WO2006090910A1 - Nouveau glycoside steroidien, substance active associée au ngf, procede pour les produire, procede de depstage de ceux-ci et agent de prevention d’un dysfonctionnement cerebral - Google Patents

Nouveau glycoside steroidien, substance active associée au ngf, procede pour les produire, procede de depstage de ceux-ci et agent de prevention d’un dysfonctionnement cerebral Download PDF

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Publication number
WO2006090910A1
WO2006090910A1 PCT/JP2006/304036 JP2006304036W WO2006090910A1 WO 2006090910 A1 WO2006090910 A1 WO 2006090910A1 JP 2006304036 W JP2006304036 W JP 2006304036W WO 2006090910 A1 WO2006090910 A1 WO 2006090910A1
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Prior art keywords
ngf
active substance
nucleus
related active
formula
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PCT/JP2006/304036
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English (en)
Japanese (ja)
Inventor
Makoto Ojika
Jianhua Qi
Youji Sakagami
Takayoshi Mamiya
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National University Corporation Nagoya University
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Priority to JP2007504844A priority Critical patent/JP5092122B2/ja
Publication of WO2006090910A1 publication Critical patent/WO2006090910A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/90—Plate chromatography, e.g. thin layer or paper chromatography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Definitions

  • the present invention relates to novel steroidal glycosides and NGF-related active substances isolated from honhi tode (scientific name: Acanthaster planci) etc.
  • the present invention relates to a method of producing and searching a coactive substance.
  • starfish honithde
  • the sea urchin starfish leaves the stomach through the mouth in the middle of the lower part of the body, secrets digestive fluid and eats living coral.
  • dipers etc. will be stabbed with a beard and are therefore targeted for extermination. Disclosure of the invention
  • the present inventors are studying the identification and utilization of components contained in starfish through the research of marine organisms such as the starfish.
  • a novel teroid glycoside contained in the starfish has neurite outgrowth activity ( It has been reported that it has a "neural growth factor (NGF) -like activity" (J. Qi et al, Bioorganic & Medicinal Chemistry (2004), 12 (15), 4259-4265.).
  • NGF neural growth factor
  • the present invention has been made in view of the above-mentioned circumstances, and provides an effective utilization method which is clarified by the study of novel steroid glycosides and novel steroid glycosides which have been made clear through the study of von starfish. Means to solve the problem
  • NGF enhancing activity NGF-like activity and NGF enhancing activity are combined to Associated with NGF-related activity
  • steroid is a general term for compounds having a penolehydrocyclopentaphenanthrene ring, but in the present specification, part or all of hydrogen constituting the perhydrocyclopentaphenanthrene ring is removed.
  • those having a skeleton in which a carbon-carbon double bond is formed are also described as steroids.
  • compounds in which the bond between the carbons at positions 4 and 5 of the perhydrodicyclic pentafucanthrene ring is a double bond are specifically described.
  • the novel steroidal glycoside of the present invention is a compound having a structure shown in the following general formula (1) or formula 39A.
  • X is X 1 or X 2; any one of the Y is one of Y 1 and Y 3 when X is X 1, when X is X 2 ⁇ 1 ⁇ 3
  • ⁇ 1 to 2 and ⁇ 1 to 3 are substituents bonded at a part of *.
  • novel steroidal glycosides of the present invention can be represented by the following general formula (1 ′) or (1 ′ ′), or by the formula 64-3, 65-3, 69-11 or 101-3 It is a steroid glycoside represented.
  • Y is any one of Y 4 to 7.
  • R is hydrogen if ⁇ is ⁇ 4 and methyl if ⁇ 5 to 7 .
  • 4 to 7 each represents a substituent bonded to a part of *.
  • Y is Y 4 '6 ⁇ is any one of the 8.
  • R is When Y is Y 4 in the case of hydrogen, Y 5 ⁇ 7 is a methyl group. Note , ⁇ 4 , 6 to 8 combine in the part of *
  • the compounds shown in (a) and (b) are compounds which have not been conventionally isolated from von starfish and have a structure in which one monosaccharide is bonded to one end or both ends of the steroid skeleton. .
  • steroid glycosides contained in starfish are known to have strong toxicity, but these compounds show strong NGF-like activity and pino or NGF enhancing activity below the concentration at which toxicity appears. .
  • the steroid glycosides represented by the general formulas (1), (1 ′) and (1 ′ ′) and the formulas 39A, 64-3, 65-3, 69-1 and 10-13 have NGF-related activity
  • the “substance” such as “NGF-related active substance” or the like may be a pure compound or a mixture containing a plurality of compounds.
  • the general formula (1) it can be sufficiently predicted that compounds in which X is X 1 and Y is Y 2 also have NGF related activity (at least NGF enhancing activity).
  • the general formula (1 Among ') and (1 ") regardless of the kind of Y, it can be sufficiently predicted that compounds freely selected from hydrogen and methyl group also have NGF related activity (at least NGF enhancing activity).
  • the NGF-related active substance of the present invention has a tetracyclic fused nucleus described in the following formula (2) as a skeleton, and one or two monosaccharides are directly or indirectly bound to each of a nucleus and a nucleus. And a steroid glycoside.
  • each nucleus of A to D may have a double bond, and any hydrogen atom may be substituted by one OR group (R is hydrogen, an alkyl group or a group) or a methyl group. can do. )
  • a monosaccharide directly binds to the A nucleus (D nucleus) means that one or two monosaccharides (in the case of two disaccharides including monosaccharides bound by monosaccharides) are OH in the monosaccharides. It means that it is bound to A nucleus etc. by group.
  • a monosaccharide is indirectly linked to A nucleus (D nucleus) means that one or two monosaccharides (in the case of two, including a disaccharide linked by monosaccharides) are at least one It means that it is bound to A nucleus etc. by OH group in the monosaccharide via the group consisting of carbon atom etc.
  • the group to be interposed may have a ketone, an ether, a double bond and the like in part or all in addition to the vanolexylene group.
  • a compound in which one monosaccharide is bound to each of the A nucleus and the D nucleus exhibits an NGF-like activity and an NGF enhancing activity
  • one or two of the A nucleus and the D nucleus are one or two.
  • compounds to which a monosaccharide is bound mainly exhibit NGF enhancing activity. Therefore, as a steroid glycoside having NGF enhancing activity, a compound in which one or two monosaccharides are directly or indirectly bound to either one of the A nucleus and the D nucleus. is there.
  • At least one of the following formulas 33B, 34B2, 39A2, 39A3, 74-2 and 74-4 can be exemplified as the above-mentioned steroid glycosides mainly exhibiting NGF enhancing activity. All of these compounds are known compounds isolated from starfish other than starfish, but this time they have been clarified by the present inventors to have NGF related activity.
  • the steroid glycoside can be a compound contained in an extract from an organism belonging to the starfish class.
  • a step of separating a fraction from the hydrophobic fraction by a K-well chromatograph method can be employed. By separating the fractions exhibiting this R f value, it is possible to obtain NGF related active substances showing high NGF related activity.
  • the highly toxic fraction can be removed by excluding the fraction showing this R f value.
  • the step of separating by the chromatography method it is possible to obtain an NGF related active substance exhibiting higher NGF related activity by including the step of separating the fraction having the R f value of 0.52 or more. it can.
  • the step of separating by the chromatography method can also include the step of separating a fraction having an R f value of 0.39 or less.
  • the NGF-related active substance obtained by these production methods preferably contains at least one compound in the group consisting of the above-mentioned novel steroid glycosides.
  • the method for searching for an NGF-related active substance of the present invention is characterized in that the tetracyclic condensation nucleus described in the above-mentioned formula (2) is a skeleton, and at least one of A nucleus and D nucleus directly or 1 monosaccharide It is important to determine the presence or absence of NGF-related activity by whether or not it contains a steroid glycoside that is indirectly linked.
  • the compound in which the tetracyclic fused nucleus represented by the formula (2) is bonded to a monosaccharide is a compound which is easy to determine whether it contains or not, as represented by saponin and the like. Then, the position and number of bonds of the monosaccharide are determined to determine whether or not the compound corresponds to a compound in which the tetracyclic condensation nucleus represented by the above-mentioned formula (2) is bonded to a predetermined monosaccharide. Good.
  • the method is a simple method as a whole, as compared with the conventional methods for screening a wide variety of GF-related active substances.
  • glycosides such as steroid glycosides
  • the relatively easy operation of detecting glycosides (such as steroid glycosides) in which a sugar is bonded to a 4-ring condensed nucleus is a promising possibility that it may become an NGF-related active substance and its source animal (plant).
  • the candidates can be narrowed down roughly, and the time required for the search can be greatly reduced.
  • NGF-related active substances can be searched.
  • NGF-related active substances are searched without performing PC12-cell assay by determining whether the structure of the many steroid glycosides that have been discovered so far has the above-mentioned structure or not. can do.
  • the steroid glycoside is searched from an extract from a starfish class.
  • the NGF-related active substance of the present invention has an unprecedented high activity. And, since it can be easily separated from ornithite which is required to be eliminated, it can also be a motivation for the elimination of ornithodete beyond its excellent availability.
  • the method for searching for an NGF-related active substance of the present invention has an effect of being able to easily search for an NGF-related active substance other than searching for an active ingredient in a natural resource.
  • Fig. 1 Analysis of the active fraction fr. A obtained from the extract of the sea urchin starfish obtained in the example by HPLC (1st round) and a diagram showing the steroid glycoside corresponding to each peak It is.
  • Fig. 2 is a copy of a photomicrograph showing the appearance of adding Acanthasteroside 40 A and NGF to PC12 cells.
  • FIG. 3 The results of analysis of the active fraction fr. C obtained from the extract of honichdee obtained in the example with H PLC (1st round) and the corresponding steroid glycosides are shown.
  • FIG. 3 The results of analysis of the active fraction fr. C obtained from the extract of honichdee obtained in the example with H PLC (1st round) and the corresponding steroid glycosides are shown.
  • FIG. 4 is a graph showing the evaluation results of the effect on learning memory impairment in aged male mice of the Example. BEST MODE FOR CARRYING OUT THE INVENTION
  • novel steroidal glycosides of the present invention are six compounds of acanthasterosides 34 A, 34 B, 34 C, 39 A, 4 OA and 4 OB shown below, and a compound of the following formula 80-3: , 92-2, 78-3, 101-3, 64-3, 65-2, 65-3, 76-3, 62-3, 69-1 1, 42-2 (acanth terror side 39 B), 35 12 compounds of -2 (acanthasteroside 39 A4).
  • the NGF-related active substances of the present invention include the above-mentioned novel steroid glycosides.
  • each nucleus of A to D can independently have a double bond.
  • any hydrogen atom can be substituted with one OR group (R is hydrogen, an alkyl group or an asyl group) or a methyl group.
  • the alkyl group is preferably from about 3 to 3 carbon atoms, particularly preferably a methylole group, and the acyl group is preferably from about 1 to 3 carbon atoms, and more preferably an acetyl group. It is also desirable not to have a tetracyclic fused nuclei one OS 0 3 H group bonded directly to the (N a salts, including such K salt).
  • the tetracyclic fused nucleus represented by the formula (2) is a nucleus moiety of a steroid :
  • any hydrogen can be substituted by any group.
  • the steroid has, a compound in which a substituent having a skeleton as shown in the following formula (A) is bonded to the 17 position of the cyclopentaphenanthrene ring can be exemplified.
  • the steroid glycoside having a tetracyclic condensation nucleus represented by the formula (2) the above-mentioned formulas 33 B, 34 B 2, 39 A 2, 39 A 3 can be mentioned.
  • 7 4-2 and 7 4-4 are exemplified.
  • a compound in which a monosaccharide is bound to both the A nucleus and the D nucleus is used.
  • a compound in which a monosaccharide or a disaccharide is bound to either one of A nucleus and D nucleus is used.
  • the site to which the monosaccharide is attached is not particularly limited, and it may be attached at any site of carbon possessed by the monosaccharide.
  • Monosaccharides are bound either directly or indirectly when binding to the A nucleus or D nucleus. In the case of indirect bonding, the group interposed between them may be a group having a ketone, an ether, a double bond and the like in part or all in addition to the alkylene group.
  • the type of monosaccharide is not particularly limited. It may be of any carbon number such as pentose or hexose. In addition, it may be a disaccharide in which two monosaccharides are linked, and further, an OH group is partially an OR group (R is an alkyl group (for example, having about 1 to 3 carbon atoms, preferably a methyl group)) or It may be substituted by a group (for example, about 1 to 3 carbon atoms, preferably an acetyl group is preferable), and may be substituted by Z or hydrogen.
  • Examples of monosaccharides include xylose and the like.
  • the steroid glycoside is preferably a compound contained in an extract from an organism belonging to the starfish class.
  • NGF-related active substance of the present invention there is a step of separating a hydrophobic fraction from an organic solvent extract of an ornithode extracted with an organic solvent consisting of alcohol or acetone, silica gel and Z or dextran type carrier And a step of fractionating the hydrophobic fraction by a chromatography method using
  • the NGF-related active substance obtained by this production method is a group consisting of the above-mentioned novel steroid glycosides. It is desirable to contain at least one of these compounds.
  • the organic solvent extract can be obtained by mashing or pulverizing von ichthite and then immersing in an organic solvent, or by mashing or pulverizing von xfish in the presence of an organic solvent. It is desirable to carry out filtration to remove contaminants in order to facilitate the subsequent operation. You may use for the extraction operation in any state, such as frozen state and dried state, as it is. In particular, it is preferable to use lyophilization for the purpose of improving the handleability and degrading the contained components and suppressing loss.
  • the organic solvent can be appropriately selected from methanol, ethanol, alcohols such as n- , iso-propanol and the like (preferably methanol is selected).
  • any method that can separate the hydrophobic fraction may be employed.
  • it is a step of adsorbing and separating the hydrophobic fraction using a reverse phase carrier.
  • a reverse phase carrier As the carrier of the reverse phase system, an ODS system can be exemplified. Examples of chemical structures and product names include ODS (C18), reverse phase carriers other than 0DS, and synthetic adsorption resins such as DIAI 0 N and SEPABEADS.
  • the hydrophobic fraction adsorbed on the carrier can be eluted and separated quickly.
  • the hydrophobic fraction obtained in the previous step is fractionated by chromatography using a silica gel and / or dextran carrier (normal phase system).
  • a silica gel and / or dextran carrier normal phase system
  • the components contained in the hydrophobic fraction can be rapidly separated.
  • the preferred carrier Examples of the chemical structure and product name as the body include dextran based carriers such as silica gel and S mark hadex LH20.
  • (a) As a method of determining the degree of separation in principle, it can be performed by determining the strength of the NF-related activity and the strength of toxicity in the obtained fraction.
  • the measurement of NGF-related activity is determined by whether to induce neurite outgrowth using a test system using a general cell such as PC 12 cells. When inducing neurite outgrowth alone, it is a fraction showing NGF-like activity, and when enhancing the activity of NGF, it is a fraction showing NGF enhancing activity. When PC12 cells are damaged, it can be judged as toxic.
  • fraction having an R f value of less than 0.20 can be excluded from the aforementioned hydrophobic fraction and the remaining fraction can be used as the objective fraction.
  • separation conditions can be controlled so that components having an R f value of less than 0.2 do not mix.
  • a fraction having a more desirable NGF-related activity can be obtained by including a fraction having a value of 0.52 or more. It is also desirable to include fractions with an R f value less than 0.39.
  • the method for searching for an NGF-related active substance according to the present invention is characterized in that the tetracyclic fused nucleus described in the above formula (2) is used as a skeleton, and at least one of A nucleus and D nucleus directly or indirectly. Determine the presence or absence of NGF-related activity by whether or not it contains a steroid glycoside to be bound Do.
  • the items described in the section on NGF-related active substances above are valid as they are, and thus further description is omitted.
  • a compound (aglycone having a tetracyclic condensation nucleus) in which a tetracyclic condensation nucleus represented by the formula (2) is bonded to a monosaccharide (determination of whether or not it is contained as represented by saponin etc.) Is an easy compound. Therefore, the relatively easy operation of detecting aglycone having a four-ring condensation nucleus can roughly narrow down potential candidates for NGF-related active substances and their source animals (plants), and the time required for the search can be obtained. It can be greatly shortened.
  • the bonding position and the number of bonds of the monosaccharide may be determined to determine whether the compound corresponds to the above-mentioned formula (2).
  • the number of linkages and the linkage position of monosaccharides can be determined relatively easily, it is a method that is simple overall as compared with the conventional methods of screening NGF related active substances widely. For example, the content ratio of monosaccharides is measured, and the value is compared with the concentration of these steroid glycosides, etc., to calculate the number of bonds of monosaccharides to the tetracyclic condensation nucleus represented by the formula (2).
  • This substance (5 ⁇ g / mL) depletes neurite outgrowth to 26% of PC 12 cells and does not extend the neurite in the presence of trace NGF (1.5 ng / mL).
  • the protrusion extension activity was enhanced to 77%.
  • f r. B (572 mg, f r. 27-29) and f r. C (93 mg, fr. 30-34) alone did not show protrusion extension activity, but NGF (1.5 The activity of ng / mL was increased to 27% (fr. B) and 45% (fr. C). The subsequent high polar fractions f r. D (23 lmg) and f r. E (988 mg) showed cytotoxicity before exhibiting NGF-related activity.
  • Rat adrenal medulla pheochromocytoma-derived PC 12 cells were obtained from Riken Cell Bank. Cryopreserved cells (2 xl 0 4 cells) medium - and washed with (MEME- 10% fetal bovine serum 5% horse serum), with medium 1 OML plated on 9 cm Petri dish, 5% Rei_0 2 atmosphere under 37 Stationary culture was performed for 1 week. Harvest cells and use fresh medium 2 x 10 5 After repeating the subculturing procedure of 1 week of culture dilution for 1 week after dilution into cells / dish, harvested cells were used for the test (up to 12 passages). In the following, culture is performed at 37 ° C. in a 5% CO 2 atmosphere.
  • the neurite outgrowth activity is the value of NGF-like activity when added alone, and the neurite when further added with NGF added at a concentration that does not induce neurite outgrowth (1.5 ng / mL).
  • the elongation activity was taken as the value of NGF enhancing activity.
  • f r. 21 (17. 6 mg) was purified by HPLC (solvent 40% MeCN, other conditions such as column are the same as above), and a novel steroid glycoside, xanthasteloside 40 B ( 15. Obtained Omg).
  • fr. 22 (52.5 mg) was purified by HPLC (under the same conditions) to obtain acantasterosteroside 40A (10.7 mg), which is a novel steroidal glycoside.
  • fantaleuside 34 C (5.6 mg), which is a novel steroid glycoside derived from f r. 13 (12.6 mg), and two novel compounds from f r. 20 (29.
  • FIG. 1 shows the values of the steroid glycosides and NGF-related activities isolated from the peaks obtained in the first HP LC and their respective peak powers. In FIG. 1, a line is drawn from the peak where the steroid glycoside is isolated.
  • Peaks from which these steroid glycosides were isolated are, from the left (small retention time) under the above conditions, peakl (fr. 12): 53-56 minutes; peak2 (fr. 13): 56 -60 minutes; peak 3 (fr. 1 7): 77-81 minutes; peak 4 (fr. 1 9): 87-90 minutes; peak 5 (fr. 20): 90-96 minutes; peak 6 (fr. 21): 96 -105; peak7 (fr. 22): 106-125 It can be distinguished from the fact that it is a large peak appearing in the range of about 125 minutes. The target compound can be easily isolated by separating the peaks with reference to these retention times.
  • FIG. 2 a photomicrograph showing the appearance of PC12 cells after inducing neurite outgrowth using Acanthasteroside 4 OA and NGF is shown in FIG.
  • the upper right of Fig. 2 is the control, and when nothing is added, the cell shape does not change, but when Aquantasteloside 4 OA (lower left) and NGF (lower right) are added. From the cells, it can be seen that many projections are elongated.
  • the above active fraction f r. C (93 Omg) was purified by HPLC.
  • the conditions are as follows: Column ODDSevelosil-UG-5 ( ⁇ 28 x 250), solvent 70% MeOH, flow rate 18 ml / min, detection wavelength 205 nm, injection in two divided doses. As shown in FIG. 3, five fractions (Fr. C-1 to C-5) were obtained based on the chromatographic peak.
  • Table 5 shows the results of measurement of the NGF-like activity and the NGF-strong activity of each steroid glycoside shown in FIG. Furthermore, in the compound types shown in Table 5
  • the terroid nucleus is a structure corresponding to the tetracyclic condensation nucleus shown in Formula (2), and is slightly different for each compound. And from the top of Table 5, one in which one monosaccharide is bonded to A nucleus shown in formula (2) (a), one in which one monosaccharide is bonded to both A nucleus and D nucleus ( ⁇ ), And, it can be classified into three major types of those in which two monosaccharides (disaccharides) are linked to the D nucleus ( ⁇ ).
  • NGF-like activity is confirmed only in type j3, type E, J3 Since both of n and y show NGF enhancing activity, it can be expected that NGF-like activity can be expected from a compound having a structure of (1) type 3; It can be inferred that a compound in which one monosaccharide or disaccharide is bound to a steroid nucleus exemplified in and the like has NGF-related activity.
  • (l) when a compound having NGF-like activity is required it can be obtained by searching for a compound having a structure of type / 3, (2) when a compound having NGF enhancing activity is required It can be inferred that the compound can be obtained by searching for a compound in which one monosaccharide or disaccharide is bound to the steroid nucleus.
  • novel steroidal glycosides (acanthasteroside 4 OA, B, 34 B, C and 39 A) of the present invention show no toxicity and their activity is recognized up to about 40 ⁇ M. In addition, a sufficient effect is exhibited even at a concentration of about 20 ⁇ m.
  • the NGF-related activity of these steroidal glycosides is higher than that of compounds for which the NGF-related activity is conventionally known.
  • the NGF-like activity and the NGF enhancing activity of Compound 35-2 and Compound 42-2 were also measured in the same manner as in (1). The results are shown in Table 6.
  • compound 64-3 corresponding to type y also shows high NGF-like activity and strong NGF activity. However, as predicted from Table 5, the NGF-like activity is slightly weaker than the compound corresponding to type / 3.
  • test sample The effect of the above-mentioned f r. A (hereinafter referred to as “test sample”) on learning memory impairment when administered to mice was examined.
  • mice Eight to ten months old ICR male mice (aged group) were used. Every evening after weight measurement, each group was administered subcutaneously. The dose of the test sample, 1 kg body weight per lmg or 10 m g and so as to test sample group was dissolved in physiological saline (10 animals each), and the group administered neat saline (10 mice) did. The administration was for 14 days. After administration for 14 days, a Y-shaped maze test was performed according to a conventional method. As a control group, 6 week old ICR male mice (Young group: 10) were similarly subcutaneously administered with physiological saline.
  • novel steroidal glycosides of the present invention can be expected to have NGF related activity and the like.
  • Substances having NGF-related activity are expected to exert effective actions for treating dementia and improving learning ability as pharmacological actions, and their application as drugs can be expected. Therefore, they have industrial applicability as to methods for producing and searching for these NF-related active substances.

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Abstract

La présente invention concerne un nouveau glycoside stéroïdien ayant une activité associée au NGF, représenté par la formule générale (1). Ce glycoside stéroïdien a une activité associée au NGF.
PCT/JP2006/304036 2005-02-25 2006-02-24 Nouveau glycoside steroidien, substance active associée au ngf, procede pour les produire, procede de depstage de ceux-ci et agent de prevention d’un dysfonctionnement cerebral WO2006090910A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008273856A (ja) * 2007-04-26 2008-11-13 Ryuei Soken:Kk ヒトデエキスを有効成分とする物質
WO2010095741A1 (fr) * 2009-02-23 2010-08-26 国立大学法人名古屋大学 Nouveau dérivé de stéroïde et son procédé de production et préparation pharmaceutique comprenant le nouveau dérivé de stéroïde
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Publication number Priority date Publication date Assignee Title
JP2008273856A (ja) * 2007-04-26 2008-11-13 Ryuei Soken:Kk ヒトデエキスを有効成分とする物質
WO2010095741A1 (fr) * 2009-02-23 2010-08-26 国立大学法人名古屋大学 Nouveau dérivé de stéroïde et son procédé de production et préparation pharmaceutique comprenant le nouveau dérivé de stéroïde
CN104931598A (zh) * 2014-03-21 2015-09-23 舒泰神（北京）生物制药股份有限公司 一种神经生长因子制剂中神经生长因子含量的测定方法

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