CN102526015A - Application of 3-(3,4-dihydroxycinnamoyl) quinic acid to preparation of medicines or food for preventing and treating ovulation disorder - Google Patents
Application of 3-(3,4-dihydroxycinnamoyl) quinic acid to preparation of medicines or food for preventing and treating ovulation disorder Download PDFInfo
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- CN102526015A CN102526015A CN2012100315765A CN201210031576A CN102526015A CN 102526015 A CN102526015 A CN 102526015A CN 2012100315765 A CN2012100315765 A CN 2012100315765A CN 201210031576 A CN201210031576 A CN 201210031576A CN 102526015 A CN102526015 A CN 102526015A
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Abstract
The invention relates to application of 3-(3,4-dihydroxycinnamoyl) quinic acid to the preparation of medicines and functional food for protecting an ovarian function, promoting ovulation and treating ovulation disorder. The 3-(3,4-dihydroxycinnamoyl) quinic acid can be prepared into medicinal preparations of various forms which comprise oral administration, injection and pulmonary inhalation preparations and transdermal preparations and particularly comprise injections, oral liquid, tablets, capsules, granules, aerosols, powder aerosols, pressurized sprays, patches and the like.
Description
Technical field:
The invention belongs to technical field of pharmaceuticals, particularly, relate to chlorogenic acid, promote ovulation, the medicine or the Application in Food of treatment ovulation failure at preparation protection ovary.
Technical background:
Ovulation failure is called does not again ovulate, and is a principal element that causes sterility and infertility, accounts for 25～30% of female acyesis factor.Along with working strength strengthens, the increasing of stress, the deterioration of environment and unsound life style, the sickness rate of ovulation failure is in continuous rising.Ovulation failure except cause infertile, also can cause symptoms such as menoxenia, amenorrhea, hirsutism, obesity.In addition, owing to do not ovulate for a long time, sex hormone metabolism is disorderly, endometrium hyperplasia and acyclic progestogen antagonism is prone to bring out carcinoma of endometrium, breast carcinoma etc.Therefore, reply ovulation failure patient gives and enough attention, carries out positive therapeutic.
Follicular development and ovulation are by the regulation and control of HPO gonad axis, and any one position of gonad axis all can cause ovulation failure unusually.The hypothalamic function obstacle accounts for 38% in ovulation failure, and disease of pituitary gland accounts for 17%, and ovarian dysfunction accounts for about 45%.At present, the treatment to ovulation failure is mainly drug ovulation.The medicine of one line comprises estrogen, clomiphene, and Ta Moqianfen, menotropins for inj, short follicle generates element and gonadotropin releasing hormone.The basic role of these medicines all is to promote ovulation through the regulation process of participating in the HPG hormone; All has side effect; Can not life-time service, so these medicines all can not fundamentally treat ovulation failure, it is imperative that searching can prevent and treat the new drug of ovulation failure.
Chinese medicine is the rarity of Chinese traditional culture, is the whole mankind's wealth.Along with the continuous development of modern medicine technology, the application of Chinese medicine and research break out the vitality that makes new advances again.Modernization exploitation to Chinese medicine especially plant amedica mainly is to utilize modern science and technology from plant amedica, to extract effective site and monomer chemical constituent.Exploitation has the protection ovarian function from plant amedica, promotes ovulation, and the medicine of treatment ovulation failure has wide society and economic benefit prospect.
Chlorogenic acid distributes in plant extensively, all has to pteridophyta from high dicotyledon, and higher plant has in the leaf of Chinese medicine Flos Lonicerae, the Cortex Eucommiae content.Its product is respectively Flos Lonicerae extract, Cortex Eucommiae extract.Chlorogenic acid has wide biological activity, and does not see that the green former human body of getting it right has the report of any adverse side effect at present, is a kind of Chinese medicine ingredients that has very much potentiality to be exploited therefore.Up to now, do not see in the prior art that chlorogenic acid possesses the protection ovary, promote ovulation, the report of treatment ovulation failure.
Summary of the invention:
The present invention is based on chlorogenic acid and can improve the egg laying amount of model organism nematicide; The mechanism that shortens ovulatory cycle and increase the mice litter size; In its promoting ovulation drug or food that further is applied to; Purpose aims to provide the new purposes of medicine food of chlorogenic acid, and its medicine or Application in Food in preparation treatment ovulation failure and protection ovarian function is provided.
In order to realize above-mentioned purpose of the present invention, the invention provides following technical scheme:
The application of chlorogenic acid in the medicine of preparation treatment ovulation failure.
In the above-mentioned application, ovulation failure is a not ruptured follicle syndrome of luteinization.
In the above-mentioned application, ovulation failure is a polycystic ovary syndrome.
In the above-mentioned application, ovulation failure is a premature ovarian failure.
The present invention provides chlorogenic acid in preparation protection ovarian function Application in Food simultaneously.
The present invention also provides the application of chlorogenic acid in the medicine of preparation protection ovary.
The present invention also provides the application of chlorogenic acid in the functional food of preparation control ovulation failure.
The present invention also provides the application of chlorogenic acid in preparation protection ovarian function medicine.
Chlorogenic acid of the present invention (3-(3,4-Dihydroxycinnamoyl) quinic Acid), its molecular characterization is:
When chlorogenic acid of the present invention is used as medicine, can directly use, perhaps use with the form of pharmaceutical composition.This pharmaceutical composition contains 0.1-99%, is preferably the chlorogenic acid of 0.5-90%, and all the other are pharmaceutically acceptable, to human body and nontoxic and inert pharmaceutically suitable carrier of animal and/or excipient.
Described pharmaceutical carrier or excipient are that one or more are selected from solid, semisolid and liquid diluent, extra-fill material and pharmaceutical preparation adjuvant.Pharmaceutical composition of the present invention is used with the form of per weight dose.The method that the compositions of chlorogenic acid adopts pharmacy and field of food to generally acknowledge is prepared into various dosage forms, like liquid preparation (injection, suspensoid, Emulsion, solution, syrup etc.), solid preparation (tablet, capsule, granule, electuary etc.), spray, aerosol etc.Medicine of the present invention can carry out the control of ovary obstacle through route of administration such as injection (intravenous injection, intravenous drip, intramuscular injection, lumbar injection, subcutaneous injection) and oral, sublingual administration, mucosa dialysis.
Description of drawings:
Fig. 1 chlorogenic acid is to the nematicide average larva number of every day in the egg-laying season;
Every nematode larval number of Fig. 2;
Fig. 3 nematicide ovulatory cycle;
Fig. 4 ICR mice two cell stage quantity;
Fig. 5 ICR mice blastaea hatchability;
Fig. 6 newborn mice quantity;
Fig. 7 newborn mice body weight.
The specific embodiment:
Below in conjunction with accompanying drawing, further essentiality content of the present invention is described with embodiments of the invention, but content of the present invention is not limited thereto.
Embodiment 1:
Chlorogenic acid adds the injection water by routine, fine straining, and injection is processed in the embedding sterilization.
Embodiment 2:
Chlorogenic acid is dissolved in the sterile water for injection, and stirring makes molten, filters with aseptic suction funnel, and aseptic again fine straining is sub-packed in 2 ampoules, and the sterilization sealing by fusing gets injectable powder behind the frozen drying.
Embodiment 3:
In chlorogenic acid and excipient weight ratio is that 9: 1 ratio adds excipient, processes powder.
Embodiment 4:
In chlorogenic acid and excipient weight ratio is 1: 5-1: 10 ratio adds excipient, pelletizing press sheet.
Embodiment 5:
Chlorogenic acid is processed oral liquid by conventional oral liquid method for making.
Embodiment 6:
In chlorogenic acid and excipient weight ratio is that 5: 1 ratio adds excipient, processes capsule or granule or electuary.
Embodiment 7:
In chlorogenic acid and excipient weight ratio is that 3: 1 ratio adds excipient, processes capsule or granule or electuary.
Embodiment 8:
Press chlorogenic acid 46.6 grams, add starch 600 grams, lactose 200 grams, menthol 3 grams, carboxymethyl starch sodium 152 grams are processed buccal tablet, as functional food.
Essence for a better understanding of the present invention, the pharmacological action result with the Test Example of the present invention pharmaceutical composition that to be chlorogenic acid form with pharmaceutical carrier and/or excipient explains superiority of the present invention below, but does not limit the present invention with this.
Test Example 1:
Chlorogenic acid promotes the activity test of ovulation in nematicide:
(Caenorhabditis elegans C.elegans) experimentizes as model, and this chemical compound is at 20 ℃, and the administration concentration of 0.05mM (mM) and 0.5mM can increase the egg laying amount of nematicide, shortens the oviposition period of nematicide with beautiful nematicide.The result shows that chlorogenic acid has the function that promotes the nematicide ovulation.
Experiment material:
The beautiful nematicide N2 of wild type: available from U.S. nematicide heredity center (CGC);
Chlorogenic acid (3-(3,4-Dihydroxycinnamoyl) quinic Acid): available from Switzerland Adamas Reagent company.
Experimental program:
1, nematicide recovery, synchronization:
(1) from-80 ℃ of refrigerators, takes out frozen N2 nematicide (CGC, the U.S.) 1-2 pipe, be placed in the super-clean bench, thawed naturally about 5 minutes.
(2) draw supernatant cryopreserving liquid in the centrifuge tube, remain about 0.5ml, note changing the rifle head, can not cause cross-contamination.
(3) inhale dozen sedimentary nematicide gently with pipettor, make suspension, after all drawing, transfer on NGM+OP50 (escherichia coli mutant) flat board and cultivate.
(4) under aseptic wind condition, dry up residual liquid on the flat board, about 10-15 minute.
(5) cover the culture dish lid after, be placed on 20 ℃ of temperature, cultivate in the incubator of humidity 60%.
(6) waste liquid of sucking-off and rifle head are all put into beaker, after experiment finishes, add the processing of part hypochloric acid water and outwell after 2 hours.
(7) recovery is cultivated after about 50 hours, takes out, and microscopically when there is 80-100 ovum 35 times of haplopia Yezhong, can carry out synchronization.
(8) ddH
2O 8ml washes each flat board.
(9) the about 7.5ml eluent of each dull and stereotyped collection is transferred to eluent in the 15ml centrifuge tube.
(10) take by weighing 10gNaOH, be dissolved in the 50ml sterilized water, be made into 5N NaOH, 5N NaOH/ sodium hypochlorite is made into the 4.5ml mixed liquor according to 1.5/3, and mixing is subsequent use.
(11) in the 15ml centrifuge tube, add the above-mentioned mixed liquor of 3.5ml, shook up 1 time in per 2 minutes, till the residual body of Guan Zhongwu nematicide.
(12) 1300g is centrifugal 1 minute.
(13) remove supernatant, add sterile deionized water 3ml, mixing.
(14) 1300g is centrifugal 1 minute.
(15) remove supernatant, resuspended with 1ml M9, the collection liquid behind the mixing is transferred in the 50ml centrifuge tube that contains 25-35ml M9 approximately, 20 ℃, overnight incubation under humidity 60% condition.
(16) the centrifugal collection of 1300g L1 phase synchronization nematicide is transferred to the synchronization nematicide of collecting on the 90mm NGM flat board and to cultivate, and 20 ℃, cultivates under humidity 60% condition.
2, contain dull and stereotyped preparation of chemical compound and culture of nematodes:
(1) 200ml solid NGM, microwave oven melts, and in the time of below 65 ℃, adds following composition:
1M MgSO
4200 μ l, 5mg/ml Chol est erol 200 μ l, 1M CaCl
2200 μ l, 5ml KPO
4(108.3g KH
2PO
4, 35.6g K
2HPO
4, H
2O to 1 liter) pH6,4mM fudr 200 μ l, the NGM culture medium when adding 65 ℃ below in the ratio of each final concentration the chlorogenic acid mother solution, mix homogeneously restricts 10 diameter 9cm Tissue Culture Plates.After unnecessary flat board sealed, it was subsequent use to put 4 ℃ of preservations.
(2) at the OP50 bacterium liquid of the dull and stereotyped upper berth system deactivation of NGM, aseptic wind is done.
(3) nematicide in each working plate picking 60-80 bar L4 later stage, each testing compound are done two and repeat flat board, 20 ℃ of cultivations.
3, ovulation experiment:
(1) material preparation and nematicide adult are handled the same.
(2) the synchronization nematicide adult of cultivating is transferred on contrast, 0.05mM chlorogenic acid, the 0.5mM chlorogenic acid flat board 20 ℃ of cultivations.
(3) shift adult every day in new culture dish, old culture dish continue to be cultivated in 20 ℃, hatches the larva number in each culture dish of technology to larva.
(4) repeating step (3) is no longer laid eggs until adult.
Experimental result: chlorogenic acid (0.05mM, 0.5mM) the ovulation situation of every nematicide after 20 ℃ of processing.The result shows that chlorogenic acid increases the ovulation amount at nematicide ovulation initial stage significance, and shortens ovulatory cycle (seeing table 1):
Table 1 chlorogenic acid is to the influence of nematicide ovulation situation
Can draw following result from accompanying drawing:
As a result 1: (result shows that chlorogenic acid increases the ovulation amount at nematicide ovulation initial stage significance, and shortens ovulatory cycle to chlorogenic acid for 0.05mM, 0.5mM) the average larva number of every nematicide every day in first day to the 6th day egg-laying season after 20 ℃ of processing.
As a result 2: chlorogenic acid (0.05mM, 0.5mM) the average larva number of every nematicide after 20 ℃ of processing; The result shows that the chlorogenic acid significance increases total egg laying amount of every nematicide.Chlorogenic acid has the function that promotes the nematicide fertility.
As a result 3: chlorogenic acid (0.05mM, 0.5mM) the average egg-laying season of every nematicide after 20 ℃ of processing.The result shows that the chlorogenic acid significance shortens the ovulatory cycle of nematicide.
Test Example 2:
Chlorogenic acid promotes the activity test of ovulation in mice:
Experimentize as model with the ICR mice.The result shows that chlorogenic acid has the function that promotes the ovulation of ICR mice.
Laboratory animal adopts the ICR mice, 6 ages in week, and body weight 21-29g, the large Science and Technology Ltd. that reaches provides by Chengdu.Tried thing chlorogenic acid (3-(3,4-Dihydroxyc innamoyl) quinic Acid): available from Switzerland Adamas Reagent company.
Experiment one:
Chlorogenic acid promotes the effect of ovulation:
Experimental procedure:
1. the injection of chlorogenic acid:
The preparation of chlorogenic acid injection (dosage 13.7mg/kg.Configuration concentration 2mg/ml).
Experimental mice injection chlorogenic acid, matched group injecting normal saline 200ul.
Weighing every day mice body weight is according to mice body weight injection chlorogenic acid injection.
2. female Mus and male Mus mate cultivation.
3. observe the cloudy bolt formation of the female Mus situation that mates every day.The female Mus that has cloudy bolt to form is explained the copulation of ovulating, chooses independent raising.Do not have the female Mus of cloudy bolt to continue to have an injection, continue to mate raising.
4. after cloudy bolt formed 40 hours, disconnected neck was put to death mice.Take out fallopian tube.
5. from fallopian tube, obtain the embryo.
6. the embryo counts.
7. the embryo continues to cultivate 3 days, and counting is hatched the blastaea number.
8. adopt relatively two groups mean of t check.
Experimental result:
The result: after injecting chlorogenic acid (13.7mg/kg) every day, the quantity of ICR mice two cell stages.The result shows that comparing (injecting normal saline 200ul every day) chlorogenic acid significance with matched group increases ICR mice two cell stage numbers.
Table 2ICR mice two cell stage quantity
Behind the injection chlorogenic acid (13.7mg/kg), ICR mice two cell stages continue to be cultured to the quantity of hatching blastaea.The result shows, compares (injecting normal saline 200ul every day) with matched group, two groups the blastaea rate of hatching there was no significant difference.Chlorogenic acid can promote ovulation, but can not reduce embryo's quality.
Table 3ICR mice blastaea hatchability
| Matched group | Experimental group | |
| Mice consumption (only) | 14 | 14 |
| Two cell stages (individual) | 203 | 237 |
| On average hatch blastaea (individual) | 12.57±1.02 | 14.57±1.95 |
| On average hatch the blastaea rate | 0.867±0.04 | 0.86±0.09 |
| The P value | 0.63 |
Experiment two:
The injection of chlorogenic acid is to the influence of newborn mice quantity and body weight:
Experimental procedure:
1. the injection of chlorogenic acid: the preparation of chlorogenic acid injection (dosage 13.7mg/kg.Configuration concentration is: 2mg/ml).
Experimental mice injection chlorogenic acid, the matched group injecting normal saline.
Weighing every day mice body weight is according to mice body weight injection chlorogenic acid injection.
2. female Mus and male Mus mate cultivation.
3. observe the cloudy bolt formation of the female Mus situation that mates every day.The female Mus that has cloudy bolt to form is explained the copulation of ovulating, chooses independent raising.Do not have the female Mus of cloudy bolt to continue to have an injection, continue to mate raising.
4. the single culture mice of copulation is until childbirth.
5. count the also body weight of weighing newborn mice.
6. statistics adopts the t check
Experimental result:
As a result 4: after injecting chlorogenic acid (13.7mg/kg) every day, ICR mice farrowing quantity.The result shows, compares the farrowing quantity that (injecting normal saline 200ul every day) chlorogenic acid significance increases the ICR mice with matched group.
Table 4ICR mice farrowing quantity
As a result 4: behind the injection chlorogenic acid (13.7mg/kg), the body weight of ICR mice newborn mice.The result shows, compares (injecting normal saline 200ul every day) with matched group, two groups newborn mice body weight there was no significant difference.Chlorogenic acid can promote ovulation, but can not reduce the body weight of newborn mice.
Table 5 newborn mice body weight
Claims (7)
1. the application of chlorogenic acid in the medicine of preparation control ovulation failure.
2. according to the application of claim 1, described ovulation failure is a not ruptured follicle syndrome of luteinization.
3. according to the application of claim 1, described ovulation failure is a polycystic ovary syndrome.
4. according to the application of claim 1, described ovulation failure is a premature ovarian failure.
5. the application of chlorogenic acid in the medicine of preparation protection ovary.
6. the application of chlorogenic acid in the functional food of preparation control ovulation failure.
7. chlorogenic acid is in preparation protection ovarian function Application in Food.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102895353A (en) * | 2012-11-09 | 2013-01-30 | 张洪涛 | Chinese herbal medicine for treating cow luteinization dyspoiesis |
| US20140045937A1 (en) * | 2012-08-08 | 2014-02-13 | Oculus Innovative Sciences, Inc. | Methods of treating polycystic ovarian syndrome using chlorogenic acid |
| US9259410B2 (en) | 2014-04-08 | 2016-02-16 | Oculus Innovative Sciences, Inc. | Methods of treating polycystic ovarian syndrome using chlorogenic acid and inositol |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101120937A (en) * | 2006-08-11 | 2008-02-13 | 四川九章生物化工科技发展有限公司 | Application of chlorogenic acid in preparing medicine with cervical cancer preventing and treating efficiency |
| CN101120936A (en) * | 2006-08-11 | 2008-02-13 | 四川九章生物化工科技发展有限公司 | Application of chlorogenic acid in preparing medicine with estrogenic or estrogenic promoting action |
| CN101147733A (en) * | 2006-09-21 | 2008-03-26 | 四川九章生物化工科技发展有限公司 | Application of chlorogenic acid in preparing medicine with treating woman organ tumor function |
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2012
- 2012-02-13 CN CN2012100315765A patent/CN102526015A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101120937A (en) * | 2006-08-11 | 2008-02-13 | 四川九章生物化工科技发展有限公司 | Application of chlorogenic acid in preparing medicine with cervical cancer preventing and treating efficiency |
| CN101120936A (en) * | 2006-08-11 | 2008-02-13 | 四川九章生物化工科技发展有限公司 | Application of chlorogenic acid in preparing medicine with estrogenic or estrogenic promoting action |
| CN101147733A (en) * | 2006-09-21 | 2008-03-26 | 四川九章生物化工科技发展有限公司 | Application of chlorogenic acid in preparing medicine with treating woman organ tumor function |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140045937A1 (en) * | 2012-08-08 | 2014-02-13 | Oculus Innovative Sciences, Inc. | Methods of treating polycystic ovarian syndrome using chlorogenic acid |
| CN102895353A (en) * | 2012-11-09 | 2013-01-30 | 张洪涛 | Chinese herbal medicine for treating cow luteinization dyspoiesis |
| US9259410B2 (en) | 2014-04-08 | 2016-02-16 | Oculus Innovative Sciences, Inc. | Methods of treating polycystic ovarian syndrome using chlorogenic acid and inositol |
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Application publication date: 20120704 |