CN100493507C - Application of compound 6-furfuryl amino purine in preparing medicine for treating female genital organ damage - Google Patents
Application of compound 6-furfuryl amino purine in preparing medicine for treating female genital organ damage Download PDFInfo
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- 239000003814 drug Substances 0.000 title claims abstract description 9
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- 229960001669 kinetin Drugs 0.000 title abstract 5
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of a compound 6-furfuryl amino purine (commonly known as kinetin) in preparing a medicine for resisting female reproductive organ injury. Experiments prove that the compound 6-furfuryl aminopurine can locally improve the capability of ovary and uterus in resisting oxidative damage, improve the estrogen content of organisms and play a certain anti-aging role on the organisms. The 6-furfuryl amino purine as one kind of exogenous purine matter has phytohormone-like effect, and is favorable to resisting outer oxidation damage of mouse, promoting the synthesis of antioxidant enzyme, and trapping and eliminating free radical directly to inhibit oxygen radical reaction and lipid peroxidation and maintain the integrity of cell membrane.
Description
Technical field
The present invention relates to the new purposes of chemical compound 6-furfuryl group amidopurin, be specifically related to the application that chemical compound 6-furfuryl group amidopurin is used to prepare anti-female genital organ damage medicine, experimentation through the applicant proves that chemical compound 6-furfuryl group amidopurin can improve the oxidation resistance in ovary and uterus to animal body under the oxidative damage state.
Background technology
Ovary is the basic of women, this is not only because all internal feature (uterus of women, fallopian tube etc.) and surface (mammary gland, skin etc.) all support by ovary, the more important thing is that nearly 500 places tissue and the necessary estrogen of organ are all by ovarian secretion in women's body.Ovary is breed life basic, and major function is ovulation and secretion women estrogen; Keep menstrual cycle, reproductive function and femaleness.Can be described as the cradle that breeds life, controlling women's youth, beauty, health and old and feeble.
Oxygen-derived free radicals is the one of the main reasons that causes animal body aging and disease.Though an amount of oxygen-derived free radicals and the balance between the antioxidant system has important function for the function of keeping ovary and uterus in the body, but, can cause the balance between active oxygen and the antioxidant system to get muddled along with body aging or some extrinsic factor such as smoking.Total antioxidant capacity descends in the excessive rising of oxygen-derived free radicals, follicular fluid, causes ovarian function to descend, even senilism.The excessive generation that can also cause endometriosis of oxygen-derived free radicals, therefore, too high oxygen-derived free radicals may be the reason that some reproductive system aspect disease takes place in the body.
Modern medicine thinks that the hormonal system of human body is made up of multiple endocrine gland, and wherein gonadal hormone is to keeping the functional activity of human body, and delaying human body caducity plays important regulatory role.After the women entered the middle age, ovary began to enter the naturally-aged atrophy along with the increase at age, deterioration, the state that estrogen secretion reduces.In the time can not bringing into play inhibitory action to hypothalamus-pituitary hormone, the incretion balance mechanism beginning of whole hypothalamus-hypophysis-gonad (ovary) axle system is disorderly, and then cause whole body changed by the histoorgan generation degeneration such as internal organs, skeleton, blood vessel, skin of estrogen control, become the principal element that Women disease and senile chronic disease take place.Therefore, the female reproductive organ's that causes because of oxygen-derived free radicals of prevention aging and pathological change have very important significance.
Chemical compound 6-furfuryl group amidopurin is that Mliller in 1956 finds in the herring sperm dna extract that heat sterilization is crossed a kind ofly has an active micromolecular compound of the cell division of promotion.It is a kind of non-natural basic element of cell division, is commonly called as kinetins, molecular formula C
10H
9N
5O.Pure product are white solid, and fusing point is 265-266 ℃, are amphoteric compound.Be soluble in dilute hydrochloric acid or dilute alkaline soln; Be insoluble in water, ethanol, ether and acetone.The structural formula of its 6-bran amidopurin is as follows:
6-bran amidopurin is that first is found the material with basic element of cell division effect.Except that having the effect that promotes cell division, differentiation and growth, also has the organ senescence of delaying, the induced bud differentiation, increase stomatal aperture, callus induction sprouts, and removes apical dominance, break the lateral bud dormancy and promote germination, delay protein and chlorophyllous Degradation.Be mainly used in tissue culture, promote cell division and regulate cell differentiation, slow down aging, preserving fruit and vegetable utilizing is regulated the transportation of nutrient substance, promotes aspects such as solid.
Antioxidation and the antidotal effect of 6-furfuryl group amidopurin on plant is very tangible, and the research aspect animal and human's body defying age also seldom yet there are no report to the influence of animal and human's body ovary and uterus oxidation resistance.
Summary of the invention
The objective of the invention is to, the application that amidopurin is used to prepare anti-female genital organ damage medicine of chemical compound 6-furfuryl group is provided, a large amount of evidences through the applicant, chemical compound 6-furfuryl group amidopurin has the effect of anti-oxidative damage to animal and human's body ovary and uterus, and the anti-oxidative damage of having found 6-furfuryl group amidopurin first acts on animal and human's body equally also to have.
Chemical compound 6-furfuryl group amidopurin is expected to be applied to treating by oxygen-derived free radicals directly and the premature ovarian failure that causes indirectly and endometriosis, functional disorder etc., is applied to the exploitation that female antibiosis is grown old and feeble medicine of system and health product.As make powder, pill, tablet, injection, electuary, unguentum, nano-emulsion, capsule or oral liquid.Administering mode is oral administration, drug administration by injection and transdermal administration, and consumption is limited in the 450mg/kg.b.w.
The specific embodiment
Female genital organ damage of the present invention is ovary oxidative damage or uterus oxidative damage.
Described ovary oxidative damage is the premature ovarian failure that is caused by extraneous galactose and self disorders of galactose metabolism; Or ovarian function decline, senilism, reproductive performance that smoking causes descend; Or ovarian dysfunction, estrogen secretion disorder, reproductive performance descend; Or the oocyte growth is impaired and the genotoxicity damage.
Described uterus oxidative damage is the damage that endometriosis or spontaneous abortion disease cause.
Described ovary oxidative damage and uterus oxidative damage also comprise by trinitrotoluene, carbon tetrachloride, chloronaphthalene, acrylic aldehyde, arsenic, hydrargyrum, antimony, aniline, chloroform, dimethyl formamide, nitrophenols, acetaldehyde, organophosphor, propylene is fine or plumbous chemical substance causes necrocytosis, ovarian cancer and the cervical cancer of ovary and uterus of varying degrees.
The concrete test example that provides below in conjunction with the inventor further specifies the new purposes that chemical compound 6-furfuryl group amidopurin of the present invention is used to improve female reproductive organ's oxidation resistance.
1 material
1.1 test drug and reagent
6-furfuryl group amidopurin: purchase in the Xiamen star is grand and reach the chemical reagent company limited, produce by U.S. Sanland company.Be mixed with the storing solution of 1500mg/L, 3000mg/L with the hydrochloric acid of 0.1mol/L, standby.Malonaldehyde (MDA) detection kit, bio-engineering research institute, lot number: 20051208 are built up in Nanjing; Glutathione peroxidase (GSH-Px) detection kit, bio-engineering research institute, lot number: 20051214 are built up in Nanjing; Superoxide dismutase (SOD) detection kit, bio-engineering research institute, lot number: 20051212 are built up in Nanjing; The bovine serum albumin standard substance, Roche; Estradiol radioimmunity test kit, Tianjin Jiuding Medical Biological Engineering Co., Ltd, lot number: RG6609
1.2 key instrument
UV1102 type ultra-violet and visible spectrophotometer, Shanghai Techcomp Instrument Ltd. makes; The sub very much electronic balance of BS224S, Beijing Sai Duolisi instrument system company limited; HS10268 type 10～100 μ l pipettors, DRAGONMED company produces; The TD24-WS low speed autobalancing centrifuge, Hunan, Changsha instrument centrifuge instrument company limited; FJ-2008P γ radioimmunity enumerator, Xi'an 262 factories.
1.3 experimental animal and damage model duplicate
A cleaning level KM mice, female, body weight (25 ± 3) g, available from Xi-an No.4 Military Medical Univ.'s Experimental Animal Center, the quality certification number: SCXK (army) 2002-006.
6-furfuryl group amidopurin gastric infusion, dosage is calculated according to mg/Kg.b.w, once a day, continuous 35 days.
2 methods
2.1 grouping
Mice is divided into 4 groups immediately, specifically is grouped as follows:
A group: injecting normal saline under the blank group, every day butt, injected continuously 45 days, irritate stomach 0.1mol/L hydrochloric acid 0.5ml, once a day, continuous 35 days, last was irritated the fasting of stomach animal.
B group: injection of d-galactose (200mg/kg) under the D-galactose model group, every day butt, injected continuously 45 days, duplicate mice aging model.Inject and rose in the 10th day, irritate stomach 0.1mol/L hydrochloric acid 0.5ml, once a day, continuous 35 days, animal fasting behind the last filling stomach.
C group: 6-furfuryl group amidopurin low dosage protection group: injection of d-galactose (200mg/kg) under the every day butt, injected continuously 45 days, duplicate mice aging model.Inject and rose in the 10th day, irritate stomach 1500g/LKT medicinal liquid 0.5ml, dosage is 30mg/Kg.b.w, once a day, continuous 35 days, animal fasting behind the last filling stomach.
D group: 6-furfuryl group amidopurin high dose protection group: injection of d-galactose (200mg/kg) under the every day butt, injected continuously 45 days, duplicate mice aging model.Inject and rose in the 10th day, irritate stomach 3000g/LKT medicinal liquid 0.5ml, dosage is 60mg/Kg.b.w, once a day, continuous 35 days, animal fasting behind the last filling stomach.
2.2 sample to be tested collection
After the fasting 12 hours, measure mice and oestrus period, mice is put to death in the eyeball blood sampling when mice is in dioestrus.Get whole ovary tissues and part uterine cancer cell, centrifugal with the tissue homogenate of making 1% and 5% after the cold saline rinsing, get supernatant, prepare to detect every index; Hematology lab's relaxing the bowels with purgatives of warm nature of gathering leaves standstill 2h, gets serum, carries out estradiol and measures.
2.3 the mensuration of total protein.
The requirement of by specification before measuring antioxidase and MDA, is measured the total protein content of 5% ovary and uterus homogenate earlier.With the Coomassie brilliant blue method, the preparation standard curve is measured at 540nm with ultraviolet-uisible spectrophotometer respectively and is respectively managed the A value, calculates the protein content of each pipe according to standard curve.
2.4 SOD measures in ovary and the uterus homogenate
Get 1% ovary and uterus homogenate, require to operate respectively according to test kit, with ultra-violet and visible spectrophotometer 550nm place colorimetric (distilled water returns to zero, the 1cm cuvette).Calculate the SOD unit of activity according to following formula:
2.5 ovary and uterus homogenate MDA Determination on content
Get 5% ovary and uterus homogenate respectively, require operation according to test kit, with ultra-violet and visible spectrophotometer 532nm place colorimetric (distilled water returns to zero, the 1cm cuvette).Calculate MDA content according to following formula:
2.6 ovary and the active mensuration of uterus homogenate GSH-Px
Get 1% liver homogenate, require operation according to test kit, with ultra-violet and visible spectrophotometer 240nm place colorimetric (distilled water returns to zero, the 1cm cuvette).Calculate the GSH-Px enzyme activity according to following formula:
2.7 serum estradiol Determination on content
Get 100 μ L mice serums, require operation, measure with γ radioimmunity enumerator according to test kit.
3 results
3.1 the measurement result of ovary homogenate SOD vigor
As shown in Table 1, B group (model group) content significantly is lower than A group (normal group) (P＜0.05), only be 86% of A group, the SOD content of C group (low concentration group) and D group (high concentration group) significantly increases, and is about 1.4 times (P＜0.01) and 1.2 times (P＜0.05) of B group (model group) respectively.
Table 1 is respectively organized (the X ± S) of SOD vigor in the ovary homogenate
| Group | Quantity (only) | SOD enzyme activity (U. μ gprot -1) |
| A | 7 | 1.396±0.113 * |
| B | 7 | 1.206±0.239 |
| C | 7 | 1.651±0.153 ** |
| D | 7 | 1.450±0.098 * |
Annotate:
*Compare P＜0.01 with model group,
*Compare P＜0.05 with model group
3.2 MDA Determination on content result in the ovary homogenate
As shown in Table 2, B group (model group) MDA content significantly increases, and has reached 4.8 times more than (P＜0.01) of A group (normal group).C group (low concentration group) is compared with B group (model group) with D group (high concentration group), and the content of MDA is reduced to 23% (P＜0.01) and 36% (P＜0.01) of B group (model group) respectively.
Table 2 is respectively organized (the X ± S) of MDA content situation in the ovary homogenate
| Group | Quantity (only) | MDA content (nmol. μ gprot-1) |
| A | 7 | 0.183±0.017 ** |
| B | 7 | 0.894±0.052 |
| C | 7 | 0.211±0.046 ** |
| D | 7 | 0.322±0.077 ** |
Annotate:
*Compare P＜0.01 with model group;
*Compare P＜0.05 with model group
3.3 the testing result of GSH-Px vigor in the ovary homogenate
Show in the table 3 that B group (model group) is only organized 85% (P＜0.01) of (normal group) for A.C group (low concentration group) and D group (high concentration group) GSH-Px content significantly increase, and are respectively 1.4 times (P＜0.01) and 1.3 times (P＜0.01) of B group.
Table 3 is respectively organized (the X ± S) of GSH-Px vigor situation in the ovary homogenate
| Group | Quantity (only) | GSH-PX content (U. μ gprot -1) |
| A | 7 | 0.0063±0.0004 ** |
| B | 7 | 0.0054±0.0003 |
| C | 7 | 0.0073±0.0005 ** |
| D | 7 | 0.0068±0.0004 ** |
Annotate:
*Compare P＜0.01 with model group;
*Compare P＜0.05 with model group
3.4 the measurement result of uterus homogenate SOD vigor
As shown in Table 4, B group (model group) content significantly is lower than A group (normal group) (P＜0.05), only is 75% of A group (normal group).The SOD content of C group (low concentration group) and D group (high concentration group) significantly increases, and is about 1.2 times (P＜0.05) and 1.3 times (P＜0.05) of B group (model group) respectively.
Table 4 is respectively organized (the X ± S) of SOD vigor in the homogenate of uterus
| Group | Quantity (only) | SOD enzyme activity (U. μ gprot -1) |
| A | 7 | 6.791±0.860 * |
| B | 7 | 5.099±0.582 |
| C | 7 | 6.350±0.432 * |
| D | 7 | 6.782±0.306 * |
Annotate:
*Compare P＜0.01 with model group,
*Compare P＜0.05 with model group
3.5 MDA Determination on content result in the homogenate of uterus
As shown in Table 5, B group (model group) MDA content approximately is 3.2 times (P＜0.01) of A group (normal group).C group (low concentration group) is compared with B group (model group) with D group (high concentration group), and the content of MDA reduces by 28% (P＜0.01) and 37% (P＜0.01) respectively, and compares there was no significant difference with A group (normal group) MDA content.
Table 5 is respectively organized (the X ± S) of MDA content situation in the homogenate of uterus
| Group | Quantity (only) | MDA content (nmol. μ gprot -1) |
| A | 7 | 0.113±0.014 ** |
| B | 7 | 0.357±0.048 |
| C | 7 | 0.103±0.022 ** |
| D | 7 | 0.134±0.035 ** |
Annotate:
*Compare P＜0.01 with model group;
*Compare P＜0.05 with model group
3.6 the testing result of GSH-Px vigor in the homogenate of uterus
As shown in Table 6, B group (model group) is only organized 47% (P＜0.01) of (normal group) for A.C group (low concentration group) and D group (high concentration group) GSH-Px content significantly increase, and are respectively 2.7 times (P＜0.01) and 2.3 times (P＜0.01) of B group (model group).
Table 6 is respectively organized (the X ± S) of GSH-Px vigor situation in the homogenate of uterus
| Group | Quantity (only) | GSH-PX content (U. μ gprot -1) |
| A | 7 | 0.0038±0.0095 ** |
| B | 7 | 0.0018±0.0048 |
| C | 7 | 0.0049±0.0012 ** |
| D | 7 | 0.0041±0.0045 ** |
Annotate:
*Compare P＜0.01 with model group;
*Compare P＜0.05 with model group
3.7 the testing result of serum estradiol content
By in the table as can be seen, B group (model group) mice serum estradiol content significantly descends (P＜0.01), is 21.5% of A group (normal group).After having taken corn plumelet extract, serum estradiol content can access certain lifting.The content of C group (low concentration group) and D group (high concentration group) is respectively 2.01 times (P＜0.05) and 2.00 times (P＜0.05) of B group (model group), has significant difference.
Table 7 is respectively organized serum estradiol content situation (X ± S)
| Group | Quantity (only) | Estradiol content (pmol.L -1) |
| A | 3 | 15.51±1.35 ** |
| B | 3 | 3.33±0.89 |
| C | 3 | 6.68±0.66 * |
| D | 3 | 6.66±0.56 * |
Annotate:
*Compare P＜0.01 with model group;
*Compare P＜0.05 with model group
4 conclusions
Experimental result shows that the female reproductive organ SOD reduction that 6-furfuryl group amidopurin causes the D-galactose, GSH-Px reduction, MDA raise inhibited, and serum estradiol content is had certain effect of keeping.The every index of 6-furfuryl group amidopurin group is compared with model group all has significant difference (P＜0.05), and some has utmost point significant difference (P＜0.01).Can prove that by this experiment 6-furfuryl group amidopurin has the effect of the female mice genitals senescense and damnification that anti-D-galactose causes.
Claims (2)
1, chemical compound 6-furfuryl group amidopurin is used to prepare the application of anti-female reproductive organ's oxidative damage medicine, and described female reproductive organ's oxidative damage is to be caused by disorders of galactose metabolism.
2, application as claimed in claim 1 is characterized in that, described medicine is made powder, pill, tablet, injection, electuary, unguentum, nano-emulsion, capsule or oral liquid.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5164394A (en) * | 1989-06-08 | 1992-11-17 | Senetek, Plc | Method for treating hyperproliferative skin diseases |
| CN1068033A (en) * | 1991-05-16 | 1993-01-20 | 塞尼泰克,Plc | Be used to improve the method and the compositions of adverse effects of aging |
| CN1646113A (en) * | 2002-05-06 | 2005-07-27 | 金伯利-克拉克环球有限公司 | Cell proliferating agents |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5164394A (en) * | 1989-06-08 | 1992-11-17 | Senetek, Plc | Method for treating hyperproliferative skin diseases |
| CN1068033A (en) * | 1991-05-16 | 1993-01-20 | 塞尼泰克,Plc | Be used to improve the method and the compositions of adverse effects of aging |
| CN1646113A (en) * | 2002-05-06 | 2005-07-27 | 金伯利-克拉克环球有限公司 | Cell proliferating agents |
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