measure and obtain CCl ₄The damage of inductive cell membrane and carnitine mixture or propiono L-carnitine or lycopene and their protective effect that compositions played (Beckman 700-Encore 2 automatic biochemical analytical systems).

Adopt barbiturates method (Ohkawa H.Anal.Biochem., 95,351,1979) to The compounds of this invention for CCl ₄, malonyl aldehyde the snperoxiaized protective effect of fat estimate.

Processing is fixed in hepatocyte in formalin or the glutaraldehyde after finishing under optics and ultramicroscope, its cytology is measured.These experimental results show, resist membrane damage and opposing CCl the protection hepatocyte ₄Inductive fat peroxidating aspect exists beat all synergism between carnitine mixture and the lycopene and between propiono L-carnitine and the lycopene.

The synergism that exists between carnitine, especially propiono L-carnitine and the lycopene in to the mensuration of malonyl aldehyde (index of a fat peroxidation) also clearly.

Hepatocellular cytology measures confirmation: non-viable non-apoptotic cell decreases after handling with propiono L-carnitine and lycopene, yet, in superstructure is measured, as matched group (CCl ₄) in cell show that hematochrome is unusual, nuclear membrane is irregular, the mitochondrial crista in the mitochondrion disappears and ribosome quantity when reducing, those not only are exposed to CCl ₄And the cell that is exposed to carnitine and lycopene unexpectedly presents int cell membrane and nuclear, the heterochromosome of rule and the hematochrome and the ribosome quantity of rule.

The normalization that is exposed to the hepatocellular cytology's outward appearance in carnitine mixture and the lycopene combined activity is remarkable astoundingly; and the effect of individualized compound (inadequacy) is not remarkable, and therefore there is significant synergism in proof between carnitine and lycopene.

Table 1

Be suspended in the concentration (AlaAT nmol/min) of the alanine aminotransferase in the liver cell culture liquid, above-mentioned liver cell culture liquid is exposed to (C=carnitine mixture under carbon tetrachloride (contrast) and independent carnitine mixture or propiono L-carnitine or natural tomato carotenoid extract or lycopene or their the various compositionss; P=propiono L-carnitine; TE=natural tomato extract; The L=lycopene).

Time (hour) 48 16

Contrast 24.6 ± 2.1 26.8 ± 2.3 30.5 ± 4.5

C 20.6±3.2 21.9±3.3 26.4±2.8

P 19.4±2.1 22.3±3.1 25.7±3.7

TE 22.3±1.8 24.3±2.7 24.7±2.9

L 22.1±2.1 20.6±2.4 23.6±2.1

C+TE 11.9±1.9 8.6±1.1 5.1±1.7

C+L 12.2±1.8 10.5±1.5 5.4±1.9

P+L 11.5±2.1 9.9±2.4 6.2±1.5

Table 2

Be suspended in the concentration (AspaAT nmol/min) of the aspartate aminotransferase in the liver cell culture liquid, above-mentioned liver cell culture liquid is exposed to (C=carnitine mixture under carbon tetrachloride (contrast) and independent carnitine mixture or propiono L-carnitine or natural tomato carotenoid extract or lycopene or their the various compositionss; P=propiono L-carnitine; TE=natural tomato extract; The L=lycopene).

Time (hour) 48 16

Contrast 8.5 ± 0.6 10.9 ± 1.1 12.1 ± 1.5

C 8.1±0.9 9.9±0.8 9.8±1.1

P 8.9±0.9 9.2±1.2 9.1±1.7

TE 8.2±0.8 9.1±0.9 9.0±1.2

L 8.8±1.8 8.9±0.9 9.0±1.2

C+TE 5.4±0.7 3.2±0.9 3.0±0.5

C+L 5.6±1.1 3.1±0.8 3.5±1.2

P+L 5.5±0.9 3.5±1.2 3.2±0.8

Test inductive cataract experiment

In the factor relevant with the eye cataract, based on their pathogenic importance and to the functional disorder of retina blood supply, not only reference has been made in the glucose metabolism damage, and free radical and lipid fat peroxidation also made reference, so we are with Gabbay (Gabbay K.H., N.Engl.J.Med., 288,831,1973) the described method that is rich in the galactose diet has been induced the cataractous generation of eye rat on one's body experimentally.

After handling in 8 days, having obtained the crystalline lens opacification on one's body rat, according to the described method of Sippel (SippelT.O., Invest.Ophthamol., 5,568,1966), is I, II and III level with regard to its order of severity with the series classification that increases progressively.These results that obtained prove; it is (oral to give the carnitine mixture together with galactose; 400mg/Kg; the L-carnitine; acetyl group L-carnitine; the compositions of propiono L-carnitine and isovaleryl L-carnitine, their dosages each other are consistent according to the weight) or propiono L-carnitine (400mg/Kg) or lycopene (5mg/Kg) or contain the natural tomato extract (100mg/Kg) of 5% lycopene or the order of severity that these product combination things can reduce the ophthalmic injuries that is caused by galactose.But during 8 days galactose are handled, test simultaneously and handle rat carnitine mixture and the compositions of lycopene or the compositions of propiono L-carnitine and lycopene, almost can suppress the generation of crystalline lens opacification fully.

Table 3

In the rat body of galactosemia, separately or with various carnitine mixture, propiono L carnitine, natural tomato carotenoid extract and the lycopenes of being used in combination (20 rats are one group) tested in the inhibition of crystalline lens opacification.

Handle the opacification degree of lens

Mg/kg (the crystalline lens number of being tested)

Ⅰ Ⅱ Ⅲ

Contrast 0 10 10

Carnitine mixture (400mg/kg) 0 15 5

Propiono L carnitine (400mg/kg) 0 12 8

Natural tomato carotenoid extract (100mg/kg) 884

Lycopene (5mg/kg) 64 10

Carnitine mixture (400mg/kg)+

Natural tomato carotenoid extract (100mg/kg) 12 80

Carnitine mixture (400mg/kg)+lycopene (5mg/kg) 12 62

Propiono L carnitine (400mg/kg)+

Natural tomato carotenoid extract (100mg/kg) 14 60

Propiono L carnitine (400mg/kg)+lycopene (5mg/kg) 15 60

The intravital experimental atherosclerosis experiment of rabbit

In these experiments, in the rabbit body, estimating separately or with the various carnitine mixture that are used in combination, propiono L carnitine, lycopene and the natural tomato extract that contains 5% lycopene with testing inductive atherosclerotic effect.

The New Zealand rabbit that to adopt one group of average weight be 2.9kg carries out this experiment, in successive 30 days, adds the cholesterol of 0.5% (weight ratio) in its standard diet.Same animal accepts to be rich in the diet of cholesterol every day; dosage should be 400mg/Kg carnitine mixture (L-carnitine mutually; acetyl group L-carnitine; the compositions of valeryl L-carnitine and isovaleryl L-carnitine; it is consistent that their dosages each other calculate by body weight), or be 400mg/Kg propiono L-carnitine, or be the 5mg/Kg lycopene; or for 100mg/Kg contains the natural tomato extract of 5% lycopene, or the various combinations of same product.When processing in 30 days finished, the center tremulous pulse extraction blood sample from each animal ear carried out lipoprotein analysis (Hatch F.T.Adv.Lipid Res., 6,1,1968) according to the method that Hatch provides.

Put to death animal, therefrom take out liver, correspondingly be used for analysis [Dehoff J.L., Clin.Chem., 24,433,1978 of T-CHOL and triglyceride according to the method for Dehoff and Levy; Levy A., Advances in Automated Analysis (Technicon Corp.) 497, Thurman, Miami 1972].Isolate aorta and heart, estimate the situation that exists of atherosclerotic lesions, will damage according to the order of severity and define the level by I-IV according to Klurfeld (Klurfeld D.M., J.Med., 10,35,1979).

These experimental results show; no matter being carnitine or lycopene (degree is a bit weaker) all has protective effect to the cholesterol that caused by high fat diet in the rabbit body and the increase of triglyceride; but only when they unite use, could obtain to protect completely the result.

In fact the animal that crosses with carnitine and lycopene compositions-treated can demonstrate protective effect to a certain degree, and this protective effect is to use adding and being beyond one's reach of effect that single product produces respectively.These experimental results have also proved the significant synergism that combination of the present invention is played.

The experiment that table 4 carries out on one's body the hypercholesteremia rabbit

Plasma lipoprotein concentration

VLDL(mg/dl) LDL(mg/dl) HDL(mg/dl)

HC 1,119±295 485±19.9 23.1±6.5

CM 755±10.9 306±15.5 28.5±5.5

TE 880±105 295±20.7 30.1±4.2

p 805±95 280±22.5 29.5±6.2

L 715±80 260±28.5 29.3±5.5

CM+TE 290±45 155±16.5 35.5±3.9

CM+L 240±25 96±9.4 31.2±29

P+TE 250±30 105±15.5 36.9±3.5

P+L 220 ± 20 90 ± 10.5 32.1 ± 3.1HC=hypercholesteremias contrast CM=carnitine mixture TE=natural tomato carotenoid extract P=propiono L-carnitine L=lycopene

Table 5

On hypercholesteremia rabbit liver, detect

The concentration of T-CHOL and triglyceride

The T-CHOL triglyceride

(mg/dl) (mg/g)

HC 1,885±315 180±15.5

CM 1,420±205 155±12.7

TE 1,475±195 139±11.5

P 1,250±145 142±12.8

L 1,200±180 135±13.8

CM+TE 985±85 115±11.6

CM+L 780±98 105±11.6

P+TE 750±64 110±10.7

P+L 655 ± 90 90 ± 8.5HC=hypercholesteremia contrast CM=carnitine mixture TE=natural tomato carotenoid extract P=propiono L-carnitine L=lycopene

Test with the antiproliferative activity that ODC Ornithine decarboxylase is estimated

As known, can cause and accept the animal skin proliferative disorder handled through the subcutaneous rat phorbol, teleocidin of giving, itself in addition can cause cornea (keratotic) process of tumorous type.Proliferative disorder is attended by the increase of ODC Ornithine decarboxylase, breed under the activatory situation in all pathologic usually, the increase of ornithine decarboxylase activity with cause that the order of severity of damage is proportional.In these experiments, be expelled to the back that mice was pulled out hair under the teleocidin aqueous solution percutaneous with 0.2cc, dosage is 5 a μ g/ mice.In preceding 7 days time of processing; the laboratory animal oral administration is accepted separately by the L-carnitine; acetyl group L-carnitine; propiono L-carnitine; the carnitine mixture (400mg/kg) that isovaleryl L-carnitine is formed; it is consistent that their dosages each other calculate by body weight; or accept propiono L-carnitine (400mg/kg) separately; or accept natural tomato carotenoid extract (100mg/kg separately; wherein contain 5% lycopene); or accept lycopene (5mg/kg) separately; or accept carnitine mixture and lycopene or contain the compositions of lycopene extract, or accept propiono L-carnitine and lycopene or contain the compositions of lycopene extract.In another group experiment, at first product is scattered in the dimethyl sulfoxine, and then be dispersed in the lanoline, up to obtaining concentration is the carnitine mixture of 200mg/cc, or acquisition contains the carotenoid extract that 5% lycopene concentration is 200mg/cc, or after obtaining concentration and being the lycopene of 5mg/cc, before half an hour these products were applied to the skin of mice in the injection teleocidin.

With various preparations with the dose application of 0.3cc in the skin place of injecting teleocidin, with closed binder protection injection site.

For the ODC Ornithine decarboxylase analysis of the skin area of injecting teleocidin, implemented above-mentioned analysis in back 5 hours in injection, this method see O ' Brien and Nakadate (O ' Brien T.G., cancer research, 35,1662,1975; Nakadate T., cancer research, 42,2841,1982) description.Adopt the protein concentration in Lowry method (Lowry O.H., J:Biol.Chem., 193,265,1951) the mensuration epidermis extract.These experimental results show; no matter be that carotenoid in interior alkali or the natural tomato extract and independent propiono L-carnitine and independent lycopene only have very small protective effect to opposing propagation phenomenon and the increase of opposing ornithine decarboxylase activity; in contrast be; when these product mixes are used; effective protective effect but unexpectedly occurred, proved that therefore it has never expectation and beat all synergism.

Table 6

Ornithine decarboxylase activity

Handle ornithine decarboxylase activity

(CO ₂Nmol/60 minute/mg albumen)

The oral administration percutaneous drug delivery

Contrast 0.05 ± 0.002 0.03 ± 0.001

Teleocidin 2.4 ± 0.3 2.6 ± 0.2

Carnitine mixture 1.92 ± 0.4 1.75 ± 0.3

Propiono L-carnitine 1.90 ± 0.2 1.60 ± 0.1

Fructus Lycopersici esculenti natural extract 1.85 ± 0.3 1.80 ± 0.2

Lycopene 1.70 ± 0.1 1.65 ± 0.1

Carnitine mixture+Fructus Lycopersici esculenti natural extract 0.35 ± 0.005 0.40 ± 0.06

Carnitine mixture+lycopene 0.30 ± 0.03 0.45 ± 0.05

Propiono L-carnitine+Fructus Lycopersici esculenti natural extract 0.36 ± 0.06 0.30 ± 0.04

Propiono L-carnitine+lycopene 0.33 ± 0.05 0.31 ± 0.03

Provided illustrative non-limiting example of the present invention below.1) carnitine mixture mg 500

(L-carnitine 125mg, acetyl group L-carnitine 125mg,

Propiono L-carnitine 125mg, isovaleryl L-carnitine

125mg)

Fructus Lycopersici esculenti natural extract (containing 5% lycopene) mg 1002) carnitine mixture mg 300 (L-carnitine 75mg, acetyl group L-carnitine 75mg,

Propiono L-carnitine 75mg, isovaleryl L-carnitine

75mg)

Fructus Lycopersici esculenti natural extract (containing 5% lycopene) mg 503) propiono L-carnitine mg 500

Fructus Lycopersici esculenti natural extract (containing 5% lycopene) mg 1004) propiono L-carnitine mg 250

Fructus Lycopersici esculenti natural extract (containing 5% lycopene) mg 505) propiono L-carnitine mg 500

Lycopene mg 56) propiono L-carnitine mg 250

Lycopene mg 2.57) carnitine mixture mg 300

(L-carnitine 75mg, acetyl group L-carnitine 75mg,

Propiono L-carnitine 75mg, isovaleryl L-carnitine

75mg)

Lycopene mg 58) carnitine mixture mg 300

(L-carnitine 75mg, acetyl group L-carnitine 75mg,

Propiono L-carnitine 75mg, isovaleryl L-carnitine

75mg)

Lycopene mg 2.59) carnitine mixture mg 300

(L-carnitine 75mg, acetyl group L-carnitine 75mg,

Propiono L-carnitine 75mg, isovaleryl L-carnitine

75mg)

The carotenoid complex

(Fructus Lycopersici esculenti, grapefruit, Radix Dauci Sativae, orange blossom natural extract) mg 30010) propiono L-carnitine mg 400

Lycopene mg 2.5

Beta-carotene mg 5

Alpha-carotene mg 2

Lutein mg 5

Cryptoxanthin mg 111) propiono L-carnitine mg 350

Lycopene mg 5

Saw Palmetto Berries (serenoa repens) mg 50

Prunus africana extract mg 5012) carnitine mixture mg 300

(L-carnitine 75mg, acetyl group L-carnitine 75mg,

Propiono L-carnitine 75mg, isovaleryl L-carnitine

75mg)

Fructus Lycopersici esculenti natural extract (containing 5% lycopene) mg 100

Serenoa repens extract mg 50

Prunus africana extract mg 50

XIANTAO (Opuntis ficus indica) extract mg 50

Glycine zinc mg 50

Selenium (1-SLM) μ g 50

Vitamin E mg 10

C ₀Q ₁₀Mg 1013) carnitine mixture mg 400

(L-carnitine 100mg, acetyl group L-carnitine 100mg,

Propiono L-carnitine 100mg, isovaleryl L-carnitine

100mg)

Fructus Lycopersici esculenti natural extract (containing 5% lycopene) mg 100

Extraction is from the anthocyanin mg 50 of raspberry

Extraction is from the polyphenol mg 10 of Fructus Vitis viniferae

Vitamin E mg 10

SLM μ g 5014) propiono L-carnitine mg 300

Beta-carotene mg 5

Lycopene mg 5

Lutein mg 3

Catechin mg 5

Thioctic acid mg 5

C ₀Q ₁₀ mg 10

Vitamin C mg 100

Vitamin PP mg 25

Vitamin B ₆Mg 25

Vitamin B ₁₂μ g 250

Taurine mg 100

The implication of the medicinal salt of L-carnitine or alkanoyl L-carnitine is meant any salt that these active component and acid form, and described acid can not produce toxicity or the side effect that does not expect to have.These acid are known for the medicine expert.

The infinite example of suitable salt is as follows: chloride; Bromide; Iodide; Aspartate, acid aspartate; Citrate, acid citrate; Tartrate; Phosphate, superphosphate; Fumarate, acid fumarate; Phosphoglycerol; Glucose 1-phosphate1-; Lactate; Maleate; Acid maleate; Orotate; Salt of sorrel; Sulfate, hydrosulphate; Trichloroacetate; Trifluoroacetate and mesylate.

Int.J.of Pharm.38, (1986) have provided the medicinal salts catalog that FDA permits among the 201-217; This nearest publication is used as list of references and introduces.

Compositions of the present invention also comprises vitamin, isozyme, mineral and antioxidant.The suitable excipient that is used for preparing the compositions that is used for the particular approach administration is conspicuous for the expert of medicine and food industry.

Claims

1. compositions, it comprises:

(a) propiono L-carnitine or its pharmacology go up acceptable salt; And

(b) carotenoid.

2. the compositions described in the claim 1, wherein composition (a) further comprises " carnitine " below being selected from down: L-carnitine, acetyl group L-carnitine, valeryl L-carnitine, isovaleryl L-carnitine or their medicinal salts or their mixture.

3. the compositions described in the claim 1 or 2, carotenoid wherein is selected from lycopene, alpha-carotene, beta-carotene, cryptoxanthin, kryptoxanthin, lutein or their mixture.

4. the compositions described in the claim 1-3, wherein (a): ratio (b) is 1: 0.1 to 1: 10.。

5. the compositions described in any aforementioned claim, wherein composition (b) is that form with vegetable extract exists, this extract contains composition itself.

6. the compositions described in the claim 5, wherein said vegetable extract is a Fructus Lycopersici esculenti extract.

7. the compositions described in the claim 6, wherein said Fructus Lycopersici esculenti extract contains the lycopene of the 2-20% that has an appointment.

8. the compositions described in any aforementioned claim, wherein L-carnitine or alkanoyl L-carnitine pharmaceutical salts are selected from following compounds: chloride; Bromide; Iodide; Aspartate, acid aspartate; Citrate, acid citrate; Tartrate; Phosphate, superphosphate; Fumarate, acid fumarate; Phosphoglycerol; Glucose 1-phosphate1-; Lactate; Maleate; Acid maleate; Orotate; Salt of sorrel; Sulfate, hydrosulphate; Trichloroacetate; Trifluoroacetate and mesylate.

9. the compositions described in any aforementioned claim, it further comprises vitamin, isozyme, mineral and antioxidant.

10. the compositions described in any aforementioned claim, its form with diet supplement is carried out oral administration.

11. the compositions described in any aforementioned claim, the form that it can medicine, oral administration, non-intestinal, rectum, skin is saturating or eye instils carries out administration.

12. the diet supplement described in the claim 10, it can be used for preventing the fat peroxidating phenomenon by environmental pollution and atherosclerosis, blood vessel, heart or brain to cause free radical to have the disease that is produced; The propagation change of tissue comprises prostate, uterus, breast or colon; Vision and retina change comprise cataract and the degeneration of amphiblestroid speckle.

13. the medicine described in the claim 11, its fat peroxidating phenomenon that can be used for treating by environmental pollution and atherosclerosis, blood vessel, heart or brain causes free radical to have the disease that is produced; The propagation change of tissue comprises prostate, uterus, breast or colon; Vision and retina change comprise cataract and the degeneration of amphiblestroid speckle.

14. the diet supplement described in the claim 12, it exists with solid, semisolid or liquid form.

15. the medicine described in the claim 13, it exists with solid, semisolid or liquid form.

16. the diet supplement described in the claim 14, it exists with forms such as tablet, lozenge, pill, capsule, granule or syrups.

17. the medicine described in the claim 13, it exists with tablet, lozenge, pill, capsule, granule, syrup, bottle, collyrium and forms such as eye abluent or drop.