CN102512405B - One class long-chain fatty acid derivative or the plant extract containing it are preparing the application in the medicine suppressing activity of aromatizing enzyme - Google Patents
One class long-chain fatty acid derivative or the plant extract containing it are preparing the application in the medicine suppressing activity of aromatizing enzyme Download PDFInfo
- Publication number
- CN102512405B CN102512405B CN201110370461.4A CN201110370461A CN102512405B CN 102512405 B CN102512405 B CN 102512405B CN 201110370461 A CN201110370461 A CN 201110370461A CN 102512405 B CN102512405 B CN 102512405B
- Authority
- CN
- China
- Prior art keywords
- application
- fatty acid
- chain fatty
- acid derivative
- plant extract
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The application that the plant extract that the invention discloses a class long-chain fatty acid derivative as shown in Equation 5 or contain it suppresses activity of aromatizing enzyme preparation, prevention in preparation or treats in the pharmaceutical composition of prostatoplasia diseases.The new application of this compound has been opened up in application of the present invention, simultaneously also for the prevention and therapy of the disease in above-mentioned field provides new approach.
formula 5
Description
The divisional application that the application is the applying date is on April 30th, 2008, application number is 200810036931.1, denomination of invention is the application of " a class long-chain fatty acid derivative or the plant extract containing it are suppressing the application in activity of aromatizing enzyme ".
Technical field
The present invention relates to the new opplication of a class long-chain fatty acid derivative or its plant extract.
Background technology
Benign prostatic hyperplasia (benign prostatic hyperplasia, BPH) is the common physiology pathological changes of elderly men, is called hyperplasia of prostate when pathological changes causes and urinates and the series of symptoms such as to block.External 1075 routine Autopsy Reports show: 25 ~ 30 years old time, and the male of 10% can see early stage prostatic hyperplasia pathological changes under the microscope; With advancing age, through the incidence rate also corresponding increase of the prostatic hyperplasia of histodiagnosis; To 51 ~ 60 years old, its sickness rate increased to 75%; During to 85 years old, about there is the prostatic hyperplasia pathological changes that the male of 90% learns in a organized way.Therefore along with the acceleration of China's aged tendency of population, the sickness rate of the prostatic hyperplasia caused by old-age group constantly rises, benign prostate hyperplasia also more and more becomes China's major issue urgently to be resolved hurrily.The sickness rate of benign prostatic hyperplasia is very high, but its pathogeny is illustrated so far not yet completely.Prostatic hyperplasia may be the disease of one group of multi-pathogenesis, and its pathogenesis is also complicated.The direction of BPH Drug therapy is exactly for its various possible pathogenesis and existing factor, theoretical and bibliographical information according to these, we sum up multiple maturation with the action target spot of new anti-BPH medicine, comprise α 1-adrenoceptor, 5α-reductase, aromatase, phosphodiesterase-5, glycolytic ferment and COX-2 etc.
At present, the medicine being used for the treatment of prostatic hyperplasia clinically mainly contains: α 1-adrenergic receptor antagonist, 5α-reductase inhibitor, natural product preparation etc.Because prostatic hyperplasia pathogenic factor is intricate and need Long-term taking medicine, certain side effect has been there is in the synthetic drug such as alpha 1-receptor blocker, 5α-reductase inhibitor only for a certain specific target spot in long-term taking, as hypotension, sexual impotence, sexual dysfunction, headache etc., and therapeutic effect is not ideal enough, thus limit the application of these medicines in Treatment of Benign Prostatic Hyperplasia.Natural product preparation has globality, Mutiple Targets and multicomponent synergistic feature, particularly Pollen Preparations does not affect hormone in vivo secretion balance, and toxic and side effects is little, is applicable to the feature of long-term taking, is more and more subject to the welcome of patient.
Zoopery and clinical research all show, estrogen all plays very important role in the generation, evolution of prostatic hyperplasia.Along with the increase at age, the estrogen in males is comparatively stable or have increased slightly, compared with young man, in elderly men blood plasma and prostata tissue female/Androgen Ratio raises.And the change of this gonadal hormone balance may be induced Prostate gland stroma active thus draw BPH.Have research display, in prostatic stromal hyperplasia, the estrogen of bonding state can synthesize and extracellular matrix secretion albumen by active cell, forms the fibrous connective tissue of one deck densification, and then participate in developing of prostatic hyperplasia at cell peripheral.In initial interstitial proliferation, the effect of estrogen is main; In the process of prostatic hyperplasia, female androgen has synergism, and thus someone claims estrogen to be the stimulant that Prostate gland stroma grows.In view of the important function of estrogen in BPH, the method suppressing estrogen synthesis can be used, as used arimedex treatment prostatic hyperplasia.Estrogen in males is mainly transformed by androgen precurosor, and P450 aromatase is key enzyme and the rate-limiting enzyme of this transition process.The mixed-function oxidase that it is take NADPH as coenzyme, Cytochrome P450 is medium.In theory, arimedex has the potential effect of all hormone-dependent diseases such as treatment benign prostatic hyperplasia.And the Experimental report of more existing use arimedex treatment BPH at present: a kind of therapeutic outcome display of more weak arimedex testolactone, the BPH symptom of 50% is improved, can voluntary micturition, prostate volume reduce 30%, residual urine volume obviously reduces.A kind of novel aromatic enzyme inhibitor TZA-2237 of uniqueness of Michaud report carries out animal (dog) experiment, finds that TZA-2237 can effectively suppress androgen and estrogen, can cause the prostatic stromal cell atrophy of dog.But about also few with the clinical report of aromatase treatment BPH, its curative effect also needs further checking.Along with the clinical understanding gradually acted in BPH estrogen, developing new aromatase inhibitor in treatment BPH may be one of direction of next stage Drug therapy.
In recent years, people, by medicine efficacy screening, have found that in natural product the multiclass compounds such as flavone, coumarin, terpenoid, fatty acid and polyphenol have aromatic enzyme-tion suppressioning activity, and have obtained a series of derivant by structure of modification.Bibliographical information crosses the suppression activity of aromatizing enzyme of free fatty.(J.Nat.Prod.2006，69，700-703；Cancer Res 2006，66(24)：12026-12033)
Summary of the invention
Technical problem to be solved by this invention is that the prevention or treatment for being carried out prostatoplasia diseases by suppression activity of aromatizing enzyme provides a kind of new way, and discloses the new opplication of a class long-chain fatty acid derivative.
The invention discloses a class long-chain fatty acid derivative as shown in Equation 5 or to suppress the application in activity of aromatizing enzyme preparation containing its plant extract in preparation, and the application further in the pharmaceutical composition of preparation prevention or treatment prostatoplasia diseases.
Formula 5
Compound is as shown in Equation 5 preferably:
(Structural Identification can see document: A.E.Karaulov for N-(2-ethoxy) linolenamide as shown in Equation 1, V.G.RybinD, V.Kuklev, V.N.Akulin.Chemistry of Natural Compounds.2004,40 (3): 222-226):
Formula 1
(Structural Identification can see document: Han Huiying for linolenic acid fructoside as shown in Equation 2, " research of QIANLIEKANG and raw material Pollen Brassicae campestris Brassica napus L_pollen active component thereof ", Shenyang Pharmaceutical University's master thesis, 2004,11-80, CNKi data base, ten-thousand-ton train searching system):
Formula 2
(Structural Identification can see document: P.Junkui for Palmic acid sorbitol ester as shown in Equation 3, A.Shuji.Biocatalysis and Biotransformation, 2004,22 (4): 269-274.G.W.Schnarr, D.M.Wyas, W.A.Szarek, et al.J Chem Soc Perkin I, 1979,2:4961-4966):
Formula 3
Or dihydroxy-octa-decadienoic acid as shown in Equation 4 (Structural Identification can see document: E.H.Oliw.Biochemical and Biophysical Research Communications.1983,111 (2): 644-651.).
Formula 4
In above-claimed cpd, the preparation method of N-(2-ethoxy) linolenamide and linolenic acid fructoside all can with reference to above-mentioned document: Han Huiying, " research of QIANLIEKANG and raw material Pollen Brassicae campestris Brassica napus L_pollen active component thereof ", 2004,11-80.
In the present invention, described plant extract can be Pollen Brassicae campestris or Pollen Maydis extract etc., is preferably Pollen Brassicae campestris extract.
Long-chain fatty acid derivative of the present invention or containing its plant extract, can process for preparing medicine routinely, adds conventional excipient or pharmaceutically acceptable carrier, can obtain the pharmaceutical composition of various dosage form.It adds relevant excipient at the mixture of each single-activity composition or two or more active component, makes tablet, capsule, soft capsule, liquid preparation, granule, soft extract, pill, suspending agent, dispersant, syrup, suppository, injection.Excipient wherein comprises binding agent, as polyvinylpyrrolidone, hydroxypropyl cellulose etc.; Disintegrating agent, as sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose etc.; Diluent, as starch, Icing Sugar, dextrin, microcrystalline Cellulose, mannitol, lactose, Semen sojae atricolor wet goods, lubricant, as magnesium stearate, Pulvis Talci; Sweeting agent, as sucrose, fructose, aspartame etc.; Stabilizing agent, as sodium carboxymethyl cellulose, cyclodextrin etc.; Antiseptic, as ethylparaben, sodium benzoate etc.The dosage of the active component of described pharmaceutical composition is preferably 0.025 ~ 0.10mg/Kg body weight/day.
The reagent that the present invention is used and raw material are all commercially.
Positive progressive effect of the present invention is: the invention discloses a class long-chain fatty acid derivative as shown in Equation 5 or the plant extract containing it has the effect significantly suppressing activity of aromatizing enzyme, effectively can prevent and treat prostatoplasia diseases.
Detailed description of the invention
Further illustrate the present invention by embodiment below, but the present invention is not limited.
The preparation of embodiment 1N-(2-ethoxy) linolenamide, dihydroxy-octa-decadienoic acid, linolenic acid fructoside and Palmic acid sorbitol ester
1) supercritical extraction: by commercially available rape pollen with broken wall (production of Xuancheng City of Anhui Province hundred health apiculture) 60 DEG C of drying under reduced pressure 24 hours, then by dried pollen (processed by breaking wall) at 40 DEG C, extraction kettle pressure 40MPa, separation reactor I temperature 35 DEG C, pressure 12MPa, separation reactor I I temperature 25 DEG C, pressure 5MPa, with the concentration of pollen weight 8% weight for 95v/v% ethanol extracts 2.0 hours for entrainer carries out supercritical carbon dioxide (the circulation consumption of 45L/ hour), obtain supercritical extraction part, collect supercritical extract.
2) macroporous resin enrichment: adopt macroporous resin column chromatography (the DA201 resin of 10 times of sample qualities, Tian Jinhui reaches Chemical Co., Ltd. or Anhui Samsung resin Science and Technology Ltd., the pillar of 120cm*6cm specification), further enrichment, purification are carried out to supercritical extraction part.Macroporous resin column on the extract that supercritical extraction is obtained.Adopt the ethanol water of 65% volumetric concentration of 10 times of column volumes to carry out eluting, collect eluent, decompression and solvent recovery, evaporate to dryness, obtains effective site.
3) column chromatography: above-mentioned effective site is mixed silica gel upper prop, carry out silica gel (300-400 order) column chromatography and (decuple the silica gel of sample quality, the pillar of 120cm*6cm specification), gradient elution is carried out with petroleum ether-ethyl acetate, gradient is volume ratio 10: 1 → 8: 1 → 6: 1 → 4: 1 → 2: 1 → 1: 1 → 1: 2, each gradient mixed solvent amount used is 6 times of column volumes, obtain I ~ VII part, collect above-mentioned gradient 2: 1 and 1: 1 elution fraction respectively, solvent evaporate to dryness, obtains elution fraction V and elution fraction VI.
4) purification: the elution fraction V of above-mentioned steps gained is mixed silica gel upper prop, (10 times to the silica gel of sample quality to carry out silica gel (300-400 order) column chromatography, the pillar of 80cm*4cm specification), with the chloroform-methanol of 10 times of column volumes (volume ratio 20: 1) eluting, the chromatographic solution of each collection 1/4th column volume, collect front 30 elution fraction, 2nd ~ 5 stream parts merge, decompression and solvent recovery, obtain compound N-(2-ethoxy) linolenamide, 21st ~ 24 stream parts merge, decompression and solvent recovery, obtain compound dihydroxy-octa-decadienoic acid.
(10 times to the silica gel of sample quality the elution fraction VI of above-mentioned steps gained to be carried out silica gel (300-400 order) column chromatography, the pillar of 80cm*4cm), with chloroform-methanol (volume ratio 10: the 1) eluting of 10 times of column volumes, the chromatographic solution of each collection 1/4th column volume, collect 30 elution fraction, 1st ~ 3 stream parts merge, decompression and solvent recovery, obtain compound linolenic acid fructoside, 20th ~ 22 stream parts merge, decompression and solvent recovery, obtains compound Palmic acid sorbitol ester.
The preparation of embodiment 2N-(2-ethoxy) linolenamide, 1-glyceryl linolenate, dihydroxy-octa-decadienoic acid, linolenic acid fructoside and Palmic acid sorbitol ester
1) extract: get Pollen Brassicae campestris after breaking cellular wall, pulverizing, is 95% ethanol water reflux 3 times with the ratio volumetric concentration of 10ml/g Pollen Brassicae campestris, filters, merging filtrate, decompression and solvent recovery, obtains the fluid extract that relative density is 1.28, soluble in water with the ratio of 2ml water/g fluid extract, use petroleum ether, chloroform and extraction into ethyl acetate successively, each extractant consumption is aqueous solution equal-volume, often kind of solvent extraction repeatedly, near colorless.Get ethyl acetate extraction part, decompression and solvent recovery, evaporate to dryness, obtain effective site.
2) column chromatography: above-mentioned effective site is mixed silica gel upper prop, (10 times to the silica gel of sample quality to carry out silica gel (300-400 order) column chromatography, the pillar of 120cm*6cm specification), gradient elution is carried out with petroleum ether-ethyl acetate, gradient is volume ratio 10: 1 → 8: 1 → 6: 1 → 4: 1 → 2: 1 → 1: 1 → 1: 2, each gradient mixed solvent amount used is 6 times of column volumes, obtain I ~ VII part, collect above-mentioned gradient 2: 1 and 1: 1 elution fraction respectively, solvent evaporate to dryness, obtains elution fraction V and elution fraction VI.
3) purification: the elution fraction V of above-mentioned steps gained is mixed silica gel upper prop, (10 times to the silica gel of sample quality to carry out silica gel (300-400 order) column chromatography, the pillar of 80cm*4cm specification), with the chloroform-methanol of 10 times of column volumes (volume ratio 20: 1) eluting, the chromatographic solution of each collection 1/4th column volume, collect front 30 elution fraction, 2nd ~ 5 stream parts merge, decompression and solvent recovery, obtain compound N-(2-ethoxy) linolenamide, 21st ~ 24 stream parts merge, decompression and solvent recovery, obtain compound dihydroxy-octa-decadienoic acid.
(10 times to the silica gel of sample quality the elution fraction VI of above-mentioned steps gained to be carried out silica gel (300-400 order) column chromatography, the pillar of 80cm*4cm), with the chloroform-methanol of 10 times of column volumes (volume ratio 10: 1) eluting, the chromatographic solution of each collection 1/4th column volume, collect first three ten elution fraction, 1st ~ 3 stream parts merge, decompression and solvent recovery, obtain compound linolenic acid fructoside, 20th ~ 22 stream parts merge, decompression and solvent recovery, obtains compound Palmic acid sorbitol ester.
Effect example
The active component of prevention and therapy prostatoplasia diseases of the present invention suppresses activity of aromatizing enzyme better, specific experiment mode and data as follows.Wherein, linolenic acid available from Sigma.
Method of testing list of references is: Quan Haitian, Lou Liguang. " foundation of arimedex screening model " Chinese Pharmacological Bulletin, 2004,20 (10): 1189-1192.
With the microsome of the Placenta Hominis enzyme source as aromatase, with [1 β-
3h] androstenedione as reaction substrate, by recording product
3h
2the radiant of O detects the activity of aromatase, counts with liquid scintillation counter
3h
2the emissivity of O, computerized compound is to the inhibitory action of aromatase.
One, material and instrument
The Placenta Hominis of people takes from Jing'an District, Shanghai City hospital for obstetrics and gynaecology.[1 β-
3h] androstenedione (958.3TBqmol
-1) be Perkin Elmer Life Sciences Inc product; Androstenedione, reference substance Aminoglutethimide, NADPH are Sigma Products; Test sample is made by oneself.Dextran T 70 is Amersham Bioscience Products; Other reagent are domestic analytical pure.
Supercentrifuge is purchased from HITACHI Co, and refrigerated centrifuge is purchased from International Equipment Co., and-86 DEG C of ultra cold storage freezers are purchased from Thermo Electron Co, and radiosiotope detector is purchased from Beckman Co..
Two, method
1. MC preparation
Institute all carries out at 0 ~ 4 DEG C in steps.Be placed at once on ice after Placenta Hominis obtains, removing chorion and trunk, use 0.01molL
-1shred with shears after PBS (including 1%KCl) cleaning, use 0101molL
-1pBS (includes 0124molL
-1sucrose and 0.5 μm of olL
-1androstenedione) carry out homogenate.Centrifugal 900 × g 60min.Abandon precipitation, the centrifugal 10000 × g 60min of supernatant is with precipitation line plastochondria composition.Supernatant more centrifugal 125000 × g 60min can obtain microsome fraction.Precipitation uses 0.01molL again
-1pBS (includes 0.1mmolL
-1eDTA, 0.5 μm of olL
-1androstenedione) resuspension, the albumen of suspension is in order to 0.01molL
-1pBS is that to be dissolved to final concentration of protein be 2 ~ 3gL to 0.1% NP-40 of solvent
-1.
2. the foundation of enzyme reaction system
Reaction substrate [1 β-
3h] androstenedione is kept in dehydrated alcohol in advance, 0.067molL during reaction
-1pBS dilutes, and the final concentration of ethanol is less than 1%.Reaction is with 0.067molL
-1pBS is buffer, also comprises 0.01ml Microsome preparation liquid in the reaction system of 0.4ml, 50pmol [1 β-
3h] androstenedione and 0.20mg NADPH.Reaction is carried out at 37 DEG C, starts, carries out 2,5,10,15min respectively, then add the trichloroacetic acid cessation reaction 1min of 0.4ml 20% to add NADPH.Add the chloroform of 1.0ml pre-cooling after termination, centrifugal 3200 × g 10min after continuation vibration 10min, sucts honest and upright and thrifty 0.8ml, then adds 0.8ml 5%dextran coated charcoal, and 37 DEG C are continued vibration temperature and bathe 30min.Centrifugal 3200 × g the 10min of mixed liquor.Get supernatant to measure
3the radiant of H, blank is with without MC reactant liquor.Sample concentration is 100 μ g/ml, adds before NADPH adds.
3.K
mand V
maxmensuration
In 0.4ml reaction system, the concentration of reference substance Aminoglutethimide gets 1 respectively, 2,4,12.5,25 μ g/ml, and the concentration of test sample gets 10 respectively, 25,50,100,200 μ g/ml, reaction 5min, and in reaction system, other compositions and step are with 2.
4. measure the K of substrate
mand V
max
At NADPH and O excessive far away
2deposit in case, the catalytic reaction of aromatase is single substrate reactions.Change [1 β-
3h] concentration of androstenedione, and control product amount all the time and be less than 5% of amount of substrate, use meter-Meng Shi equation, adopt 1/v-1/ [S] double-reciprocal plot method, calculate K
mand V
max.
5. measure the suppression ratio of reference substance and test sample
In 0.4ml reaction system, reference substance concentration is 1 μ g/ml, and test sample concentration is 100 μ g/ml, reaction 5min, and other compositions of system and step, with 2, measure suppression ratio.Result is as shown in table 1.
Table 1 compound suppresses the test result of activity of aromatizing enzyme
| Compound | Suppression ratio (100 μ g/mL) |
| N-(2-ethoxy) linolenamide | 79％ |
| Linolenic acid fructoside | 56％ |
| Palmic acid sorbitol ester | 51％ |
| Dihydroxy-octa-decadienoic acid | 51％ |
| Linolenic acid | 55％ |
As seen from the above table, four kinds of long-chain fatty acid derivatives in the present invention all have stronger aromatic enzyme-tion suppressioning activity, and the aromatic enzyme-tion suppressioning activity of two kinds of long-chain fatty acid derivatives has wherein exceeded free fatty linolenic acid.
Claims (1)
1. Palmic acid sorbitol ester as shown in Equation 3, or dihydroxy-octa-decadienoic acid is as shown in Equation 4 as the application of sole active agent in the pharmaceutical composition of preparation prevention or treatment prostatoplasia diseases;
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100369311A CN101569618B (en) | 2008-04-30 | 2008-04-30 | Application of long-chain fatty acid derivative or plant extracts containing same in inhibiting the activity of aromatizing enzyme |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008100369311A Division CN101569618B (en) | 2008-04-30 | 2008-04-30 | Application of long-chain fatty acid derivative or plant extracts containing same in inhibiting the activity of aromatizing enzyme |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102512405A CN102512405A (en) | 2012-06-27 |
| CN102512405B true CN102512405B (en) | 2015-08-05 |
Family
ID=41229191
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110370461.4A Active CN102512405B (en) | 2008-04-30 | 2008-04-30 | One class long-chain fatty acid derivative or the plant extract containing it are preparing the application in the medicine suppressing activity of aromatizing enzyme |
| CN2008100369311A Active CN101569618B (en) | 2008-04-30 | 2008-04-30 | Application of long-chain fatty acid derivative or plant extracts containing same in inhibiting the activity of aromatizing enzyme |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008100369311A Active CN101569618B (en) | 2008-04-30 | 2008-04-30 | Application of long-chain fatty acid derivative or plant extracts containing same in inhibiting the activity of aromatizing enzyme |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN102512405B (en) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014037832A2 (en) | 2012-09-06 | 2014-03-13 | Mahesh Kandula | Compositions and methods for the treatment of epilepsy and neurological diseases |
| EP2847158A4 (en) | 2012-05-07 | 2015-12-30 | Cellix Bio Private Ltd | Compositions and methods for treatment of neuromuscular disorders and neurodegenerative disorders |
| US9399634B2 (en) | 2012-05-07 | 2016-07-26 | Cellix Bio Private Limited | Compositions and methods for the treatment of depression |
| CA2872975A1 (en) | 2012-05-07 | 2013-11-14 | Cellixbio Private Limited | Compositions and methods for the treatment of neurological disorders |
| US9434704B2 (en) | 2012-05-08 | 2016-09-06 | Cellix Bio Private Limited | Compositions and methods for the treatment of neurological degenerative disorders |
| US9522884B2 (en) | 2012-05-08 | 2016-12-20 | Cellix Bio Private Limited | Compositions and methods for the treatment of metabolic disorders |
| US9403826B2 (en) | 2012-05-08 | 2016-08-02 | Cellix Bio Private Limited | Compositions and methods for the treatment of inflammatory disorders |
| WO2013168025A1 (en) | 2012-05-08 | 2013-11-14 | Mahesh Kandula | Compositions and methods for treatment of blood clotting disorders |
| US9266823B2 (en) | 2012-05-08 | 2016-02-23 | Cellix Bio Private Limited | Compositions and methods for the treatment of parkinson's disease |
| US9499527B2 (en) | 2012-05-10 | 2016-11-22 | Cellix Bio Private Limited | Compositions and methods for the treatment of familial amyloid polyneuropathy |
| WO2013168001A1 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of moderate to severe pain |
| US9339484B2 (en) | 2012-05-10 | 2016-05-17 | Cellix Bio Private Limited | Compositions and methods for the treatment of restless leg syndrome and fibromyalgia |
| WO2013168007A1 (en) * | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of cardiovascular and neurological diseases |
| WO2013168011A1 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of chronic pain |
| WO2013168000A1 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of severe pain |
| WO2013168012A1 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of respiratory disorders |
| US9315461B2 (en) | 2012-05-10 | 2016-04-19 | Cellix Bio Private Limited | Compositions and methods for the treatment of neurologic diseases |
| WO2013168015A1 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of asthma and allergy |
| WO2013167997A2 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of metabolic syndrome |
| US9233161B2 (en) | 2012-05-10 | 2016-01-12 | Cellix Bio Private Limited | Compositions and methods for the treatment of neurological conditions |
| US9346742B2 (en) | 2012-05-10 | 2016-05-24 | Cellix Bio Private Limited | Compositions and methods for the treatment of fibromyalgia pain |
| SG11201407318UA (en) | 2012-05-10 | 2014-12-30 | Cellix Bio Private Ltd | Compositions and methods for the treatment of metabolic syndrome |
| WO2013168033A1 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for treatment of neurologic diseases |
| JP6202287B2 (en) | 2012-05-23 | 2017-09-27 | セリックスビオ プライヴェート リミテッド | Compositions and methods for the treatment of inflammatory bowel disease |
| JP2015518854A (en) | 2012-05-23 | 2015-07-06 | セリックスビオ プライヴェート リミテッド | Compositions and methods for the treatment of multiple sclerosis |
| JP2015518855A (en) | 2012-05-23 | 2015-07-06 | セリックスビオ プライヴェート リミテッド | Compositions and methods for the treatment of mucositis |
| WO2013175347A2 (en) | 2012-05-23 | 2013-11-28 | Mahesh Kandula | Compositions and methods for the treatment of respiratory disorders |
| US9492409B2 (en) | 2012-05-23 | 2016-11-15 | Cellix Bio Private Limited | Compositions and methods for the treatment of local pain |
| US9434729B2 (en) | 2012-05-23 | 2016-09-06 | Cellix Bio Private Limited | Compositions and methods for the treatment of periodontitis and rheumatoid arthritis |
| US9108942B1 (en) | 2014-11-05 | 2015-08-18 | Mahesh Kandula | Compositions and methods for the treatment of moderate to severe pain |
| WO2014020480A2 (en) | 2012-08-03 | 2014-02-06 | Mahesh Kandula | Compositions and methods for the treatment migraine and neurologic diseases |
| US9624168B2 (en) | 2012-09-06 | 2017-04-18 | Cellix Bio Private Limited | Compositions and methods for the treatment inflammation and lipid disorders |
| SG11201407325YA (en) | 2012-09-08 | 2014-12-30 | Cellix Bio Private Ltd | Compositions and methods for treatment of inflammation and lipid disorders |
| US9333187B1 (en) | 2013-05-15 | 2016-05-10 | Cellix Bio Private Limited | Compositions and methods for the treatment of inflammatory bowel disease |
| EP3004049B1 (en) | 2013-06-04 | 2018-09-05 | Cellixbio Private Limited | Compositions and methods for the treatment of diabetes and pre-diabetes |
| US9096537B1 (en) | 2014-12-31 | 2015-08-04 | Mahesh Kandula | Compositions and methods for the treatment of mucositis |
| EP3240779B1 (en) | 2014-09-26 | 2020-10-28 | Cellixbio Private Limited | Compositions and methods for the treatment of epilepsy and neurological disorders |
| EP3201168B1 (en) | 2014-09-29 | 2020-03-18 | Cellix Bio Private Limited | Compounds and compositions for the treatment of multiple sclerosis |
| CA2965449C (en) | 2014-10-27 | 2020-11-10 | Cellix Bio Private Limited | Three component salts of fumaric acid monomethyl ester with piperazine or ethylene diamine for the treatment of multiple sclerosis |
| US10208014B2 (en) | 2014-11-05 | 2019-02-19 | Cellix Bio Private Limited | Compositions and methods for the treatment of neurological disorders |
| US9173877B1 (en) | 2014-11-05 | 2015-11-03 | Cellix Bio Private Limited | Compositions and methods for the treatment of local pain |
| US9175008B1 (en) | 2014-11-05 | 2015-11-03 | Cellix Bio Private Limited | Prodrugs of anti-platelet agents |
| US9150557B1 (en) | 2014-11-05 | 2015-10-06 | Cellix Bio Private Limited | Compositions and methods for the treatment of hyperglycemia |
| US9321716B1 (en) | 2014-11-05 | 2016-04-26 | Cellix Bio Private Limited | Compositions and methods for the treatment of metabolic syndrome |
| US9290486B1 (en) | 2014-11-05 | 2016-03-22 | Cellix Bio Private Limited | Compositions and methods for the treatment of epilepsy |
| US9284287B1 (en) | 2014-11-05 | 2016-03-15 | Cellix Bio Private Limited | Compositions and methods for the suppression of carbonic anhydrase activity |
| US9932294B2 (en) | 2014-12-01 | 2018-04-03 | Cellix Bio Private Limited | Compositions and methods for the treatment of multiple sclerosis |
| US9206111B1 (en) | 2014-12-17 | 2015-12-08 | Cellix Bio Private Limited | Compositions and methods for the treatment of neurological diseases |
| EP3242869B1 (en) | 2015-01-06 | 2021-10-27 | Cellixbio Private Limited | Compositions and methods for the treatment of inflammation and pain |
| CN109796367B (en) * | 2019-03-29 | 2022-02-15 | 广东工业大学 | Preparation method and application of N-fatty acyl ethanolamine product |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1672678A (en) * | 2004-05-03 | 2005-09-28 | 深圳微芯生物科技有限责任公司 | Separation and extraction of natural active long-chain fatty acid component for preventing and treating prostatosis and the prepn and application of its medicine prepn |
| CN1857361A (en) * | 2006-03-17 | 2006-11-08 | 崔彬 | Medicine for treating prostatosis and its preparing method and application |
-
2008
- 2008-04-30 CN CN201110370461.4A patent/CN102512405B/en active Active
- 2008-04-30 CN CN2008100369311A patent/CN101569618B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1672678A (en) * | 2004-05-03 | 2005-09-28 | 深圳微芯生物科技有限责任公司 | Separation and extraction of natural active long-chain fatty acid component for preventing and treating prostatosis and the prepn and application of its medicine prepn |
| CN1857361A (en) * | 2006-03-17 | 2006-11-08 | 崔彬 | Medicine for treating prostatosis and its preparing method and application |
Non-Patent Citations (1)
| Title |
|---|
| 韩慧英.前列康及其原料油菜花粉(Brassica napus L. pollen)活性成分的研究.《中国优秀硕士学位论文全文数据库(医药卫生科技辑)》.2007,摘要,说明书12,16,89页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101569618B (en) | 2011-11-09 |
| CN102512405A (en) | 2012-06-27 |
| CN101569618A (en) | 2009-11-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102512405B (en) | One class long-chain fatty acid derivative or the plant extract containing it are preparing the application in the medicine suppressing activity of aromatizing enzyme | |
| CN101879156B (en) | Medicinal composition and application thereof | |
| CN101856346B (en) | Medical application of coumaroyl spermidine type compounds or plant extracts thereof | |
| CN102512412B (en) | One class fatty glyceride suppresses the application in the medicine of activity of aromatizing enzyme in preparation | |
| CN101570485B (en) | Sugar alcohol ester of long-chain fatty acid, separation and extraction method thereof and application thereof in inhibiting the activity of aromatizing enzyme | |
| CN105884720A (en) | Buspirone hydrochloride pharmaceutical composition and medical application thereof | |
| CN101569630B (en) | Application of steroid compounds or plant extracts containing same in preventing and treating prostatoplasia diseases | |
| CN101570481B (en) | Polyhydroxy long-chain fatty acid, separation and extraction method thereof and application thereof in inhibiting the activity of aromatizing enzyme | |
| CN105012294B (en) | New application of the ellagic acid compounds in treatment antihyperuricemic disease drug is prepared | |
| CN105801541A (en) | Pharmaceutical composition of amoxicillin and medical application of pharmaceutical composition | |
| CN111297847B (en) | Application of amomum kravanh extract in preparation of alpha-glucosidase inhibitor medicine | |
| CN110772596B (en) | Compound Chinese medicine peach blossom extract and its preparation process and use as medicine for treating diabetic cardiomyopathy | |
| CN108785316A (en) | Purposes of the cortex periplocae C21 steroids in preparing IDO inhibitor | |
| CN1857337B (en) | Use of patrinia herb and its extract in preparing medicine for treating prostatic hyperplasia | |
| CN108785322A (en) | Purposes of the Heiguteng exract C21 steroids in preparing IDO inhibitor | |
| CN101570560B (en) | Two sterol derivatives, separation and extraction method thereof and application thereof in preventing and treating prostatoplasia diseases | |
| CN105232605A (en) | Traditional Chinese medicine compound treating prostatic hyperplasia and preparation and application thereof | |
| CN110279732A (en) | Application of the Fructus Chebulae extract in the food, drug or health care product that preparation inhibits amylase and glucosidase activity | |
| CN111228253B (en) | Application of amomum kravanh extract in preparation of alpha-glucosidase inhibitor medicine | |
| CN113754624B (en) | Compound in alpinia zerumbet, extraction, separation and purification method and application thereof | |
| CN115025141B (en) | White dorsum Shemu total saponins and preparation method and application thereof | |
| CN108785321A (en) | Purposes of the Heiguteng exract C21 steroids in preparing IDO inhibitor | |
| CN106478556A (en) | A kind of pharmaceutical composition of Lofexidine Hydrochloride and its medical usage | |
| CN108785317A (en) | Purposes of the cortex periplocae C21 steroids in preparing IDO inhibitor | |
| CN106146604A (en) | The pharmaceutical composition of a kind of dihydralazine sulfate and medical usage thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20161019 Address after: 222001 Jiangsu city of Lianyungang Province Economic and Technological Development Zone Jiangning industrial city Kanion Road No. 58 Patentee after: Kangyuan Pharmceutical Co., Ltd. Patentee after: Shanghai Institute of pharmaceutical industry Address before: 200040 Beijing West Road, Shanghai, No. 1320, No. Patentee before: Shanghai Institute of pharmaceutical industry |