CN103623167A - Use of saw palmetto berry extract in preparation of erectile dysfunction treatment drugs - Google Patents
Use of saw palmetto berry extract in preparation of erectile dysfunction treatment drugs Download PDFInfo
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- CN103623167A CN103623167A CN201210309278.8A CN201210309278A CN103623167A CN 103623167 A CN103623167 A CN 103623167A CN 201210309278 A CN201210309278 A CN 201210309278A CN 103623167 A CN103623167 A CN 103623167A
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Abstract
The invention belongs to the field of traditional Chinese medicines, and relates to a use of a saw palmetto berry extract in the preparation of erectile dysfunction treatment drugs. The saw palmetto berry extract is processed to prepare a softgel, and after male rats and rabbits are continuously intragastrically administrated with the saw palmetto berry extract softgel preparation for a week, a biological signal processing system is used to determine the smooth muscle discharge amplitude of the corpus spongiosum of the above electrically-stimulated experiment animals; and experiment results show that the saw palmetto berry extract softgel can inhibit the hydrolysis of cGMP and improve the concentration of the cGMP by inhibiting the activity of PDE5 in the corpus spongiosum in order to realize the dosage-dependent enhancement of the discharge amplitude of the corpus spongiosum of the electrically-stimulated experiment animals. The above effects and mechanism are similar to that of silaenafil drugs. The saw palmetto berry extract softgel preparation can be used as an erectile dysfunction treatment drug, and has a substantial effect.
Description
Technical field
The invention belongs to the field of Chinese medicines, relate to the pharmaceutical usage of Chinese medicine saw palmetto fruit extract, be specifically related to the purposes of saw palmetto fruit extract in preparation treatment erectile dysfunction drug.
Background technology:
Erectile Dysfunction (Erectile Dysfunction, ED) claim again sexual impotence (Impotence), refers to that adult male does not have enough erections to complete whole sexual intercourse processes; Owing to being subject to for a long time the constraint of feudal ideology, this disease does not arouse enough attention always.Described ED is the disease that sickness rate is higher, and not only the physical and mental health of adult male in serious harm, also to social development, produces significant impact.Abroad, more generally acknowledged data are that male's aging research in Massachusetts shows at present: 40～70 years old male's ED prevalence is 52.0 ± 1.3%, wherein light, in, the prevalence of severe ED is respectively 17.2%, 25.2% and 9.6%, have dysbolismus as cardiovascular patient and diabetics between good sending out; In Chinese Shanghai, 1582 40 years old above city men, find that ED prevalence is about 73% by inquiry.Have predictive display, by 2025, global ED patient will arrive 300,000,000 populations.
At present, generally believe that the contraction diastole obstacle of the cavernous body of penis smooth muscle that the generation of ED and second message,second messenger's conducting system of the cyclic guanosine monophosphate on cavernous body of penis (cyclic guanosine monophosphate, cGMP) are leading is relevant.Described specific phosphodiesterase enzyme 5(phosphodiesterase type5, PDE5) inhibitor sldenafil (viagra), tadanafil be to treat clinically line oral drugs various, various cause of disease ED at present; Its activity that suppresses PDE5 by selectivity suppresses the hydrolysis of cGMP, thereby promotes and extend the activation time-histories of cGMP, the persistent period of prolonged erection.Yet investigation shows approximately has 30%ED patient because of to the reactionless drug withdrawal of PDE5 inhibitor.
Saw palmetto fruit extract (saw palmatto extract, SPE) employing derives from the short saw palmetto fruit extraction of the U.S. and forms, and wherein contains multiple complex composition, is conventionally made into soft capsule.Described sabal berry is traditional the using and the medicine for the treatment of genitourinary system of American Indians, for alleviating mucosa irritation symptom, increase testicular function or increasing mammary gland size; As far back as just there being medical literature 19th century, report that it is used for the treatment of benign prostatic hyperplasia (benign prostatic hyperplasia, BPH) and the lower urethral symptom that has a strong impact on middle-aging male quality of life that causes comprises frequent micturition, urgent micturition, nocturia, urine retention, weak stream of urine etc.At present, received two kinds of methods for the treatment of BPH are 5 alpha reductase inhibitors and alpha adrenergic receptor blocker, can be alone or share; Yet above-mentioned Therapeutic Method tends to cause sexual dysfunction.Have research disclosedly to have the clinical testing data to patient BPH of contrast to show, SPE improve aspect maximum urine stream, less nocturia suitable with typical treatment BPH medicine finasteride; In many European countries, SPE is one of diseases of urinary system prescription medical herbs that the most frequently used treatment BPH is relevant.Also discovery of research simultaneously, SPE untoward reaction occurs less relatively, and slight, and the incidence rate of ED is well below the BPH patient of application finasteride.Zlotta etc. adopt questionnaire form to Permixon(sabal fatty acid sterin extract), Tamsulosin (alpha-2-adrenoceptor blocker) and finasteride (5α-reductase inhibitor) treatment BPH patient's sexual function is evaluated, result of study shows, with respect to Tamsulosin and finasteride, sexual function is had a negative impact, Permixon to the quality of the interest of male sexuality, erection, come to orgasm and the aspect male's sexual such as ejaculation has no adverse effects.
The mechanism of action of relevant saw palmetto fruit extract is still not clear, and research infers that it may be relevant with inhibition 5 alpha-reductase activity, anti-androgenic effect, adjusting hero, oestrogen balance, alpha receptor blocking effect, inhibition prostata tissue growth factor activity, anti-proliferative effect and antiinflammatory action etc.So far, there is not yet relevant saw palmetto fruit and extract the bibliographical information that can treat ED.
Summary of the invention
The object of this invention is to provide the pharmaceutical usage that Chinese medicine saw palmetto fruit extract is new, be specifically related to the purposes of saw palmetto fruit extract in preparation treatment erectile dysfunction drug.The soft capsule of soft capsule
In the present invention, described Chinese medicine saw palmetto fruit extract is made soft capsule, can be by the commercial acquisition of advancing by leaps and bounds.
The present invention confirms that by whole animal model test described Chinese medicine saw palmetto fruit extract (saw palmatto extract, SPE) soft capsule has the effect for the treatment of very significantly erection disturbance;
The present invention also adopts continuous circulation to determine the active molecular mechanism of further analyzing the soft capsule treatment erection disturbance of described Chinese medicine saw palmetto fruit extract of PDE5 in phosphorus colorimetric method for determining animal corpus cavernosum tissue.
Particularly, the present invention verifies that by following experiment described saw palmetto fruit extract (soft capsule) has the effect for the treatment of very significantly erection disturbance:
(1) the continuous gavage of soft-capsule of saw palmetto fruit extract impact on the amplitude of discharging after the electricity irritation of rat cavernous body of penis after a week
SPE soft capsule (purchased from German Taide pharmaceutical factory), laboratory animal adopts 40 of SD male rats, body weight 280-300g, (purchased from Fudan University's medical experiment animal center);
Rat is divided into 4 groups, is respectively dosage group and SPE high dose group in matched group, SPE low dose group, SPE, and SPE adopts normal saline preparation, every day gastric infusion once, administration capacity is 1mL/100g body weight, successive administration 7 days; After last gastric infusion 24h, both sides, rat penis back are connected into SMUP-E bio signal processor (Fudan University's shanghai Medicine institute physiology and pathophysiology system supervise), give square-wave pulse electricity irritation, record gives the discharge scenario of spongy body smooth muscle after electricity irritation
Result demonstration, when electricity irritation, SD male rat cavernous body of penis electric discharge amplitude obviously increases with respect to the rat of normal saline group, and is dose dependent; Show that SPE effectively increases rat cavernous body of penis pressure after electricity irritation, has good therapeutical effect to ED;
(2) the continuous gavage of soft-capsule of saw palmetto fruit extract impact on the amplitude of discharging after the electricity irritation of rabbit cavernous body of penis after a week
SPE soft capsule (purchased from German Taide pharmaceutical factory),
30 of male new zealand rabbits, average weight 2.0 – 2.5kg, purchased from Fudan University's medical experiment animal center;
Rabbit adaptability is raised after 10 days and is started to test; 30 rabbit are divided into normal saline matched group at random, SPE soft capsule low dose group, middle dosage group, high dose group, every group of 6-7 is only; SPE adopts normal saline preparation, every day gastric infusion once, administration capacity is 1mL/kg body weight, successive administration 7 days; After last gastric infusion 24h, measure rabbit spongy body electric discharge amplitude after electricity irritation;
Result shows, after continuous 7 days give SPE, there is the result similar to above-mentioned rat experiment in male rabbit, with respect to normal saline group, the rabbit cavernous body of penis electric discharge amplitude that gives various dose SPE is significantly increased, be dose-dependence, show that SPE can effectively increase rabbit cavernous body of penis pressure after electricity irritation, has good therapeutical effect to ED;
(3) the continuous gavage of soft-capsule of saw palmetto fruit extract impact on rat and rabbit cavernous body of penis PDE5 activity after a week
After the electric discharge of rat in above-mentioned test 1 and 2 and rabbit cavernous body of penis is measured and finished, routine is isolated laboratory animal corpus cavernosum tissue sample, with PBS solution, cleans and weighs that to be placed in-70 ℃ of Refrigerator stores standby;
During experiment, laboratory animal corpus cavernosum tissue sample is put in the taper centrifuge tube of pre-cooling, after cleaning, moved into liquid nitrogen cryopreservation pipe, liquid nitrogen container spends the night; Within 3rd, take out, pulverize and be organized into Powderedly, put into taper centrifuge tube; In powder sample, add the powerful whirlpool concussion of lysate 30s, put afterwards ice groove into and hatch 30min, repeatedly centrifugal after powerful vortex concussion, pipette supernatant to new aseptic centrifuge tube, pipette 20 μ l and carry out protein quantification by BCA method, all the other samples are placed in-70 ℃ of preservations;
Adopt GENMEDPDE5 enzymatic activity continuous circulation to determine the mensuration that phosphorus colorimetric determination detection kit (GENMED SCIENTIFICSINC.U.S.A, the agency of Shanghai Jie Mei gene Pharmaceutical Technology Co., Ltd) is carried out enzymatic activity; Substrate cyclic nucleotide (cAMP or cGMP), in the situation that PDE5 sensitivity inhibitor (MY-5445) exists, by the catalytic action of PDE5, the reaction that is hydrolyzed, produces after 1-guanosine 5-monophosphate product, via 5-nucleotidase (5-nucleotidase, 5-NT) effect, discharge free phosphorus acid group, so with peacock green dyestuff generation chromogenic reaction after, by spectrophotometer (660nm wavelength), measure the variation of its peak value; The size of absorbance and PDE5 enzymatic activity are directly proportional;
First bioassay standard curve, then carries out sample background (not adding enzymatic liquid and substrate solution) and measures, and obtains the non-specific activity of sample;
Described sample gross activity and non-specific active calculating by following formula:
{ [obtaining the active corresponding 5-GMP concentration (μ mol/L) of sample-obtain the corresponding 5-GMP concentration (μ mol/L) of sample background according to standard curve according to standard curve] the X diluted sample multiple } 30 (response time of ÷; Min)=nmol5-GMP ml min ÷ sample protein concentration (mg ml)=nmol5-GMP mg min;
Sample specific activity calculates by following formula:
The non-specific activity of sample specific activity=sample gross activity-sample;
Result shows, through gavage, gives the decline that the active relative physiologic saline of PDE5 group in the rat corpus cavernosum tissue of various dose SPE has significance; Through gavage, give PDE5 activity in the rabbit corpus cavernosum tissue of SPE of various dose and also occurred similar result; Experimental result shows that SPE can suppress the activity of PDE5 in cavernous body of penis effectively, thereby suppresses the hydrolysis of cGMP, extends the time-histories of erection, and ED is played to good therapeutical effect.
Above-mentioned experimental result shows, SPE soft capsule of the present invention is by suppressing PDE5 activity in cavernous body of penis, thereby suppress the hydrolysis of cGMP, improve cGMP concentration, thereby after making laboratory animal electricity irritation, cavernous body of penis electric discharge amplitude is dose dependent enhancing, above-mentioned effects anb Mechanism and sldenafil are similar, and described SPE soft capsule has significant therapeutic effect to erection disturbance.
For the ease of understanding, below will to the present invention, be described in detail by the specific embodiment.It needs to be noted, these descriptions are only exemplary descriptions, do not form limitation of the scope of the invention.According to the discussion of this description, many variations of the present invention, change are all apparent concerning one of ordinary skill in the art.
Accompanying drawing explanation
Fig. 1 shown the continuous gavage of soft-capsule of saw palmetto fruit extract after one week on the impact of the amplitude of discharging after rat and the electricity irritation of rabbit cavernous body of penis (mean ± standard error, n=6-10),
Wherein,
A: the continuous gavage of soft-capsule of saw palmetto fruit extract is the impact on the amplitude of discharging after the electricity irritation of rat cavernous body of penis after one week;
B: the continuous gavage of soft-capsule of saw palmetto fruit extract is the impact on the amplitude of discharging after the electricity irritation of rabbit cavernous body of penis after one week;
Compare * P<0.05, * * P<0.01 with saline group;
With the comparison of SPE small dose group, Δ Δ P<0.01;
With dosage group comparison in SPE, ##P<0.01.
Fig. 2 shown the continuous gavage of soft-capsule of saw palmetto fruit extract after one week on the impact of rat and rabbit cavernous body of penis PDE5 activity (mean ± standard error, n=4-7),
Wherein,
A: the continuous gavage of soft-capsule of saw palmetto fruit extract impact on rat cavernous body of penis PDE5 activity after a week;
B: the continuous gavage of soft-capsule of saw palmetto fruit extract impact on rabbit cavernous body of penis PDE5 activity after a week;
Compare * P<0.05, * * P<0.01 with saline group;
With the comparison of SPE small dose group, Δ Δ P<0.01;
With dosage group comparison in SPE, ##P<0.01.
The specific embodiment
Embodiment 1
SPE soft capsule (purchased from German Taide pharmaceutical factory),
Laboratory animal adopts 40 of SD male rats, and body weight 280-300g, purchased from Fudan University's medical experiment animal center;
Rat feeding is at 12h light and shade environment, and room temperature is controlled at 22 ℃, ad lib drinking-water; Adaptability is raised after 10 days and is started to test; 40 SD male rats are divided into 4 groups, every group 10, respectively dosage group (28.58mg/kg) and SPE high dose group (57.16mg/kg) in matched group (normal saline), SPE low dose group (14.29mg/kg), SPE, SPE adopts normal saline preparation, every day gastric infusion once, administration capacity is 1mL/100g body weight, successive administration 7 days; After last gastric infusion 24h, adopt 50mg/kg pentobarbital sodium intraperitoneal injection of anesthesia, rat dorsal position is fixed, get two needle electrodes and insert both sides, rat penis back, be connected into SMUP-E bio signal processor (Fudan University's shanghai Medicine institute physiology and pathophysiology system supervise), give 1.2V, frequency is 30Hz, ripple is wide is the square-wave pulse electricity irritation of 0.1ms, continues 30s at every turn; To rat penis back spongy body root, insert the discharge scenario that leading electrode record gives spongy body smooth muscle after cavernosal nerve electricity irritation; Separately get a ground electrode and clamp skin.
As shown in Figure 1A, after the continuous gavage of SPE 7 days, when electricity irritation, SD male rat cavernous body of penis electric discharge amplitude obviously increases with respect to the rat of normal saline group result, and is dose dependent; Show that SPE can effectively increase rat cavernous body of penis pressure after electricity irritation, has good therapeutical effect to ED.
Embodiment 2
SPE soft capsule (SPE) is provided by German Taide pharmaceutical factory.30 of male new zealand rabbits, average weight 2.0 – 2.5kg, purchased from Fudan University's medical experiment animal center; Rabbit is raised at 12h light and shade environment, and room temperature is controlled at 22 ℃, ad lib drinking-water; Adaptability is raised after 10 days and is started to test; 30 rabbit are divided into normal saline matched group at random, SPE soft capsule low dose group (7.5mg/kg), middle dosage group (15mg/kg), high dose group (30mg/kg), every group of 6-7 is only; SPE adopts normal saline preparation, every day gastric infusion once, administration capacity is 1mL/kg body weight, successive administration 7 days; After last gastric infusion 24h, measure rabbit spongy body electric discharge amplitude after electricity irritation.
Result as shown in Figure 1B, after continuous 7 days give SPE, also there is the result similar to rat experiment in male rabbit, with respect to normal saline group, the rabbit cavernous body of penis electric discharge amplitude that gives various dose SPE is significantly increased, also be dose-dependence, wherein low dose of SPE has showed the effect that the cavernous body of penis electric discharge amplitude of sening as an envoy to strengthens; Show that SPE can effectively increase rabbit cavernous body of penis pressure after electricity irritation, has good therapeutical effect to ED.
Embodiment 3
In above-described embodiment 1 and embodiment 2, after rat and rabbit cavernous body of penis electric discharge determination experiment finish, dissect rapidly, isolate corpus cavernosum tissue, comprise and dispel skin, Glans penis, cavernous body of urethra, fascia etc., with 0.01mol/LPBS solution rinse clean blood and weigh after to be placed in rapidly-70 ℃ of Refrigerator stores standby;
During experiment, rat and rabbit corpus cavernosum tissue are put in the taper centrifuge tube of pre-cooling, added to clear up after liquid cleans to be moved in liquid nitrogen cryopreservation pipe, at once put liquid nitrogen container into and spend the night; Within 3rd, from liquid nitrogen container, take out, with grinding rod, pulverize and be organized into Powderedly immediately, put a 15mL taper centrifuge tube into; After adding lysate in sample powder, powerful whirlpool shakes 30s, put afterwards ice groove into and hatch 30min, the 30s of the powerful vortex concussion of every 10min during this time, after in 4 ℃ of centrifugal 10min of desk centrifuge, speed is 10000g, pipette supernatant to new aseptic centrifuge tube, pipette 20 μ l and adopt BCA method to carry out protein quantification, all the other samples are placed in-70 ℃ of preservations;
Adopt GENMED PDE 5 enzymatic activity continuous circulations to determine the mensuration that phosphorus colorimetric determination detection kit (GENMED SCIENTIFICS INC.U.S.A, the agency of Shanghai Jie Mei gene Pharmaceutical Technology Co., Ltd) is carried out enzymatic activity; Substrate cyclic nucleotide (cAMP or cGMP), in the situation that PDE5 sensitivity inhibitor (MY-5445) exists, by the catalytic action of PDE5, the reaction that is hydrolyzed, produces after 1-guanosine 5-monophosphate product, via 5-nucleotidase (5-nucleotidase, 5-NT) effect, discharge free phosphorus acid group, so with peacock green dyestuff generation chromogenic reaction after, by spectrophotometer (660nm wavelength), measure the variation of its peak value; The size of absorbance and PDE5 enzymatic activity are directly proportional;
First bioassay standard curve, then carry out sample background (not adding enzymatic liquid and substrate solution) and measure, in cuvette, add buffer and 5 μ l testing samples, add successively negative fluid, stop buffer and nitrite ion, after static 15min, put spectrophotometer measurement sample background into; Separately get new cuvette, add enzymatic liquid and substrate solution, 30 ℃ add testing sample 5 μ l after hatching 30min, again hatch 30min for 30 ℃.Add successively after the standing 15min of negative fluid, stop buffer and nitrite ion, put into spectrophotometer and detect, obtain sample gross activity; Separately get new cuvette, once add buffer, enzymatic liquid, substrate solution and obligate liquid, after hatching 30min in 30 ℃, add testing sample 5 μ l, 30 ℃ add the standing 15min of negative fluid, stop buffer and nitrite ion after hatching 30min again, put into spectrophotometer and detect, obtain the non-specific activity of sample.
Sample gross activity and non-specific active calculating:
{ [obtaining the active corresponding 5-GMP concentration (μ mol/L) of sample-obtain the corresponding 5-GMP concentration (μ mol/L) of sample background according to standard curve according to standard curve] the X diluted sample multiple } 30 (response time of ÷; Min)=nmol5-GMP ml min ÷ sample protein concentration (mg ml)=nmol5-GMP mg min;
Sample specific activity calculates: the non-specific activity of sample specific activity=sample gross activity-sample;
Result as shown in Figure 2, through gavage, give the decline that the active relative physiologic saline of PDE5 group in the rat corpus cavernosum tissue of various dose SPE has significance, through gavage, give PDE5 activity in the rabbit corpus cavernosum tissue of SPE of various dose and also occurred similar result; Show that SPE can suppress the activity of PDE5 in cavernous body of penis effectively, thereby suppress the hydrolysis of cGMP, extend the time-histories of erection, ED is played to good therapeutical effect.
Claims (4)
1. saw palmetto fruit extract is treated the purposes in erectile dysfunction drug in preparation.
2. by purposes claimed in claim 1, it is characterized in that, described saw palmetto fruit extract is made soft capsule.
3. by purposes claimed in claim 2, it is active that described soft-capsule of saw palmetto fruit extract is used for suppressing cavernous body of penis PDE5, suppresses the hydrolysis of cGMP, improves cGMP concentration.
4. by purposes claimed in claim 2, it is characterized in that, the dosage of soft-capsule of saw palmetto fruit extract is,
SD male rat: low dose group 14.29mg/kg, middle dosage group 28.58mg/kg, high dose group 57.16mg/kg;
Male new zealand rabbit: low dose group 7.5mg/kg, middle dosage group 15mg/kg, high dose group 30mg/kg.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002051426A2 (en) * | 2000-12-22 | 2002-07-04 | A Glenn Braswell | Compositions and methods for treating sexual dysfunction, enhancing sexual function, increasing testosterone levels, and improving muscle strength and mass |
| WO2009097512A1 (en) * | 2008-02-01 | 2009-08-06 | Innovative Drug Discovery Inc. | Herbal pharmaceutical compositions to treat inflammation and inflammation associated conditions and diseases |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002051426A2 (en) * | 2000-12-22 | 2002-07-04 | A Glenn Braswell | Compositions and methods for treating sexual dysfunction, enhancing sexual function, increasing testosterone levels, and improving muscle strength and mass |
| WO2009097512A1 (en) * | 2008-02-01 | 2009-08-06 | Innovative Drug Discovery Inc. | Herbal pharmaceutical compositions to treat inflammation and inflammation associated conditions and diseases |
Non-Patent Citations (2)
| Title |
|---|
| 李明超等: "勃起功能障碍的药物治疗进展", 《医药导报》 * |
| 贾敏如: "《国际传统药物和天然药物》", 31 October 2006, 中国中医药出版社 * |
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Application publication date: 20140312 |