Antioxidant

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to an antioxidant containing a cyclolanostan derivative selected from 9,19-cyclolanostan-3-ol and 24-methylene-9,19-cyclolanostan-3-ol, and a lophenol derivative selected from 4-methylcholest-7-en-3-ol, 4-methylergost-7-en-3-ol and 4-methylstigmast-7-en-3-ol, in the concentration of min. 0.0001 wt %, as an active ingredient. The invention also concerns a method for preparing the specified antioxidant. The antioxidant may be used as a drug preparation, a food or a beverage, a food additive, a drug preparation for topical skin application.

EFFECT: mentioned antioxidant provides the inhibition of lipid peroxide formation.

28 cl, 2 tbl, 2 ex

 

The technical field to which the invention relates

The present invention relates to antioxidant that can be used as a drug, food product or beverage, dietary supplements, medication for local application on the skin, etc.

The level of technology

“Oxidative stress” is defined as a condition in which a living organism is oxidative trend as a result of imbalance between production of reactive oxygen compounds (ROS) and antioxidant defense mechanisms in vivo. That is, excessive production of ROS or a decrease in antioxidant capacity leads to oxidative stress.

ROS oxidize lipid, in particular low-density lipoprotein (LDL) phospholipid with the formation of lipid peroxide and oxidized LDL and oxidative way denaturised and deactivates the protein, causing oxidative DNA damage. Therefore believe that oxidative stress is involved in the development of many diseases, such as arteriosclerosis, cancer, various diseases associated with quality of life, Alzheimer's disease and Parkinson's disease, and accelerates aging because of damage to cells and tissues and weakens the vital functions (see, for example, non-patent document 1).

In addition, the skin is in a state in which RS is easily reproduced by irradiation of the environmental factor, such as ultraviolet rays. ROS in the skin causes, for example, the destruction of body tissue, such as collagen, to cell damage, leading to such symptoms of aging, such as wrinkles, loss of firmness, inflammation, and pigmentation. In addition, it is known that ROS oxidizes proteins and lipids in the scalp, causing hair loss (see, for example, patent documents 1 and 2).

Meanwhile, it is known that if the peroxide concentration of lipid increases in the blood itself peroxide lipid or the product of its oxidative decomposition acts directly on nucleic acids and proteins, causing angiopathy, liver dysfunction, cataracts, or the like. In addition, lipid peroxide damage vascular endothelial cells, increased platelet aggregation, the formation of foam cells or the like and is therefore considered that it is called arteriosclerosis.

For example, it is known that the initial lesion of arteriosclerosis is caused by oxidized low-density lipoprotein (LDL), and that the easiest way of detecting oxidation of LDL is the measurement of lipid peroxide (see, for example, non-patent document 2).

As antioxidants from natural products known vitamin E, vitamin C, neutral fraction of the extract of the plantHelichrysum(see, for example, patent on the document 1), extract ofChimaphila umbellata(see, for example, patent document 2), and the like.

In particular, a known drug or similar means for inhibiting formation of a lipid peroxide in vivo include agent containing sesamin and/or apiname as an active ingredient (see, for example, patent document 3), the agent is characterized by the content of fructo-oligosaccharide (see, for example, patent document 4), the agent containing as an active ingredient an extract obtained by extraction from the leaves of Psidium guajava L. (see, for example, patent document 5), an agent for inhibiting formation of a lipid peroxide, characterized by a content of the extract of the herb, native to Mexico scientific nameGnaphalium semiamlexicaule(see, for example, patent document 6), the agent containing astaxanthin and/or its ester (see, for example, patent document 7), and an agent containing as an extract ofApocynum venetum L., and vitamin C (see, for example, patent document 8).

In addition, in patent document describes an application as agent for the prevention and treatment of hyperlipemia γ-oryzanol, which is a mixture of compounds obtained by the independent binding of campestrini, β-sitosterol, cycloartenol, 24-methylenecycloartanol and cyclobutanol with ether ferulovoi acid. The patent is a document 10 describes one introduction of any of cycloartenol and 24-methylcyclopentanol reduces cholesterol level in blood plasma and reduce the level of cholesterol high-density lipoprotein (HDL-C) and leads to a significant change in TG, PL and LPO.

In addition, developed antioxidants such as 3,5-tert-butyl-4-hydroxytoluene (EIT) and 2,3-tert-butylhydroxyanisole (BHA), for inhibition of lipid oxidation or the like. However, these antioxidants may be carcinogens (see, for example, non-patent document 3), and it is difficult to use safely.

Under such circumstances, it would be desirable to develop a new antioxidant substance that could be applied safely and which has no side effects.

It should be noted that a known agent for improvement in hyperglycemia, the agent for improving pancreatic functions, agent for improvement in insulin resistance and the agent for inhibiting visceral accumulation of fat, each of which contains a derivative of cyclopentane, such as 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, or derived latinola, such as metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol or 4-methylstyryl-7-EN-3-ol as an active ingredient (as in patent documents 11 to 13, patent documents 14 and 15 of the patent the documents 16 and 17 and patent document 18, respectively.

The documents of the prior art

Patent documents

[Patent document 1] JP-A-2007-016077

[Patent document 2] JP-A-2004-149729

[Patent document 3] JP-A-5-51388

[Patent document 4] JP-A-8-325157

[Patent document 5] JP 11-75770

[Patent document 6] JP-A-2000-198726

[Patent document 7] JP-A-2006-8719

[Patent document 8] JP-A-2006-160668

[Patent document 9] JP 06-298645 A

[Patent document 10] JP 05-33713 B2

[Patent document 11] WO 2007/060911 A1

[Patent document 12] WO 2006/035525 A1

[Patent document 13] WO 2005/094838 A1

[Patent document 14] WO 2005/123466 A1

[Patent document 15] WO 2005/123465 A1

[Patent document 16] WO 2007/043306 A1

[Patent document 17] WO 2007/043305 A1

[Patent document 18] WO 2007/043294 A1

Non-patent documents

[Non-patent document 1] YAKUGAKU ZASSHI, 127(12) 2007, 1997-2014

[Non-patent document 2] "Oxidative Stress Navigator", Masahiko Kurabayashi, Ed., Medical Review Co., Ltd., 2005, 192-193

[Non-patent document 3] Cancer Research, 44, 1984, 1604-1610

The invention

The present invention is the provision of an antioxidant which is highly safe, inhibit the oxidation of a biological component, especially lipid, and which can be used as a drug, food product or beverage, dietary supplements, medication for local application to the skin or the like. In particular, the present invention is the provision of medicines, food product or beverage or the like for inhibiting the formation of lipid peroxide and effectively inhibiting the formation of lipid peroxide in blood.

The first invention for resolving the above problems is an antioxidant containing a compound selected from a derivative of cyclopentane and derived latinola as an active ingredient (hereinafter referred to as the antioxidant of the present invention, this invention includes the following preferred embodiments of(1)-(9):

(1) the antioxidant-containing derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9;

(2) the antioxidant-containing compound selected from a derivative of cyclopentane and derived latinola at a concentration of at least 0.0001 wt.%;

(3) antioxidant containing derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol;

(4) an antioxidant, containing the derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol;

(5) an antioxidant used for the inhibition of lipid oxidation;

(a) an antioxidant, used for inhibiting the formation of lipid peroxide;

(7) an antioxidant, which is a preparation for topical application to the skin;

(8) an antioxidant consisting of a food or drink containing a compound selected from a derivative of cyclopentane and derived latinola; and

(9) an antioxidant, emulsifier.

The second invention for resolving the above problems is a method of making an antioxidant, which comprises mixing with the use of compounds selected from a derivative of cyclopentane and derived latinola, as an active ingredient. Preferred embodiments of compounds are the same as preferred embodiments of the first invention.

The first invention includes, as an option for implementation of the drug for inhibiting formation of a lipid peroxide, which contains a compound selected from a derivative of cyclopentane and derived latinola as the active ingredient. An implementation option includes the following preferred embodiments of(10)-(13):

(10) a drug containing derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9;

(11) a drug containing a compound selected from a derivative of cyclopentane and derived latinola at a concentration of at least 0.0001 wt.%;

(12) the drug-containing derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol; and

(13) a drug containing derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol.

The second invention includes as a variant implementation of the method of manufacture of a medicine for inhibiting formation of a lipid peroxide, and the method includes mixing with the use of compounds selected from a derivative of cyclopentane and derived latinola, as an active ingredient. Preferred embodiments of compounds of this embodiment are the same as preferred embodiments of described above.

The first invention includes, as an option for implementation of food or drink for inhibiting formation of a lipid peroxide, which contains a compound selected from a derivative of cyclopentane and derived latinola as the active ingredient. An implementation option includes the following preferred the embodiments of sustained fashion(14)-(20):

(14) food or drink containing a derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9;

(15) a food or drink containing a compound selected from a derivative of cyclopentane and derived latinola at a concentration of at least 0.0001 wt.%;

(16) food or drink containing a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol;

(17) food or drink containing the derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol;

(18) food or drink, optionally containing emulsifier;

(19) a food or drink containing fat and oil; and

(20) food or drink, which is a functional food product or beverage.

The second invention includes as a variant implementation of the method of manufacturing a food or drink for inhibiting formation of a lipid peroxide, which comprises mixing with the use of compounds selected from a derivative of cyclopentane and derived latinola as the active ingredient. Preferred embodiments of the compounds in this embodiment, the wasp is estline are the same as preferred embodiments of described above.

The first invention includes, as an option for implementation of the food additive for inhibiting formation of a lipid peroxide, which contains a compound selected from a derivative of cyclopentane and derived latinola as the active ingredient. An implementation option includes the following preferred embodiments of(21)-(25):

(21) a food additive, optionally containing emulsifier;

(22) a dietary Supplement containing a derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9;

(23) a dietary Supplement containing a compound selected from a derivative of cyclopentane and derived latinola, at a concentration of at least 0.001 wt.%;

(24) a dietary Supplement containing a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol; and

(25) a dietary Supplement containing derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol.

The second invention includes as a variant implementation of the method of manufacture of food additives for inhibiting formation of a lipid peroxide, and the method includes smesi the use of application connections selected from a derivative of cyclopentane and derived latinola, as an active ingredient. Preferred embodiments of compounds of this embodiment are the same as preferred embodiments of described above. An implementation option of mixing with the participation of the emulsifier is preferred.

Further, the third invention for resolving the above problem is the use of compounds selected from a derivative of cyclopentane and derived latinola, in the manufacture of antioxidant. Preferred embodiments of compounds are the same as preferred embodiments of the first invention.

Further, the third invention includes the following options:

(26) used in the manufacture of an antioxidant composition containing a derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9;

(27) used in the manufacture of an antioxidant composition comprising a compound selected from a derivative of cyclopentane and derived latinola, at a concentration of at least 0.0001 wt.%.

The third invention includes as an option the implementation of the application connection, you the security of a derivative of cyclopentane and derived latinola, in the manufacture of a medicine for inhibiting formation of a lipid peroxide. Preferred embodiments of compounds are the same as preferred embodiments of the first invention.

Next, an implementation option includes the following options:

(28) used in the manufacture of a medicine for inhibiting the formation of lipid peroxide compositions containing a derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola = 6,3:2,7-5,1:4,9; and

(29) used in the manufacture of a medicine for inhibiting the formation of lipid peroxide compositions containing a compound selected from a derivative of cyclopentane and derived latinola, at a concentration of at least 0.0001 wt.%.

The third invention includes, as an option for implementation of the use of compounds selected from a derivative of cyclopentane and derived latinola, in the manufacture of food or drink for inhibiting formation of a lipid peroxide. Preferred embodiments of compounds of this embodiment are the same as preferred embodiments of the first invention.

Next, Varian is the implementation includes the following options:

(30) used in the manufacture of food and drink for inhibiting formation of a lipid peroxide compositions containing a derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola = 6,3:2,7-5,1:4,9; and

(31) the use of a composition containing a compound selected from a derivative of cyclopentane and derived latinola, at a concentration of at least 0.0001 wt.%, in the manufacture of food or drink for inhibiting formation of a lipid peroxide.

The third invention also includes as an option for implementing the use of compounds selected from a derivative of cyclopentane and derived latinola, in the manufacture of food supplements for inhibiting formation of a lipid peroxide. Preferred embodiments of compounds are the same as preferred embodiments of the first invention.

Next, an implementation option includes the following options:

(32) used in the manufacture of food supplements for inhibiting the formation of lipid peroxide compositions containing a derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola = 6,3:2,7-5,1:4,9; and

(33) when is the change of the composition, containing a compound selected from a derivative of cyclopentane and derived latinola, at a concentration of at least 0.001 wt.% in the manufacture of food supplements for inhibiting formation of a lipid peroxide.

Further, the fourth invention for resolving the above problems is a compound which is selected from a derivative of cyclopentane and derived latinola and which is used in anticyclone. Preferred embodiments of compounds are the same as preferred embodiments of the first invention. The above connection is preferred for use in the inhibition of lipid oxidation and preferred for use in the inhibition of the formation of a lipid peroxide.

The fourth invention includes as an option the implementation of the composition for use in inhibiting the formation of lipid peroxide, which contains a compound selected from a derivative of cyclopentane and derived latinola. Preferred embodiments of the composition include the following options:

(34) a composition comprising a compound selected from a derivative of cyclopentane and derived latinola, and emulsifier;

(35) a composition comprising a compound selected from the derived Cicala is austan and derived latinola, when the next mass ratio: derived cyclopentane:derived latinola = 6,3:2,7-5,1:4,9; and

(36) a composition comprising a compound selected from a derivative of cyclopentane and derived latinola, at a concentration of at least 0.0001 wt.%.

Further, the fifth invention for resolving the above problems is a method of treating or preventing the disease or symptom that is related to oxidation, and the method includes the introduction of compounds selected from a derivative of cyclopentane and derived latinola, the entity that needs anticyclone. Preferred embodiments of compounds are the same as preferred embodiments of the compound of the first invention.

Further, the fifth invention includes the following preferred embodiments of(37)-(39):

(37) introduction derivative of cyclopentane and derived latinola at the following mass ratio: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9;

(38) the introduction of a composition containing a derivative of cyclopentane and derived latinola when the mass ratio described above; and

(39) the introduction of a composition containing a compound selected from a derivative of cyclopentane and derived latinola, at a concentration of at least 0.0001 wt.%.

Next,a sixth invention for resolving the above problems is a method of imparting anti-oxidant activity of the food product or beverage, moreover, the method includes adding a compound selected from the derived cyclopentane and derived latinola, food product or beverage, so that the total concentration of compounds in the food product or beverage was at least 0.0001 wt.%. Preferred embodiments of compounds are the same as preferred embodiments of the compound of the first invention.

Next, the seventh invention for resolving the above problems is a method of improving the antioxidant activity of food or drink containing a compound selected from a derivative of cyclopentane and derived latinola, and the method comprises adding a compound selected from the derived cyclopentane and derived latinola, food product or beverage, so that the total concentration of compounds in the food product or beverage was at least 0.0001 wt.%. Preferred embodiments of compounds are the same as preferred embodiments of the compound of the first invention.

The antioxidant of the present invention can be applied in various forms, including drug, food product or beverage, food additive, drug for topical application to the skin, and this antioxidant-ingibiruet the oxidation of a biological component, in particular, the oxidation of lipid.

The drug of the present invention can be safely enter and it inhibits the oxidation of a biological component, in particular the formation of lipid peroxide in blood. In addition, food product or beverage of the present invention can be consumed safely and effectively inhibits the oxidation of a biological component, in particular the formation of lipid peroxide in blood. In addition, a food additive of the present invention is suitable for manufacturing the above food product or beverage, or to prevent oxidation of the component in the food product or beverage. In addition, the preparation for topical application to the skin of the present invention can be applied safely, and it inhibits the oxidation component of the skin, in particular the formation of lipid peroxide in the skin.

Next, the active ingredient in the antioxidant of the present invention, derived cyclopentane or derived latinola can be obtained by chemical synthesis, and according to the production method of invention of the present application, the antioxidant of the present invention can be obtained easily. In addition, it is known that the active ingredient in the antioxidant of the present invention is safe on the basis of these tests food and his mo is but easily obtained from plants of the family Liliaceaethat is easily accessible such plants, asAloe barbadensis Miller. Consequently, according to the production method of an invention of this application, you can easily get the antioxidant of the present invention.

Description of embodiments

In further preferred embodiments of the present invention are described in detail. However, the present invention is not limited to the following preferred options for implementation, and can be done any modification within the scope of the present invention. It should be noted that in this specification, all percentages are given as weight percents unless otherwise specified.

The antioxidant of the present invention contains a compound selected from a derivative of cyclopentane and derived latinola, as an active ingredient.

[Derived cyclopentane]

Derived cyclopentane (compound having a skeleton of cyclopentane) represented by the following General formula (1).

(1)

In the General formula (1) R1 represents an alkyl group or alkenylphenol group containing one or two double bonds, which is unbranched or branched chain, containing from 6-8 carbon atoms, or substituted alkyl or alkenylphenol group received Zam the Noah one or two hydrogen atoms of the above alkyl and alkenyl groups on the hydroxyl group and/or carbonyl group, each of R2 and R3 independently represents a hydrogen atom or methyl group, and R4 forms C=O with the carbon atom forming part of a ring, or represents any of groups of the following formulas.

In the General formula (1) R1 preferably represents any of groups represented by the following formulas.

-CH2-CH2-CH2-CH(CH3)2

-CH2-CH2-CHRa-C(CH3)2Rb

(where Ra represents a hydrogen atom, a hydroxyl group or methyl group, and Rb represents a hydrogen atom or hydroxyl group),

-CH2-CH2-CH(CH2CH3)-CH(CH3)2

-CH2-CH2-CHRc-C(CH3)=CH2

(where Rc represents a hydrogen atom, a hydroxyl group or methyl group)

-CH2-CH2-C(=O)-C(CH3)=CH2

-CH2-CH2-C(=CH2)-CH(CH3)2

-CH2-CH2-CH=C(CH3)2

-CH2-CH=C(CH3)-CH(CH3)2

-CH2-CH2-C(=CHCH3)-CH(CH3)2.

Preferred examples derived cyclopentane include 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol.

These derivatives have the structure represented by the following formulas (2) and (3) respectively.

Faure is ula (2): 9,19-cyclopentan-3-ol

Formula (3): 24-methylene-9,19-cyclopentan-3-ol

Derived cyclopentane can be obtained by a chemical process according to a known method of obtaining. For example, 24-methylene-9,19-cyclopentan-3-ol (common name: 24-methylenecycloartanol)represented by the formula (3), can be obtained by the method described in JP 57-018617 A. in Addition, a derivative of cyclopentane can be obtained by the method described in JP 2003-277269 But using as the starting material of the hydrolyzate of ferulate of cycloartenol (formula (4)) of γ-oryzanol.

Formula (4): Perolat of cycloartenol

It is known that the derivative of cyclopentane contained in the plant, belonging to the familyLiliaceae, familyLeguminosae, familyGramineae, familySolanaceaeor familyMusaceae(see [Phytochemistry, USA, 1977, vol.16, pp.140-141], [Handbook of phytochemical constituents of GRAS herbs and other economic plants, 1992, USA, CRC Press] or [Hager''s Handbuch der Pharmazeutischen Praxis, vol.2-6, 1969-1979, Germany, Springer-Verlag, Berlin]). Therefore, the connection can be extracted from these plants in such a way as extraction with an organic solvent or extraction with hot water.

In addition, derived cyclopentane can be obtained by biological method using microorganism or similar. Or the same compound can be obtained by application of the enzyme obtained the CSOs of the microorganism.

The molecular weight, structure and the like of the compound obtained as described above, it is possible to determine or confirm, for example, mass spectrometry (MS) spectrometry and nuclear magnetic resonance (NMR).

In addition, a derivative of cyclopentane may be pharmaceutically acceptable salt. Pharmaceutically acceptable salt includes a salt of metal (inorganic salt)and organic salt. Examples include salts described in Remington's Pharmaceutical Sciences, 17th edition, 1985, p. 1418.

Specific examples of salts include, but are not limited to, inorganic salts such as hydrochloride, sulfate, phosphate, diphosphate, hydrobromide and sulfate; and salts of organic acids such as malate, maleate, fumarate, tartrate, succinate, citrate, acetate, lactate, methanesulfonate, p-toluensulfonate, pamoate, salicylate and stearate.

Meanwhile, the salt may be a salt of a metal, such as sodium, potassium, calcium, magnesium or aluminum, or a salt of the amino acids such as lysine. In addition, you can also use the MES, such as a hydrate, the above compound or its pharmaceutically acceptable salt.

[Derived latinola]

Derived latinola (compound having a skeleton of latinola) represented by the following General formula (5).

(5)

In the General formula (5) R1 before the hat is alkyl group or alkenylphenol group, containing one or two double bonds, which is unbranched or branched chain, containing 5-16 carbon atoms. Alkyl or Alchemilla group may be substituted by alkyl or alkenylphenol group formed by replacing at least one hydrogen atom on the hydroxyl group and/or carbonyl group. Each of R2 and R3 independently represents a hydrogen atom, alkyl group or substituted alkyl group having 1-3 carbon atoms; and R4 forms C=O with the carbon atom forming part of a ring, or is it a HE or OSON3. Alkyl group having 1-3 carbon atoms, is preferably a methyl group, ethyl group, or so on, particularly preferably a methyl group.

In the General formula (5) R1 preferably represents any of groups represented by the following formulas.

-CH2-CH2-CH(-CH2-CH3)-CH(CH3)2

-CH2-CH2-CH=C(CH3)2

-CH2-CH=C(CH3)-CH(CH3)2

-CH2-CH2-C(=CH-CH3)-CH(CH3)2

-CH2-CH2-CH(Ra)=C(CH3)Rb

(where Ra and Rb represent any of the radicals-H, -OH or-CH3)

-CH2-CH2-CH(Rc)-CH(CH3)Rd

(where Rc and Rd represent any of the radicals-H, -OH or-CH3).

Preferred examples of p is vizvolnogo of latinola include 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol.

These derivatives have the structure represented by the following formulas (6)-(8), respectively.

Formula (6): 4-metalholic-7-EN-3-ol

Formula (7): 4-metalurgist-7-EN-3-ol

Formula (8): 4-methylstyryl-7-EN-3-ol

It is known that the derived latinola like derived cyclopentane found in plants and can be obtained with the use of plants as source material according to a known method for obtaining latinola (see, for example, JP 3905913). In addition, the derived latinola can be synthesized according to, for example, the additional data described in Vitali Matyash et al., PLOS BIOLOGY, Volume 2, Issue 10, e280, 2004.

The molecular weight, structure and the like of the compound obtained as described above, it is possible to determine or confirm, for example, mass spectrometry (MS) spectrometry and nuclear magnetic resonance (NMR).

In addition, a derivative of latinola may be pharmaceutically acceptable salt. Pharmaceutically acceptable salt include salts, as salts in the case of derived cyclopentane.

The antioxidant of the present invention

The antioxidant of the present invention contains a compound selected from the derived cyclorana the Tana and derived latinola, as the active ingredient. The connection can be one or more kinds of compounds.

The antioxidant of the present invention preferably contains in combination as a compound selected from a derivative of cyclopentane, and a compound selected from the derived latinola. Each of the derived cyclopentane and derived latinola may be one or more kinds of compounds.

In this case, the mass ratio derived cyclopentane and derived latinola is preferably in the following range: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9.

A specific range of mass relations almost corresponds to the mass ratio of the derivatives of cyclopentane (in particular, 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol) and derived latinola (in particular, 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol) in naturalAloe barbadensis Miller.

The concentration of compounds selected from a derivative of cyclopentane and derived latinola, the antioxidant of the present invention can appropriately be selected depending on which is the purpose of treating diseases or entity who enter the connection. The total concentration is preferably at least 0.0001 wt.%, more preferably by less than the least 0.001 wt.%, even more preferably at least 0.005 wt.% or particularly preferably at least 0.01 wt.%. In addition, the upper limit to the total concentration of compounds in medicinal agent of the present invention is not specifically limited and, for example, the concentration of 90 wt.% or less, preferably 70 wt.% or less and more preferably 50 wt.% or less.

The antioxidant of the present invention can be applied in the form of medicines, food product or beverage, dietary supplements, medication for local application to the skin or the like.

The drug of the present invention

The antioxidant of the present invention in the form of a medicinal product (“called drug of the present invention”) can be administered orally or parenterally to a mammal, including man.

The drug of the present invention can be applied for the prevention and/or treatment of a disease or symptom attributed to oxidation of a biological component, such as a lipid, in particular the formation of lipid peroxide. Examples of such disease or symptom include arteriosclerosis, cerebral hemorrhage, angina, myocardial infarction, liver dysfunction, cirrhosis, hepatitis, retinopathy, cataracts, sickness Alch is imera, Parkinson's disease, allergic disease, cancer, roughness, aging, atopic dermatitis, and skin pigmentation, such as spots and freckles, wrinkles and decreased elasticity of the skin, alopecia, rheumatoid arthritis, Bechet disease, and other violations of tissue stiffness and excessive sensitivity to cold shoulder. Of these diseases and symptoms, the drug of the present invention particularly exhibits a significant effect in the prevention and/or treatment of arteriosclerosis, angina and myocardial infarction.

In addition, the drug of the present invention is applicable to the individual in need of preventing illness or reducing the risk of occurrence of such cases, i.e. the individual with the risk of increased content of lipid peroxide in a living organism.

Dosage form of the present invention, in particular, is not limited and can be selected depending on therapeutic purpose or regimens medication. Specific examples include tablet, pill, powder, liquid, suspension, emulsion, granule, capsule, syrup, suppository, injection, ointment, plaster, ophthalmic solution and nasal drops.

The time of introduction of the drug of the present invention, in particular, not ogran is ensured and can be appropriately selected depending on which is the goal of treatment of the disease. Meanwhile, the dose is preferably determined depending on the dosage form, regimen medicines, age and sex of the patient, other conditions, severity of the symptom or the like.

The dose of the drug of the present invention is appropriately selected depending on the regimen of medicines, age or sex of the patient, severity of symptoms, other conditions or the like. The dose is usually in the range of preferably 0.001 to 50 mg/kg/day, or more preferably 0.01 to 1 mg/kg/day in terms of the amount of the active ingredient.

Therefore, one of the preferred embodiments of the medicinal product of the present invention is a medicinal product, which is applied to a compound selected from a derivative of cyclopentane and derived latinola, was introduced in the total amount of preferably 0.001 to 50 mg/kg/day, or more preferably 0.01 to 1 mg/kg/day.

The drug of the present invention may contain additives which are usually used for medicines for inhibiting formation of a lipid peroxide. Examples of the additives include a filler, binder, disintegrity agent, lubricating agent, stabilizer, corrigent, diluent, surfactant and dissolve the eh for injection. In addition, the drug of the present invention may contain the active ingredients, corresponding to the disease or symptoms that prevent or treat, for example, other ingredients, each of which has an effect on improvement and/or prevention of arteriosclerosis, cerebral hemorrhage, hepatic dysfunction, or the like, provided that the antioxidant activity derived cyclopentane and derived latinola not weakened.

The drug of the present invention can be produced by mixing used as the active ingredient compounds selected from a derivative of cyclopentane and derived latinola, with a carrier for drugs. The drug of the present invention can be produced, for example, by mixing the above compounds described above with the addition.

Further, the drug of the present invention can be produced by mixing the extract, which is obtained by extraction using hot water or other solvent, supercritical extraction or subcritical extraction with the use of known plants containing the above compound as a starting material, the above-mentioned additive.

In particular, drug medium is in the present invention, which contains a derivative of cyclopentane and derived latinola at a specific mass ratio within the above range, can be produced by mixing the compounds with a mass ratio within the above limit. Further, this drug can be manufactured in such a way as extraction using different solvents, supercritical extraction or subcritical extraction with the use of known plants containing derivative of cyclopentane and derived latinola, or the like as the starting material.

The drug of the present invention can be produced by supercritical extraction of powderedAloe barbadensismesophyll, which is obtained by freeze drying or by drying with hot air part of theAloe barbadensismesophyll (clear gel)that does not contain the skin of the leaves.

In this case, to improve the efficiency of extraction derived cyclopentane and derived latinola as solvent for extraction can be applied supercritical propane, supercritical ethylene, supercritical 1,1,1,2-Tetrafluoroethane or the like. However, for increased security, it is preferable to use carbon dioxide. In addition, the temperature of extraction can appropriately be selected in the temperature range of the 28°C to 120°C. However, to increase the efficiency of extraction derived cyclopentane and derived latinola and to reduce the extracted number antrahinonovye compounds with laxative properties (such as aloe-emodin), the extraction is preferably carried out within a temperature 50-69°C or more preferably 50-59°C. the Pressure can be appropriately selected in the range of 5.5 to 60 MPa. However, to increase the efficiency of extraction derived cyclopentane and derived latinola and to reduce the content antrahinonovye connection extraction is performed at a pressure in the range of preferably 15-60 MPa or more, preferably 15 to 24 MPa. In addition, to improve the efficiency of extraction derived cyclopentane and derived latinola you can use such a solvent, forming azeotropic mixture as ethanol. However, to reduce the extracted number antrahinonovye connection when the extraction is preferably not applied solvent, forming azeotropic mixture.

The drug of the present invention can be applied separately or together with the agent for the prevention/treatment of a known disease, what is described above. If the drug is used in conjunction with this agent, the action for the prevention/treatment of the above for which Alemania can be improved. The agent for the prevention/treatment of the above diseases, which is used together with a drug of the present invention may be contained in a medicinal product of the present invention as an active ingredient, or can be sold as a single agent, without adding it to the drug of the present invention to obtain a set that includes drug and the above agent to apply them in combination.

The drug of the present invention has an excellent inhibitory effect on the formation of lipid peroxide due to the antioxidant activity of a compound selected from the derived cyclopentane and derived latinola.

Food or drink of the present invention

When the antioxidant of the present invention used in the form of food or drink (called “food product or beverage of the present invention”) is a food product or beverage can be applied to reduce the risk of disease or symptom that is related to the oxidation of a biological component, such as a lipid, especially the formation of lipid peroxide, or for the prevention of such disease or symptom.

Food or drink of the present invention contains a compound selected is derived from cyclopentane and derived latinola, as the active ingredient.

In the present invention the food product or beverage” includes not only food or drink that is consumed by humans, but also food that is consumed by animals, other than man.

Food or drink of the present invention preferably contains in combination as a compound selected from a derivative of cyclopentane, and a compound selected from the derived latinola. Each derived cyclopentane and derived latinola may be one or more kinds of compounds.

In this case, the mass ratio derived cyclopentane and derived latinola is preferably in the following range: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9.

The concentration of compounds selected from a derivative of cyclopentane and derived latinola, in the food product or beverage of the present invention appropriately set depending on the shape of the food product or beverage. The total concentration preferably is preferably at least 0.0001 wt.%, more preferably at least 0.001 wt.%, even more preferably at least 0.005 wt.% or particularly preferably at least 0.01 wt.%. The upper limit of the concentration of the compound in Peshev is m the food or beverage of the present invention is not specifically limited, and, for example, the total concentration of 90 wt.% or less, preferably 70 wt.% or less, or more preferably 50 wt.% or less.

Further, the concentration of compounds selected from a derivative of cyclopentane and derived latinola, in the food product or beverage of the present invention can be set so that the total amount that is suitable for consumption was in the range of 0.001-50 mg/kg/day, or more preferably 0.01 to 1 mg/kg/day, depending on the shape of the food product or beverage. Therefore, one of the preferred embodiments the food product or beverage of the present invention is a food product or beverage, which is used so that a compound selected from a derivative of cyclopentane and derived latinola, you could consume in the total amount of preferably 0.001 to 50 mg/kg/day, or more preferably 0.01 to 1 mg/kg/day.

Food or drink of the present invention preferably further comprises an emulsifier. The emulsifier is not specifically limited, provided that it can be used in the food product. Preferably used, for example, emulsifiers, which are permitted for use as food additives in Japan, such as the ester of glycerol and fatty acid ester of sucrose and fatty acids, ether sorbitan and fat is Oh acid, ether of propylene glycol and fatty acids and lecithins.

Food or drink, optionally containing emulsifier, has a high capacity for dispersing a compound selected from a derivative of cyclopentane and derived latinola, and can provide its action is very stable.

Further, if a compound selected from a derivative of cyclopentane and derived latinola, you can enter into the food or drink containing fat and oil, or preferably a food product or a beverage containing fat and oil as a main component, it is possible to obtain a food or drink having excellent storage stability due to the fact that inhibited its spoilage due to oxidation of lipid. The content of the above compounds or the mass ratio derived cyclopentane and derived latinola in the case of mixing of these derivatives is the same as described above. In addition, such a food product or a beverage, preferably emuleret. Examples of the food or beverage containing fat and oil include edible oil, seasoning to the meat, mayonnaise, butter, margarine and cream. Emulsified food product preferably contains an emulsifier. The preferred emulsifiers are emulsifiers specified above.

Ishenim product or beverage of the present invention preferably is a functional food product or a beverage.

“Functional food product or beverage” means a food product that directly or indirectly reveals the effect on prevention of the disease or the action to decrease the risk of developing the disease. Examples include food products that are now sold in Japan as a food for use in a particular state of health and medical supplements.

Examples of the shape of the food product or beverage of the present invention include beverages such as soft drink, carbonated drink, nutritious drink, drink fruit juice and drink with lactic acid bacteria (including concentrated source solutions of these drinks and powders for making such drinks; frozen foods such as ice cream, sherbet (sorbet and ice shavings; noodles such as Japanese noodles with the addition of buckwheat, wheat noodles, bean-starch vermicelli, fruit, baked in pastry, wrap the product su my, Chinese noodles and bystrorazvarivayuschayasya noodles, confectionery products such as candy, chewing gum, candy, gum, chocolate, confection in the form of tablets, dry Breakfast, biscuit, jelly candies, jam, cream and baked confection; affected by technological processing the seafood and meat products, such as boiled fish paste, ham, and sausage; dairy products such as processed milk, milk beverages, milk and butter; dairy dish and baked goods; other foods or drinks, such as nutritious food, liquid food product, milk for baby food and drink for athletes.

In particular, a functional food product or beverage preferably has the form of granules, tablets or liquid supplements, and therefore the individual who consumes the food product can easily know the amount of the active ingredient.

Food or drink of the present invention preferably has an indication of the purpose, for example to anticyclone”, “for the inhibition of lipid oxidation or for inhibiting the formation of lipid peroxide”. That is, a food product or beverage of the present invention preferably are selling, for example, in the form of food or drink for inhibiting formation of a lipid peroxide, which is an indication of the purpose of use for inhibiting the formation of lipid peroxide and contains a compound selected from a derivative of cyclopentane and derived latinola, as an active ingredient.

“Instruction” includes all instructions that disseminating the comfort of consumers about the purposes described above. That is, “instruction” includes all instructions that can remind you and make you remember any of the above purposes, regardless of the specified objectives, content guidelines and objectives/tools that must be specified.

Further, the phrase “has the indication” means an indication to the notification regarding the purpose of the application of the food product or drink (product).

The specified action preferably is an action that directly notifies consumers about the above purposes. Specific examples include the action (in writing) for the above purposes for the product in accordance with the food product or beverage of the present invention and / or the packaging of this product, advertising for the product and the action (in writing) the above-mentioned goals for a price list or document agreement (including document delivered by electromagnetic means).

Meanwhile, the content of the instructions is preferably the content of the guidelines, which are approved by the government or the like (for example, specify that approved on the basis of data from various institutions established by the government, and has a form-based approval).

Examples of it include instructions for diet food products, functional food product or beverage, disappearing in thin cascapedia product, food for special dietary use, food product with the requirements for dietary, food for special dietary use, food product with the requirements of the functions of nutrients, quatercentenary tool, etc. In particular, the indication includes an indication approved by the Ministry of health, labour and living conditions, such as specifying an approved system of foods for specified health use or a system similar to this system. Examples of the latter include instructions on food for specified health use, indicating the air-conditioned product for specified health use, indication, indicating the possibility of effects on the structure or function of the body and the indication to reduce the risk of disease. Specifically, as a typical instructions are examples of guidance on food for specified health use, marked by decree for a stimulating action in health (the Ordinance No. 86 of Japan Health, Labour and Welfare Ministry, April 30, 2003) (in particular, the indication of a health goal), and guidelines, similar to this order.

Not to mention the fact that the content, showing the above-mentioned purposes, is not limited to expressed enemy to anticyclone”, “for the inhibition of lipid oxidation and to inhibit the formation of lipid peroxide, and the content that includes an expression that shows antioxidative action or effect or inhibitory effect or impact on the formation of lipid peroxide, and the content that includes an expression that refers to the action or effect in relation to preventing the disease or symptom attributed to ROS or lipid peroxide, or action or influence in relation to reducing the risk of disease or symptom, included in the scope of the present invention. Examples include () individual with a higher level of lipid peroxide, individuals with higher levels of lipid peroxide”, “(for) the individual has a problem with the level of lipid peroxide and for the individual having the problem with the level of lipid peroxide”.

In addition, food product or beverage of the present invention preferably includes not only the indication of the above goals, but also the indication of the above-mentioned active ingredient and indication showing the relationship between the objectives and the active ingredient.

Food or drink of the present invention can be manufactured by mixing using as the active ingredient compounds defined is derived from cyclopentane and derived latinola. Food or drink of the present invention can be produced, for example, by mixing the above compounds with the source material of the food product or beverage, and processing the mixture.

In addition, food product or beverage of the present invention can be produced by treatment of the extract, which is obtained by extraction with hot water or various solvents, supercritical extraction or subcritical extraction known plants or similar plants used as source material, which contains the above compound, together with the raw material of the food product or beverage. A specific method of obtaining the extract mentioned in the section “the Drug of the present invention”.

Further, in the case in which the shape of the food product or beverage of the present invention is a granule, tablet or liquid additive, a compound selected from a derivative of cyclopentane and derived latinola, which serves as the active ingredient, preferably made together, for example, sugars such as lactulose, ▫ maltitol and lactic, and other sugars such as dextrin and starch; proteins such as gelatin, soy protein and corn protein; amino acids such as alanine, glutamine and isoleucine; polysaccharides, such as cellulo the a and the Arabian gum; and fats and oils such as soybean oil and triglycerides with a chain of medium length.

The food additive of the present invention

When the antioxidant of the present invention is used in the form of a dietary Supplement (called “food additive of the present invention”), a food additive, which is added to food or drink, can be used to reduce the risk of disease or symptom attributed to oxidation of a biological component, such as a lipid, especially the formation of lipid peroxide, or for the prevention of such disease or symptom.

Further, a food additive of the present invention can be added to food or drink for inhibiting the corrosion of a component in a food product or beverage, such as lipid oxidation, before use. This addition is particularly suitable when the food additive of the present invention is added to food or drink containing fat and oil, or preferably to the food product or beverage containing fat and oil as a main component. Examples of the food or beverage containing fat and oil, are listed in section “a Food product or beverage of the present invention”.

The food additive of the present invention contains a compound selected from the derived cyclo is anusthana and derived latinola, as the active ingredient. The connection can be one or more kinds of compounds.

The food additive of the present invention preferably contains, in combination as a compound selected from a derivative of cyclopentane, and a compound selected from the derived latinola. Each of the derived cyclopentane and derived latinola may be one or more kinds of compounds.

In this case, the mass ratio derived cyclopentane and derived latinola is preferably in the following range: derived cyclopentane:derived latinola= 6,3:2,7-5,1:4,9.

The total concentration of compounds selected from a derivative of cyclopentane and derived latinola in the food additive of the present invention set appropriately. Total concentration is preferably at least 0.001 wt.%, more preferably at least 0.01 wt.%, even more preferably at least 0.05 wt.% or particularly preferably at least 0.1 wt.%. Further, the upper limit of the concentration of the compound in the food additive of the present invention is not specifically limited, for example, the total concentration of 90 wt.% or less, preferably 70 wt.% or less, or more preferably 50 wt.% or less.

Dietary Supplement this is the first invention preferably further comprises an emulsifier. The emulsifier is not specifically limited provided that it can be used in the food product. For example, preferably used emulsifiers that are permitted for use as food additives in Japan, such as the ester of glycerol and fatty acid ester of sucrose and fatty acids, ether sorbitan and fatty acid ester of propylene glycol and fatty acids and lecithins.

When the emulsifier is added to the food additive of the present invention, the dispersibility of the compounds selected from derived cyclopentane and derived latinola serving as an active ingredient, a food additive of the present invention, water-soluble food product or beverage is increased.

The form of a dietary Supplement of the present invention is not specifically limited and a food additive may be in such form, as powder, granule, tablet or liquid, which is usually used in the food additive.

When the food additive of the present invention contains the emulsifier described above, a food additive, in particular, preferably has the shape of an emulsifier. When the additive has the following form, the dispersibility of the compounds selected from derived cyclopentane and derived latinola, water-soluble food product or beverage can be further enhanced.

Food additive nastojasih the invention may contain, in addition to the derived cyclopentane and derived latinola serving as an active ingredient, additive, which is usually used, such as a filler, and an emulsifier. In addition, a food additive of the present invention may contain other known component that is commonly used in the food additive.

The food additive of the present invention can be produced by mixing with the use of compounds selected from a derivative of cyclopentane and derived latinola, as an active ingredient. The food additive of the present invention can be produced, for example, by mixing the above-mentioned active ingredient, preferably with the above-mentioned emulsifier, optionally together with the above additive or other component.

In addition, a food additive of the present invention can be manufactured by mixing the extract, which is obtained by extraction with hot water or various solvents, supercritical extraction or subcritical extraction known plants or similar as a starting material which contains the above compound, preferably together with the above-mentioned emulsifier, optionally together with the above additive or other component. A specific method of obtaining the extract mentioned in the section “Medicine is the main means of the present invention”.

The food additive of the present invention can be applied for manufacturing the above food product or beverage of the present invention. The number of food additives that are added to food or drink, can appropriately be adjusted based on the concentration of the compound selected from the derived cyclopentane and derived latinola and serving as an active ingredient, in the above food product or beverage of the present invention.

Further, a food additive of the present invention preferably has an indication of the purpose, such as to anticyclone”, “for the inhibition of lipid oxidation or for inhibiting the formation of lipid peroxide”.

“Instruction” and “instruction-action” are listed in “Food product or beverage of the present invention”.

Preparation for local application on the skin of the present invention

The antioxidant of the present invention in the form of a preparation for topical application to the skin (called “Preparation for local application on the skin of the present invention”) can be used to treat, or ameliorate, or prevent symptoms of skin disorders attributed to oxidation of a biological component, such as a lipid, in particular the formation of lipid peroxide.

For example, the drug mo is but to apply to reduce or prevent pigmentation, such as spots or freckles, and dermatitis, such as atopic dermatitis or acne, or to reduce or prevent wrinkles, reduce the elasticity of the skin, alopecia and the like.

Preparation for local application to the skin includes everything from drugs, quatercentennial tools and cosmetics.

Preparation for local application on the skin can be made by mixing the compounds represented by compound selected from a derivative of cyclopentane and derived latinola, with a substance, which is usually known. Extraction of such compounds or the like is specified in the section “the Drug of the present invention”.

The method of giving the antioxidant activity of the present invention

The present invention includes a method of making a food product or drink antioxidant activity, preferably activity against inhibition of lipid oxidation, or more preferably activity towards the formation of lipid peroxide, and the method comprises adding a compound selected from the derived cyclopentane and derived latinola to food or drink so that the concentration of the compound in the food or drink was at IU the e 0.0001 wt.%, preferably at least 0.001 wt.%, even more preferably at least 0.005 wt.% or particularly preferably at least 0.01 wt.%. In this case, the definition of “food or drink” is set to a food product or beverage, used above in the section “Food product or beverage of the present invention”.

Further, the ratio of mixing derived cyclopentane and derived latinola or preferred components of these derivatives is the same as used above in the section “Food product or beverage of the present invention”.

The phrase “add connection...” includes the addition compounds obtained by purification or synthesis, as well as the addition of an extract obtained by concentrating the above compounds by extraction with hot water or various solvents, supercritical extraction or subcritical extraction from known plants or similar source, is used as the starting material, which contains the above connection. A specific method of obtaining the extract mentioned in the section “the Drug of the present invention”.

The way to increase the antioxidant activity of the present invention

In addition, the present invention includes a method of increasing the possible antioxidant activity of the food product or beverage, containing a compound selected from a derivative of cyclopentane and derived latinola, preferably inhibitory activity towards the oxidation of lipid, or more preferably inhibitory activity against the formation of lipid peroxide, and the method comprises adding a compound selected from the derived cyclopentane and derived latinola, food product or beverage, so that the total concentration of compounds in the food product or beverage was at least 0.0001 wt.%, preferably at least 0.001 wt.%, even more preferably at least 0.005 wt.% or particularly preferably at least 0.01 wt.%. In this case, the definition of the term “food or drink” also used the value of the food product or beverage specified above in section “a Food product or beverage of the present invention”.

In addition, with regard to the relationship when mixing derived cyclopentane and derived latinola or preferred components of these derivatives, use the relations above in the section “Food product or beverage of the present invention”.

Food or drink containing a compound selected from a derivative of cyclopentane and derived latinola includes a food product or beverage, aderrasi extract of plants of the Liliaceae. Examples include food or drink containing the mesophyll of Aloe. Indicated above, the phrase “add connection ...” includes the addition compounds obtained by purification or synthesis, as well as adding the above extract.

Evaluation of inhibitory effect against the formation of lipid peroxide

Inhibiting action with respect to the formation of lipid peroxide in various samples, comprising the antioxidant of the present invention, can be estimated using as an indicator the number, for example, reactive to thiobarbituric acid (TBA) substances (TBARS). Specifically, we can assume that the greater the amount of TBARS, the greater the amount of lipid peroxide formed.

Examples of TBARS include malonic aldehyde (MDA), which reacts with TBA at high temperatures and acid conditions and is a natural byproduct of perechisleniya lipid. Adduct of MDA-TBA can be detected by measuring the absorption at 530-540 nm for carrying out colorimetric measurement of MDA.

In addition, the inhibitory action against the formation of lipid peroxide test sample can be estimated using APOE-gene-deficient mice, which are often used as model animals who develop arteriosclerosis of the ISU is cholesterolemia (Hyper-LDL-cholesterolemia) (see, for example, reference document 1: "Saibokogaku (Cell Engineering)","Extra Issue", "Medical Experiment Manual" series, Strategy for Study of Arteriosclerosis + Hyperlipidemia, Shujunsha Co., 1st edition, 1st impression, published on April 1, 1996, pp. 441-443).

Model mouse not find obesity, and it is known that they developed Hyper-LDL-cholesterolemia, arteriosclerosis and cardiovascular disease in this order. In addition, in model mice, the level of lipid peroxide is higher than the level in normal mice, and observed the formation of atherosclerotic lesions (plaques) in the arteries. Therefore, the inhibitory effect against the formation of lipid peroxide test sample can be estimated by the introduction of the test sample model mice and measurement of lipid peroxide in blood model mice.

In addition, in General, it is known that the primary damage when arteriosclerosis is called oxidized LDL. Therefore, it is possible to assess the effect in reducing the risk of arteriosclerosis by inhibiting the formation of lipid peroxide test sample by counting the number of atherosclerotic lesions (plaques) in the arteries of each model mice treated with the test sample.

Example obtain 1

(Derivatization of cyclopentane)

To 8.0 g of γ-oryzanol (manufactured by Oryza Oil &Fat Chemical Co., Ltd.) added 250 ml of distilled water, 50 g of sodium hydroxide, 150 ml isop panola, 150 ml of ethanol and 150 ml of methanol and the mixture was heated to boiling under reflux for 2 hours with the use of the heater-casing. After the reaction, the reaction solution was poured into 1300 ml of water and the formed white precipitate was separated by filtration with suction. To flush the residual alkali is separated and the residue is suspended in 1000 ml of water followed by re-filtering with suction. The procedure was repeated twice and the final residue was freeze dried under reduced pressure, thereby obtaining 5,91 g of the hydrolyzate of oryzanol. The hydrolysate was purified HPLC, while receiving 2435 mg of cycloartenol and 1543 mg 24-methylene-9,19-cyclopentan-3-ol.

Then the resulting cycloartenol used for the synthesis of 9,19-cyclopentan-3-ol. 302 mg of cycloartenol, 150 ml of isopropanol and 1.0 g of catalyst, 5% powdered palladium deposited on carbon, were loaded into the autoclave and sealed, followed by replacing the atmosphere of the autoclave with gaseous hydrogen. Then hydrogen gas was introduced under pressure 2930,27 PA (3 kg/cm2). The mixture was heated under stirring and the hydrogen pressure was adjusted to 4883,78 PA (5 kg/cm2when the temperature reached 50°C. the Mixture was allowed to react for 6 hours, while the pressure is maintained by payment of the absorbed hydrogen. The reactions the config solution was filtered to remove the catalyst, concentrated and was purified column chromatography on silica gel (manifesting solvent: 100% chloroform), to thereby obtain 275 mg 9,19-cyclopentan-3-ol.

Example of getting 2

(Derivatization of latinola)

100 kg of mesophyll Aloe barbadensis Miller (clear gel portion) of oriali using homogenizer and to it was added 100 l of solvent mixture (3:1) ethyl acetate/butanol, followed by stirring the mixture. The mixture was stirred over night and were separated by a layer of a solution in a mixture of ethyl acetate/butanol and aqueous layer, followed by the separation layer of a solution in a mixture of ethyl acetate/butanol. A layer of a solution in a mixture of ethyl acetate/butanol was concentrated under reduced pressure, thereby obtaining 13.5 g of extract solution in a mixture of ethyl acetate/butanol.

The solution obtained by dissolving 13 g of the extract in 1 ml of a mixture of chloroform/methanol (1:1)was passed through a column Packed with 400 g of silica gel 60 (manufactured by Merck & Co., Inc.), for adsorption in his column and elution was carried out using the mixture chloroform/methanol (ratio by mixing chloroform:methanol= 100:1, 25:1, 10:1, 5:1 1:1) step gradient method, where the concentration of methanol was increased step by step for fractionation buervenich solutions at a fraction with the corresponding relations used when mixing solvents. Of these coat the s fraction, elyuirovaniya a mixture of chloroform:methanol = 25:1, was subjected to thin-layer chromatography, normal phase and reversed phase (phase manufactured by Merck & Co., Inc., silica gel 60F254 and RP-18F2543) to confirm that the faction was present derived latinola of the present invention.

The solvent of the fraction was removed and the residue was dissolved in a mixture (1:1) chloroform/methanol. The solution was passed through a column Packed with 100 g of silica gel 60 for absorption in his column and elution was carried out using the 1100 ml of a mixture (4:1) hexane/ethyl acetate. Erwerbende fractions were divided into fractions of 300 ml (fraction A), 300 ml (fraction b) and 500 ml (fraction C) in this order.

Thin-layer chromatography, normal phase and reversed phase showed that the derived latinola of the present invention was concentrated in fraction A. Fraction And additionally shared with a mixture of solvents chloroform/hexane (85:15) using HPLC equipped with a COSMOSIL C18 (manufactured by Nacalai Tesque, Inc.), while receiving 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol in the amount of 1.3 mg, 1.2 mg and 1 mg, respectively. The structure of each compound was confirmed by MS and NMR.

Example of getting 3

(The mixture derived cyclopentane and derived latinola)

Peel the leaves of Aloe barbadensis Miller was shot to collect mesophyllous parts and assembled the th mesophyllous part was dried by freezing to produce powder of Aloe vera mesophyll. Then, 806 g of the obtained powder of Aloe vera mesophyll was filed in the camera extraction device supercritical extraction (4 l), manufactured by Mitsubishi Kakoki Kaisha, Ltd., and the extraction was performed for 70 minutes using carbon dioxide extraction conditions: temperature 60°C and a pressure of 30 MPa. From the resulting extract was removed the water, while receiving of 3.85 g of the solid extract.

Identification of components in the resulting solid extract showed that the mass ratio of 9,19-cyclopentan-3-ol, 24-methylene-9,19-cyclopentan-3-ol, 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol was 2,8:3,3:1,4:1,5:1.

Therefore, it was found that the mass ratio of derivatives of cyclopentane and derivatives latinola in a mixture of derivatives of cyclopentane and derivatives latinola received in the sample receiving 3, was as follows: derivatives of cyclopentane:derivatives latinola = 6,1:3,9.

Example 4

(Getting nutritional supplements containing a mixture of derivatives of cyclopentane and derivatives latinola)

Dietary Supplement containing a mixture of derivatives of cyclopentane and derivatives latinola, was obtained by mixing a mixture of derivatives of cyclopentane and derivatives latinola received in the sample receiving 3 (4%), fatty acids with medium chain length (MCT: manufactured by Riken Vitamin Co., Ltd) (2%), ether, glycerin and fatty acids (manufactured by Riken Vitamin Co., Ltd) (4%), saponin (manufactured by Maruzen Pharmaceuticals Co., Ltd.) (0,5%), ethanol (manufactured by Japan Alcohol Corporation) (0,2%), maldita (manufactured by Hayashibara) (1,3%), glycerol (manufactured by NOF CORPORATION) (78%) and water (10%).

EXAMPLES

Further the present invention is described in more detail by means of examples. However, the present invention is not limited to the following examples.

Example 1

Model animals who develop atherosclerosis, ApoE-gene-deficient mice were used to study the inhibitory effect on the formation of lipid peroxide derived cyclopentane, derived latinola and mixtures derived cyclopentane and derived latinola.

(1) Obtaining samples

9,19-Cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol obtained in the above example, obtaining 1, was used as the test sample 1 and test sample 2, respectively.

4-Metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol obtained in the above example get 2, was used as the test sample 3, the test sample 4 and the test sample 5, respectively.

A mixture of derivatives of cyclopentane and derivatives latinola obtained in the above example, the preparation of 3 (derivatives of cyclopentane:derivatives latinola = 6,1:3,9), was used as the test image is 6.

Further, as a control sample was used mevalotin (DAIICHI SANKYO COMPANY, LIMITED.), which is an inhibitor of HMG-CoA reductase inhibitor (a drug for hyperlipemia).

These samples separately dissolved in propylene glycol and diluted with distilled water so as to gain the tested concentrations of each compound 30 μg/ml, and the solutions were used for testing. Should indicate that physiological saline was used as negative control.

(2) Method of test

Six male APOE-gene-deficient mice (purchased from Japan SLC, Inc.) pre-fed food with high cholesterol (manufactured by Research Diets, Inc.) within 2 weeks and were divided into groups of 15 mice in each group.

Mice of each group separately oral introduced the tested solutions, which includes the samples 1-6, a control sample or a negative sample, once a day for 3 consecutive days using health probes in the amount of 1 ml per 25 g of body weight of the mouse. In the early period after the start of administration (14 days after the beginning of the introduction) blood was collected from the tail vein of each mouse and from blood was isolated serum. Then the amount of TBARS was measured using kit OxiSelect TBARS Assay Kit (manufactured MDA Quantitation). Meanwhile, as a control, each norm is Inoi mouse the blood was collected in the same way, as specified above.

(3) the results of the test

The test results of this example are shown in table 1. The table shows the amount of lipid peroxide in blood (concentration of MDA in serum) in the case when the sample was administered to each mouse in the amount of 30 mg per day.

It was found that in the case of mice treated with the negative control, the content of lipid peroxide in blood tended to increase compared with normal mice. However, in the case of model mice, consistently processed test samples 1-6, clearly confirmed the inhibitory effect on the formation of lipid peroxide in blood (there is a significant difference, the symbol “*” in the table). The results show that the introduction of derived cyclopentane, derived latinola or mixture derived cyclopentane and derived latinola APOE-gene-deficient mice leads to decreased concentrations of peroxide lipid in the blood to a level almost equal to the level of peroxide lipid in normal mice, and is effective for prevention or treatment of arteriosclerosis.

On the other hand, in the case of mice treated with the control sample, mevalotin, did not observe a significant reduction in the amount of lipid peroxide in blood compared with the negative sample.

It should be noted that no observed side effects in premawardhana samples and was not an anomaly when establishing pathology after injection.

The above results show that each of the derived cyclopentane, derived latinola or mixture derived cyclopentane and derived latinola has an inhibitory effect on the formation of lipid peroxide and is effective for prevention or treatment of arteriosclerosis.

Table 1
Mouse/sampleThe amount of lipid peroxide in blood (concentration of MDA (μm))The value p
Normal mouse0,5±0,19-
ApoE-gene-deficient mouseThe test sample 10,62±0,010,00000002*
The test sample 20,5±0,190,0001*
The test sample 30,71±0,080,00003*
The test sample 40,69±0,050,000002*
The test sample 5 0,72±0,020,000003*
The test sample 60,69±0,020,000003*
Control sample0,93±0,050,11
Negative sample0,99±0,06-

Example 2

In example 2, each of the derived cyclopentane, derived latinola and mixtures derived cyclopentane and derived latinola evaluated on the action applied to reduce the risk of arteriosclerosis by inhibiting effect on the formation of lipid peroxide by counting the number of atherosclerotic lesions (plaques) in the arteries with the use of known animal models of atherosclerosis, APOE-gene-deficient mice.

(1) get sample

The samples 1-6, control sample and a negative sample was obtained in the same manner as in the above example 1, and each of them was used for testing.

(2) Method of test

Six male APOE-gene-deficient mice (purchased from Japan SLC, Inc.) pre-fed food with high cholesterol (manufactured by Research Diets, Inc.) within 2 weeks and were divided into groups of 15 mice in each group.

Mice each of the groups separately oral was administered to the samples, control sample or a negative sample once a day for 39 consecutive days with medical probes in the amount of 1 ml per 25 g of body weight of the mouse. Forty days after the beginning of the introduction part of the thoracic aorta were fixed with formalin and stained with oil red and counted the number of plaques.

(3) the results of the test

The test results of this example are shown in table 2. The table shows the number of atherosclerotic lesions (plaques) in the arteries model mice treated with solutions of samples.

The results showed that the number of plaques model mice treated with the negative control, as found, was 12,2, while discovered that the number of plaques model mice treated with test samples 1-6 were halved to 5.0-6.2, and each of the test samples had inhibitory effect on plaque formation on the arterial endothelium.

On the other hand, in the case of mice treated with the control sample, mevalotin, which is a drug for hyperlipidemia, no significant differences, although it was found that the formation of plaques decreased compared with the negative sample.

It should be noted that during the administration of the test samples were not observed side effects and was not an anomaly when the study is assured of pathological changes in mice after injection.

The above results showed that each of the derived cyclopentane, derived latinola and mixtures derived cyclopentane and derived latinola has an inhibitory effect on plaque formation in Vienna and reduces the risk of arteriosclerosis by inhibiting effect on the formation of lipid peroxide.

Table 2
Mouse/sampleThe number of plaques formed in the thoracic aortaThe value p
ApoE-gene-deficient mouseThe test sample 16,0±0,70,009*
The test sample 25,6±1,50,0006*
The test sample 36,2±1,90,008*
The test sample 45,0±1,40,003*
The test sample 55,6±2,10,005*
The test sample 6 5,4±2,00,004*
Control sample10,6±3,20,25
Negative sample12,2±3,0-

Industrial applicability

The antioxidant of the present invention can be safely enter and this antioxidant inhibits the oxidation of a biological component, in particular inhibits the formation of lipid peroxide in blood. Therefore, the antioxidant is effective for the treatment and/or prevention of diseases and symptoms, such as arteriosclerosis, cerebral hemorrhage, angina pectoris, myocardial infarction, liver dysfunction, cirrhosis, hepatitis, retinopathy, cataract, Alzheimer's disease, Parkinson's disease, allergic disease, cancer, roughness and skin aging. The antioxidant of the present invention has excellent effects in the treatment and/or prevention of arteriosclerosis, angina and myocardial infarction. Accordingly, the drug of the present invention is applicable for treating or preventing the above diseases and symptoms. In addition, food product or beverage of the present invention is applicable is output when used to prevent the above disease States and symptoms and to reduce the risk of their occurrence, since the food or drink can be consumed safely and effectively inhibits the formation of lipid peroxide in vivo, in particular in the blood. In addition, a food additive of the present invention is applicable to the manufacture of such food or beverage and inhibiting oxidation of a component in a food product or beverage. In addition, the preparation for topical application to the skin of the present invention is applicable to treat or ameliorate symptoms or prevent pigmentation, such as spots or freckles, dermatitis, such as atopic dermatitis or acne, or for smoothing or prevent wrinkles, cure or ameliorate symptoms of decreasing elasticity of the skin, alopecia and the like.

1. Drug for inhibiting the formation of lipid peroxide-containing compound selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol in a concentration of at least of 0.0001 wt.% as the active ingredient.

2. The drug according to claim 1, containing a derivative of cyclopentane and derived latinola at the following mass ratio derived cyclo is anusthana: derived latinola=6,3:2,7-5,1:4,9.

3. The method of manufacture of a medicinal product according to claim 1 or 2, comprising mixing compounds selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol as an active ingredient.

4. Food or drink for inhibiting the formation of lipid peroxide-containing compound selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol in a concentration of at least of 0.0001 wt.% as the active ingredient.

5. Food or drink according to claim 4, containing a derivative of cyclopentane and derived latinola at the following mass ratio derived cyclopentane: derived latinola=6,3:2,7-5,1:4,9.

6. Food or drink according to claim 4, further containing an emulsifier.

7. Food or drink according to claim 4, containing fat and oil.

8. Food or drink according to claim 4, which is a functional food product or beverage.

9. A method of manufacturing a food or beverage according to any one of claims 4 to 8, comprising mixing is soedineniya, selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol as an active ingredient.

10. Food additive for inhibiting the formation of lipid peroxide-containing compound selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol in a concentration of at least of 0.0001 wt.% as the active ingredient.

11. Dietary Supplement of claim 10, further containing an emulsifier.

12. Dietary Supplement of claim 10, containing a derivative of cyclopentane and derived latinola at the following mass ratio derived cyclopentane: derived latinola=6,3:2,7-5,1:4,9.

13. A method of manufacturing a food additive according to any one of p-12, comprising mixing compounds selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol as an active ingredient.

14. The use of the compounds defined is derived from cyclopentane, selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol for the manufacture of an antioxidant, where the antioxidant contains a compound selected from a derivative of cyclopentane and derived latinola at a concentration of at least of 0.0001 wt.%.

15. The use of a composition containing a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol in the following mass balance for the production of antioxidant: derived cyclopentane: derived latinola=6,3:2,7-5,1:4,9, where the antioxidant comprises a derivative selected from the derived cyclopentane and derived latinola at a concentration of at least of 0.0001 wt.%.

16. The method of giving the antioxidant activity of the food product or beverage, comprising adding a compound selected from the derived cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol, to the food product or drink so that the total concentration of compounds in the diet is the first food or beverage was at least of 0.0001 wt.%.

17. The way to increase the antioxidant activity of food or drink containing a compound selected from a derivative of cyclopentane and derived latinola containing the addition of compounds selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol, food product or beverage, the total concentration of compounds in the food product or beverage was at least of 0.0001 wt.%.

18. A method of treating or preventing the disease or symptom attributed to oxidation, including the introduction of compounds selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol, at a concentration of at least of 0.0001 wt.% the entity that needs anticyclone.

19. A method of treating or preventing the disease or symptom attributed to oxidation, p, including the introduction of derived cyclopentane and derived latinola at the following mass ratio derived cyclopentane: derived latinola=6,3:2,7-5,1:4,9.

20. The method of treatment or is recuperate disease or symptom, attributed to oxidation, including the introduction of a composition containing a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol in a concentration of at least of 0.0001 wt.% when the next mass ratio derived cyclopentane: derived latinola=6,3:2,7-5,1:4,9, to a subject who needs anticyclone.

21. Antioxidant-containing compound selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol, at a concentration of at least of 0.0001 wt.% as the active ingredient.

22. The antioxidant according to item 21, containing a derivative of cyclopentane and derived latinola at the following mass ratio derived cyclopentane: derived latinola=6,3:2,7-5,1:4,9.

23. The antioxidant according to item 21 for inhibiting lipid oxidation.

24. The antioxidant according to item 23 for inhibiting formation of a lipid peroxide.

25. The antioxidant according to item 21, which is a preparation for topical application to the skin.

26. The antioxidant according to item 21,which is made in the form of food or drink.

27. Ant the oxidant on p, in which food or drink contains an emulsifier.

28. The method of manufacture of an antioxidant according to any one of p-27 containing the mixing of compounds selected from a derivative of cyclopentane selected from 9,19-cyclopentan-3-ol and 24-methylene-9,19-cyclopentan-3-ol, and derived latinola selected from 4-metalholic-7-EN-3-ol, 4-metalurgist-7-EN-3-ol and 4-methylstyryl-7-EN-3-ol as an active ingredient.



 

Same patents:

Antiviral compouds // 2441869

FIELD: pharmacology.

SUBSTANCE: invention refers to the new compounds or its pharmaceutically acceptable salts where the compound has formula I possessing the activity towards hepatitis C virus (HCV). In the compound of formula I, Each W1 and W2 means nitrogen, W3 is chosen out of group consisting of nitrogen and -CH-, and W4 is -CH-; A is phenyl and is not mandatory substituted, X is chosen out of group consisting out of bond, -O- and -S-, Z is chosen out of group consisting of -CH2- and -NH-; R22 is chosen out of group consisting of hydrogen, benzimidazole, indole and thiophene, where R22 is not mandatory substituted, Y is chosen out of group consisting of C(O)N(R15)- and -N(R15)C(O)-, where R15 in each case is chosen out of group consisting of hydrogen and C1-C6alkyl; R50 is -L1-A1 where L1 is chosen out of group consisting of bond and C1-C6alkylene, and A1 is chosen out of group consisting of phenyl, pyridyl, benzothiazolyl, thiadiazole, isothiazole and thiophene, where A1 is not mandatory replaced, each R10 and R35 means hydrogen; R17 is C1-C6alkyl; and each C3-C18carbocyclil and M3-M18heterocyclil in -LE-Q-LE-(C3-C18carbocyclil) and -LE-Q-LE-( M3-M18heterocyclil) is not mandatory independently substituted in each case.

EFFECT: enhanced cure of hepatitis C.

13 cl, 12 dwg, 459 ex

FIELD: chemistry.

SUBSTANCE: described is a method of producing 7,8-dihydro-analogues of ecdysteroids via catalytic hydrogenation of ecdysteroids in methanol solution containing 1:6-fold excess Na metal in the presence of a Pd/C catalyst (1:1 to the weight of the substrate).

EFFECT: obtained 7,8-dihydro-analogues of ecdysteroids are structurally similar to castasterone type brassinosteroids - highly active phytohormones, plant growth and development stimulants.

3 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described is sugar-cholestanol compound, which can be easily synthesized, and which demonstrates sufficient anti-tumour activity.

EFFECT: claimed is anti-tumour medication, which as active ingredient, contains cholestanol compound, represented by the following formula (1) or cyclodextrin complex of inclusion, which contains said compound.

6 cl, 2 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to chemistry of natural compounds, specifically to enhanced synthesis of ecdysteroids - insect molting hormones. The invention describes a single-step method for synthesis of 2-dehydro-3-epi-20-hydroxyecdysone 1 during ozonation of 20-hydroxyecdysone (2) in a pyridine solution at 0-25°C for 10-20 minutes. Ecdysteroid 1 obtained that way was extracted in crystalline form with output of 83% in terms of reacted 20-hydroxyecdysone (2). Melting point and specific angle of rotation were further determined for the 20-hydroxyecdysone. The structure of the obtained product was confirmed through a combination of 1D and 2D NMR 1H and 13C spectra.

EFFECT: method ensures high output of ecdysteroid via a single-step process.

1 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention is related to cholesterol-6-O-acyl-β-D-galactopyranoside intended for inducing in a host mammal of immune reaction on B.burgdorferi, where (i) residual acyl represents a group recovered from organic fatty acids containing 1-25 carbon atoms; (ii) galactopyranoside ring structure optionally contains acyl group recovered from fatty acid in any position of the ring. The invention also covers mixed 3-O-(6-O-palmitoyl-(β-D-galactopyranosyl)-cholesterol and 3-O-(6-O-oleoyl-β-D-galactopyranosyl)cholesterol intended for inducing in a host mammal of immune reaction on B.Burgdorferi.

EFFECT: compounds are especially effective for prevention or treatment of Lim's disease.

7 cl, 4 tbl, 15 dwg, 15 ex

FIELD: medicine.

SUBSTANCE: there is described pharmaceutical preparation or beverage/foodstuff which can inhibit production of adipocytokine, in particular adipocytokine which can induce insulin resistance. The pharmaceutical preparation or beverage/foodstuff contains as an active component a compound chosen from the group consisting of 4-methylcholest-7-ene-3-ole, 4-methylergost-7-ene-3-ole and 4-methylstigmast-7-ene-3-ole or a herbal extract of Liliaceae family, an organic solvent or hot water, containing at least 0.001 wt % of the compound.

EFFECT: prevention or simplification of the disease cases associated with insulin resistance.

7 cl, 4 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: present invention presents a preparation to reduce insulin resistance. The preparation contains 3-O-v-D-glucopyranosyl-4-methylergost-7-ene-3-ole, or an extract made with using an organic solvent, or an extract made with using hot water, or a drained liquid of a plant of Liliaceae family, or fraction thereof which contains this compound as an active component.

EFFECT: production of the preparation which is suitable for inhibition of adipocytokine production, particularly adipocytokine which cause insulin resistance, and for prevention of pathological conditions caused by insulin resistance, or simplification of clinical course of said pathological conditions.

9 cl, 3 ex

FIELD: production processes.

SUBSTANCE: invention refers to wood working and wood chemical industries. Birch bark is broken down, mixed with liquid, the mixture is held at temperature higher than mixture freezing temperature, then triterpene compounds are separated from lingo-adipic residue with the following filtration and drying. Birch bark is additionally broken down by method of impact-abrasing and/or abrasing effect till obtaining birch bark flour. Birch bark flour is mixed with liquid with density of 0.999-0.958 kg/m3. Mixture is held for 0.1-10 hours and then separated by flotation to hydrophobic and hydrophilous fraction. Solution remaining after separation is condensed and dried. Obtained hydrophobic fraction - mixture of triterpene compounds - is exposed to recrystallisation in ethanol with activated charcoal and then betuline, solution of triterpene compounds in ethanol and mixture of triterpene and polyphenol compounds at carbon matrix is obtained. Or triterpene compounds mixture is separated to fractions in carbon-dioxide extractor and betuline, dry mixture of triterpene and polyphenol compounds are obtained. Hydrophilous fraction - lingo-adipic flour - is separated from liquid and dried out.

EFFECT: increase of environmental safety and method effectiveness.

6 cl, 4 ex, 3 dwg

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel fusidic acid derivatives of general formula [I], where X represents halogen, trifluoromethyl, C1-C7alkyl, substituted with phenyl, C2-C9alkenyl, optionally substituted with C1-C7alkyl, halogen or phenyl, phenyl, optionally substituted with one or two similar or different substituents, selected from group consisting of halogen, C1-C7alkyl, C2-C9alkenyl, phenyl, C1-C6alkoxy, nitro, C1-C6alkyltio, trifluoromethyl and cyano; or X represents naphtyl; Y and Z both represent hydrogen or together with bond C-17/C-20 form double bond between C-17 and C-20 or together represent methylene and form cyclopropane ring in combination with C-17 and C-20; A represents O, S or S(O); B represents C1-6alkyl, C2-6alkenyl, C1-6acyl, phenyl or benzoyl, where C1-6alkyl is optionally substituted with one or more halogens, hydroxy, C2-6alkenyl, phenyl, C1-4heteroaryl or C1-6alkoxy; Q1 represents -(CHOH)-, or -(CHW)-, where W represents halogen or azido; Q2 represents -(CHOH)-; to their pharmaceutically acceptable salts and easily hydrolysed esters and to pharmaceutical compositions, including said derivatives, as well as to their application in therapy.

EFFECT: application in therapy.

31 cl, 127 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to synthesis of biologically active substances, in particular specifically, to improved method of producing 2,3-monoacetonide 20-hydroxyecdysone of formula found in very small amounts in some plants, e.g. Rhaponticum carthamoides. Method is implemented by interaction of 20- hydroxyecdysone (1.0 g, 2.08 mmole) and acetone with phosphomolybdic acid (PMA) added. As suspension is effected by mother compound in PMA acetone (0.3 g, 0.16 mmole), after 5 min homogenisation of reaction mixture is observed to be steamed by neutralisation with 0.1% sodium hydrocarbonate solution with following ethyl acetate and chromatography extraction of the end product, thus resulting in isolation of the end 2,3-monoacetonide 20- hydroxyecdysone of 32% yield.

EFFECT: method is highly selective and single-stage.

2 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 , where X and T are N or C, Q is a (3-7)-member aromatic ring which contains 0-3 nitrogen atoms as ring members, and which is optionally benzo-condensed and is substituted with oxo; C1-C6-alkyl; halogen- C1-C6-alkyl; hydroxy-C1-C6-alkyl; C1-C6-alkoxy; C6-C10-aryl; or a (3-7)-member heteroaryl containing 1-3 oxygen atoms, P is C1-C6-alkyl, optionally substituted with a halogen, and R is a group selected from: (i) -C1-C6-alkyl-R1, (ii) -NR2R3, (iii) -O-R4, (iv) -S-R5, (v) -C (=O))-R6, (vi) optionally substituted (3-7)-member heteroaryl containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vi) optionally substituted (3-7)-member heteroatom containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vii) optionally substituted, saturated or partially unsaturated, separate or condensed (3-10)-member heterocyclic ring containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (viii) azido; where each R1, R2, R3, R4, R3, R6, is as described in the claim. The invention also relates to a pharmaceutical composition for preventing and treating a vascular disease, which contains a compound of formula 1.

EFFECT: compounds of formula 1 with inhibitory activity with reference to aggregation of thrombocytes.

7 cl, 7 dwg, 2 tbl, 519 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to an oral solid dosage form containing a therapeutically effective amount of aliskiren or its pharmaceutically acceptable salt wherein an active ingredient makes more than 46 wt % of total weight of the oral dosage form. The oral dosage form is presented in the form of a tablet or a film-coated tablet, and contains an internal phase containting aliskiren or its pharmaceutically acceptable salt, an excipient, a binding agent and a disintegrant, and an external phase containing a disintegrant, an excipient, a glidant and a lubricant.

EFFECT: invention provides administration of the active ingredient aliskiren in the small oral dosage form; it is characterised by an acceptable disintegration time.

32 cl, 2 ex

FIELD: medicine.

SUBSTANCE: correction of ischemic disorders caused by reperfusion liver injury in experiment in white Wistar male rats involves modelling an ischemic and reperfusion liver injury. 30 Minutes before, L-norvalin arginase blocker 10 mg/kg is introduced intraperitoneally, and distant ischemic pre-conditioning is conducted. Then, another dose of L-norvalin arginase blocker is introduced immediately after liver ischemia.

EFFECT: effective correction of the hepatocellular damage ensured by minimising the oxidative stress effects.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns methods of treating acute cerebrovascular disease. A method of treating acute ischemic and hemorrhagic cerebrovascular disease consists in administering a pharmaceutical composition containing a protein-polypeptide complex taken as a biologically active substance and prepared of fast-frozen embryo brain of hoofed farm animals of a gestation term from the middle of the first one-third to the middle of the last one-third of pregnancy, in the amount of 0.05-0.8 mg/day subcutaneously, intramuscularly, intravenously, intranasally and intrathecally. Said protein-polypeptide complex contains negative weak acid neutral proteins and polypeptides referring to growth/differentiation factors, signal molecules, intercellular adhesion molecule, of molecular weights 5 to 200 kD with min. 80% of total weight of proteins having molecular weight 10 to 120 kDa, and characterised nu a peak at UV wave length 274-284 nm and bands at the pi values of 4.2 to 8.4 at isoelectric focusing in 5% polyacrylamide gel.

EFFECT: protein-peptide complex is safe and tolerable when in use; it is effective in treating the patients with acute cerebrovascular disease that ensures clinically significant effect of survivability, dynamics and recovery length of the lost functions in the patients when using the method.

4 cl, 9 tbl, 23 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to using a compound of formula (I):

wherein R represents a hydrogen atom or CH3, and X represents a physiologically acceptable counter ion for preparing a hepatoprotective agent for treating or preventing a liver injury. The invention also refers to a method for treating or preventing the liver injury which involves a therapeutically or preventive effective amount of said compound of formula (I).

EFFECT: declared group of inventions provides hepatoprotective activity ensured by an ability of the compounds of formula (I) to improve an endothelium function to release endogenic prostacyclin.

14 cl, 7 dwg, 3 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely anaesthesiology, and concerns the early postoperative drug-induced correction of central hemodynamic disorders in oncological patients. That is ensured by measuring a cardiac index (CI), an impact index (II), a LV filling pressure (LVFP), a total peripheral vascular resistance (TPVR), a LV mechanical work index (LVMWI), a systolic blood pressure (SBP); the derived relations of these values in a patient are used to prescribe an individual drug-induced therapy.

EFFECT: method provides reducing a number of hemodynamic complication in this group of patients by taking account of the individual haemodynamic values of the particular patient.

5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly a drug preparation for preventing the development of cardiovascular diseases in individuals of a high-risk group. A capsule for preventing the development of cardiovascular diseases in individuals of a high-risk group which contains acetylsalicylic acid tablets coated by partially hydrolised polyvinyl alcohol (PVA), tablets of simvastatin and pravastatin coated by hydroxypropyl methylcellulose (HPMC) and tablets of lisinopril, ramipril or perindopril coated by partially hydrolised polyvinyl chloride. Using the capsule in producing the drug preparation for preventing the development of cardiovascular diseases in individuals of a high-risk group.

EFFECT: capsule is stable at variable temperature and relative humidity, as well as resistant to decomposition of the active ingredients under exposure to light.

8 cl, 29 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel tetrahydroisoquinoline derivatives of general formula (I) or pharmacologically acceptable salts thereof, where R1 is a phenyl aminocarbonyl group which can be substituted with 1-3 groups independently selected from a substituting group A, a heteroaryl aminocarbonyl group, where the heteroaryl is pyridine, pyrazine, thiazole, pyrazole or isoxazole, which can be substituted with 1 group selected from a substituting group A, benzoxazol-2-yl group, which can be substituted with 1 group selected from a substituting group A, benzothiazol-2-yl group, (C1-C6 alkyl which can be monosubstituted with a C3-C6 cycloalkyl group), aminocarbonyl group, (C3-C6 cycloalkyl)aminocarbonyl group or adamantyl aminocarbonyl group; R2 independently represents a C1-C6 alkyl group; R3 is a heterocyclic group, where the heterocycle is oxazole, oxadiazole, pyrazole, isoxazole or tetrazole, which can be substituted with 1 group selected from a substituting group A, a group of formula -C(=O)-O-R4, or a group of formula -C(=O)-N(R5)R6; R4 is a hydrogen atom, a C1-C6 alkyl group which can be substituted with 1-2 groups independently selected from a substituting group B; R5 is a hydrogen atom, a C1-C6 alkyl group which can be substituted with 1 group selected from a substituting group B, a C3-C6 cycloalkyl group which is monosubstituted with a carboxyl group, or a heterocyclic group, where the heterocycle is tetrazole, which can be substituted with 1 group selected from a substituting group A; R6 is a hydrogen atom or a C1-C6 alkyl group; in those cases when both R5 and R6 represent a C1-C6 alkyl group, which can be substituted with 1 group selected from a substituting group B, their carbon atoms can be bonded to each other to form a 5-member saturated ring; X is an oxygen atom, a methylene group, a group of formula -NH-, a methylene group which is monosubstituted with a C1-C6 alkyl group, or a group of formula -N(R7)-; R7 is a C1-C6 alkyl group; L is a single bond, a methylene group, a 1,1-dimethylmethylene group, an ethylene group, a group of formula - CH=, or a methylene group which is monosubstituted with a C1-C6 alkyl group; … denotes a single bond or a double bond (however, … denotes a single bond when L is a group of formula -CH=); m equals 1 or 2; n equals 0 or 1; substituting group A is a group of substitutes selected from a halogen atom, a C1-C6 alkyl group, a C1-C6 halogenated alkyl group, a C1-C6 alkoxy group, a C1-C6 halogenated alkoxy group, a C1-C6 alkylthio group, a carboxyl group, a di-(C1-C6 alkyl)amino group, a cyano group, a hydroxy group, a C1-C6 alkylthionyl group and an oxo group; and substituting group B is a group of substitutes selected from a carboxyl group and a hydroxy group. The invention also relates to a pharmaceutical composition based on the compound of formula (I), use of the compound of formula (I) and a method of treating and/or preventing a disease.

EFFECT: obtaining novel tetrahydroisoquinoline derivatives, having excellent inhibiting action on acyl-coenzyme A: diacylglycerol-acyltransferase and excellent food intake suppression.

31 cl, 113 ex

FIELD: chemistry.

SUBSTANCE: disclosed are novel 4-dimethyl aminobutyric acid derivatives of formula (I) (pharmaceutically acceptable salts thereof), where values of A1, A2, R1, m and n are given in the claim, which inhibit activity of carnitine palmitoyltransferase (CPT), and more specifically CPT2.

EFFECT: compounds are an agent of pharmaceutical compositions, having CPT2 inhibiting activity.

18 cl, 71 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (IX) wherein radicals and symbols have values given in the claim, and pharmaceutically acceptable salts or tautomers thereof. Said compounds are inhibitors of poly(ADP-ribose)polymerase (PARP) and can be used to treat cancer, inflammatory diseases, reperfusion injuries, ischaemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, retroviral infections, retinal damage, skin senescence and UV-induced skin damage, and as chemo- or radiosensitisers for cancer treatment. The invention also relates to a pharmaceutical composition containing said compounds, use of said compounds and a method of treating said diseases.

EFFECT: high efficiency of using the compounds.

10 cl, 18 ex

FIELD: medicine.

SUBSTANCE: invention refers to a formulation of (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide possessing modulatory activity with an adequate effect, to a pharmaceutical substance of (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide containing: 2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide - min. 99.0% and max. 100.5% at a dry substance; individual accompanying impurities, either single or total - max. 0.2%; the residual quantities of organic solvents, either single or total - max. 3000 ppm. The invention also refers to a method for preparing a pharmaceutical substance differing by the fact that the raw material is purified, crystallised, stabilised by treating the formulation in demineralised water that is followed by isothermal crystallisation from propanol, and drying. The invention also refers to compositions for internal and external application.

EFFECT: invention provides higher efficacy, safety, stability and width of therapeutic application.

55 cl, 3 dwg, 80 tbl, 27 ex

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