CN104825522A - Application of safflower extract in preparation of 5 alpha-reductase inhibitors - Google Patents
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Abstract
The invention discloses an application of safflower extract in the preparation of 5 alpha-reductase inhibitors, and belongs to the field of medicine. The safflower extract has a prominent inhibiting effect on 5 alpha-reductase especially I-type 5 alpha-reductase and II-type 5 alpha-reductase; and can effectively prevent testosterone from being converted into dihydrotestosterone so as to prevent the synthesis of male hormone (dihydrotestosterone), so the safflower extract has an important meaning on preventing or treating diseases related with local male hormone metabolic disorder or male hormone actions. Furthermore, the safflower extract is prepared from traditional Chinese herbals, is safer, does not have any side effect, and is more beneficial for the patients' health.
Description
Technical field
The present invention relates to biomedicine field, particularly a kind of Flos Carthami extract is preparing the application in 5α-reductase inhibitor medicaments.
Background technology
5α-reductase (5 α-R) is △ 4,5 reduction of a kind of key enzyme of male hormone metabolism, the various steroid substrate of this enzyme energy catalysis, makes testosterone (T) be converted into the stronger dihydrotestosterone of biological activity (DHT).5α-reductase is positioned the memebrane protein on target cell microsome, thinks that it has three kinds of isozymes at present, i.e. I type 5α-reductase, II type 5α-reductase and III type 5α-reductase.I type 5α-reductase is mainly present in liver and non-genitals's skin, and the optimal pH scope playing physiological action is 6-9; And II type 5α-reductase is mainly present in prostate, testis, epididymis, seminal vesicle and scalp hair follicles, the optimal pH playing physiological action is 5.5; And less to the research of III type 5α-reductase, there is report to think overexpression in its carcinoma of prostate healed at refractory.Research shows; the diseases such as such as prostatic hyperplasia, androgens psilosis (i.e. seborrheic alopecia), acne, polycystic ovarian syndrome, male intersex deformity, female hirsutism are all relevant with local androgen Developmental and Metabolic Disorder or androgenic effect; and 5α-reductase and androgenic metabolism are closely related, so 5α-reductase plays important effect for the expression of above-mentioned disease.
For example, androgens psilosis (androgenic alopecia, AGA), have another name called seborrheic alopecia (Seborrheic alopecia, SA) or the pathogenesis of male pattern alopecia (male pattern alopecia, MPA) be due to Hyperandrogenism or to Androgen-sensitive, its clinical manifestation is that head fat secretion increases, hair attenuates, shorten, and color is thin out etc.Research shows, the generation of seborrheic alopecia and II type 5α-reductase of pilosebaceous unit closely related.Free T can pass through sebocyte cell film and enters substrate sebocyte cell and glandular cell, in cytoplasm 5α-reductase effect under be converted into DHT, then T, DHT are combined with the androgen receptor protein of high-affinity, form androgen receptor conjugate and enter nucleus, activate DNA control centre, regulate sebaceous hyperplasia and function.Its regulation and control sebum secretion produces too much sebum and causes hair greasy, and too much sebum compressing or blocking hair follicle hole, make trichotrophy under-supply.In addition, oleic acid, linoleic acid etc. in sebum secretion thing when excessive to the toxic effect of hair follicle.By hair can be made above to enter resting stage prematurely, and to miniature follicle switches, thus cause seborrheic alopecia.Visible, suppress the activity of II type 5α-reductase to have great importance for prevention and therapy seborrheic alopecia.
In further example, acne is a kind of common pilosebaceous unit chronic inflammation disease, and research shows, local androgen Developmental and Metabolic Disorder is one of its topmost cause of disease.I type 5α-reductase is expressed in all Skin Cells, but expresses at most at acne predilection site sebocyte cell.Free T can pass through sebocyte cell film and enters substrate sebocyte cell, DHT is converted under the effect of I type 5α-reductase, then DHT starches receptor protein with the specific cell of high-affinity and is combined, this androgen receptor compound moves in nucleus, information is reached nucleus, activate DNA control centre, cause biosynthesis and the release of some regulatory factor, thus regulate hypertrophy and the function of sebaceous gland.Therefore, the activity of I type 5α-reductase is suppressed to have great importance for prevention and therapy acne.From the above, a kind of 5α-reductase reductase inhibitor medicaments is provided to have great importance for the treatment disease relevant with local androgen Developmental and Metabolic Disorder or androgenic effect.
5α-reductase inhibitor common is at present mainly the medicine of synthetic, such as finasteride, epristeride, dutasteride etc.But inventor finds, above-mentioned synthetic drug, while effectively suppressing 5α-reductase activity, can cause bad side reaction to human body, such as, male breast womanization, muscle growth can be caused impaired.
Summary of the invention
Embodiment of the present invention technical problem to be solved is, provide a kind of Flos Carthami extract and preparing the application in 5α-reductase inhibitor medicaments, wherein this Flos Carthami extract is safer to human body, and has no side effect.Concrete technical scheme is as follows:
First aspect, embodiments provides a kind of Flos Carthami extract and is preparing the application in 5α-reductase inhibitor medicaments.
Particularly, described 5α-reductase inhibitor medicaments is the Flos Carthami extract of prevention or treatment effective dose.
Second aspect, embodiments provides a kind of pharmaceutical composition being used for the treatment of the disease relevant with androgenic effect, and described pharmaceutical composition comprises the Flos Carthami extract for the treatment of effective dose.
Further, described pharmaceutical composition also comprises and other medicine classes of Flos Carthami extract compatibility and pharmaceutically acceptable carrier and/or adjuvant.
Particularly, the described disease relevant with androgenic effect is seborrheic dermatitis.
Particularly, the described disease relevant with androgenic effect is acne.
Particularly, the described disease relevant with androgenic effect is prostatic hyperplasia.
Particularly, the described disease relevant with androgenic effect is polycystic ovarian syndrome.
Particularly, the described disease relevant with androgenic effect is male intersex deformity.
Particularly, the described disease relevant with androgenic effect is female hirsutism.
The beneficial effect that the technical scheme that the embodiment of the present invention provides is brought is:
Embodiments provide Flos Carthami extract and prepare the application in 5α-reductase inhibitor medicaments; Flos Carthami extract is to 5α-reductase; particularly I type 5α-reductase and II type 5α-reductase have remarkable inhibitory action; it can effectively suppress testosterone to be converted into dihydrotestosterone; and then suppressing the synthesis of androgen dihydrotestosterone, this has great importance for prevention or the treatment disease relevant with local androgen Developmental and Metabolic Disorder or androgenic effect.And Flos Carthami extract is as Chinese medicine ingredients, safer, has no side effect.
Accompanying drawing explanation
In order to be illustrated more clearly in the technical scheme in the embodiment of the present invention, below the accompanying drawing used required in describing embodiment is briefly described, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skill in the art, under the prerequisite not paying creative work, other accompanying drawing can also be obtained according to these accompanying drawings.
Fig. 1 a is the spectrogram of the testosterone solution utilizing chromatograph of liquid to record that the embodiment of the present invention 2 provides;
Fig. 1 b is the spectrogram of the mixed liquor of the 5α-reductase extracting solution utilizing chromatograph of liquid to record, NADPH and the testosterone solution that the embodiment of the present invention 2 provides;
Fig. 2 is that the finasteride that provides of the embodiment of the present invention 3 is to the suppression ratio schematic diagram of 5α-reductase activity.
Detailed description of the invention
Unless otherwise defined, all technical terms that the embodiment of the present invention is used all have the identical implication usually understood with those skilled in the art.Before embodiment of the present invention is described further in detail, provide definition to understanding some terms of the embodiment of the present invention.
(1), in the embodiment of the present invention, described " treatment effective dose " refers to and produces treatment function or activity to human or animal body, and on physiology can the amount that accepts by human or animal.
(2) in the embodiment of the present invention, described " pharmaceutically acceptable carrier and/or adjuvant " refers to and is applicable to human or animal, and without excessive bad side reaction (as toxicity, stimulation and allergy), there is carrier and/or the adjuvant of rational benefit/risk ratio.
For making the object, technical solutions and advantages of the present invention clearly, below in conjunction with accompanying drawing, embodiment of the present invention is described further in detail.
First aspect, embodiments provides a kind of Flos Carthami extract and is preparing the application in 5α-reductase inhibitor medicaments.
Inventor studies discovery; Flos Carthami extract is to 5α-reductase; particularly I type 5α-reductase and II type 5α-reductase have remarkable inhibitory action (proving to obtain by experiment in vitro); it can effectively suppress testosterone to be converted into dihydrotestosterone; and then suppressing the synthesis of androgen dihydrotestosterone, this has great importance for prevention or the treatment disease relevant with local androgen Developmental and Metabolic Disorder or androgenic effect.And Flos Carthami extract is as Chinese medicine ingredients, safer, has no side effect, be more conducive to the health of patient.
As preferably, this 5α-reductase inhibitor medicaments is the Flos Carthami extract of prevention or treatment effective dose.
Second aspect, embodiments provides a kind of pharmaceutical composition being used for the treatment of the disease relevant with androgenic effect, and this pharmaceutical composition is 5α-reductase inhibitor medicaments, that is this pharmaceutical composition comprises the Flos Carthami extract for the treatment of effective dose.
It will be understood by those skilled in the art that, should disease relevant with androgenic effect refer to the pathogeny of this disease and androgenic secretion how much closely related, and being subject to the regulation and control of androgen-level, it comprises the disease caused by local androgen Developmental and Metabolic Disorder.For example, should the disease relevant with androgenic effect can be seborrheic dermatitis, acne, prostatic hyperplasia, polycystic ovarian syndrome, male intersex deformity or female hirsutism.
Further, this pharmaceutical composition also comprises and other medicine classes of Flos Carthami extract compatibility and pharmaceutically acceptable carrier and/or adjuvant.For example, this carrier can be nano-particle, liposome, cholesterol, chitosan etc.This adjuvant can be dextrin etc.
For example, above-mentioned 5α-reductase inhibitor medicaments or the dosage form of each pharmaceutical composition can be selected from solution, suspension agent, dry powder doses, Emulsion, Controlled release formulation or extended release preparation; Its administering mode can be selected from drug administration by injection (such as, intravenous injection, articular cavity local injection or intramuscular injection etc.) or oral administration etc.
Further, Flos Carthami extract described in the embodiment of the present invention has meaning well known in the art, it can be understood as and extracts Flos Carthami, it is made to be mainly water miscible chalcone compounds Carthamus yellow, and not fatty oils Palmic acid, myristic acid, lauric acid, two Palmic acids, oleic acid and linoleic acid, the compositions such as volatile oil, cellulose, protein.
The preparation method of this Flos Carthami extract can be the common extractive technique in this area, for example, can adopt and prepare Flos Carthami extract with the following method:
Get dry flos carthami, the distilled water being equivalent to flos carthami 10 times of quality is adopted to carry out immersion 20-40min to it under room temperature (23-27 DEG C), preferred 30min, then reflux, extract, repeatedly (such as 2 times, 3 inferior), the time of each reflux, extract, is 0.3-1h, preferred 0.5h.Then adopt multilamellar gauze to filter, obtain filtrate, then concentrate filtrate to extractum.Obtained extractum is placed in crucible, then puts into vacuum drying oven together and carry out drying, pulverous Flos Carthami extract can be obtained.
Below further the present invention will be described by specific embodiment.In following specific embodiment, the unreceipted condition person of involved operation, the condition of all conveniently condition or manufacturer's suggestion is carried out.Raw materials used unreceipted production firm and specification person are can by the conventional products of commercial acquisition.
(1) raw material involved by following examples is as follows:
Flos Carthami, overlord (Guangzhou) company limited provides, and is accredited as the dried floral of feverfew Flos Carthami Carthamus tinctorius L. through Traditional Chinese Medicine University Of Guangzhou professor Lai little Ping;
Finasteride, Mo Shadong pharmaceutical Co. Ltd of the U.S.;
Easy-Lowyer protein determination kit, Beijing CoWin Bioscience Co., Ltd., lot number: 2813B;
Testosterone (purity >98%), BR (biological reagent) level, lot number: #TCL201403;
Nicotinamide adenine dinucleotide phosphate tetrasodium salt/β-NADPH (purity 98%), Roche, lot number: 10041939103;
Tris-HCL, Sen Beijia bio tech ltd, Nanjing, lot number: SBJ0055;
PMSF (purity >99%), Guangzhou Qi Yun biotech company, lot number: #KY201211;
DTT (purity >99%), Guangzhou Qi Yun biotech company, lot number: #py200611;
PBS, Li Fei bio tech ltd, Shanghai, lot number: 8113275;
Other chemical reagent are all domestic analytical pure.
(2) instrument involved by following examples is as follows:
Wear peace high performance liquid chromatograph (UVD170U detector, P680 pump, ASI-100 automatic sampler, TCC-1005 column oven);
Beijing enlightening horse Diamonsil TMC18 post (250mm × 4.6mm, 5 μm);
TGL-5-A centrifuge, Town in Shanghai Ting Hua scientific instrument factory;
XXW-80A type vortex mixed instrument, its woods shellfish of Haimen City and instrument manufacturing company limited;
BS110S ten thousand/analytical balance, good vertical (world) company limited in Hong Kong;
DZF-6050 vacuum drying oven, the permanent Science and Technology Ltd. in Shanghai one;
RT-2100C microplate reader, Shenzhen Lei Du company.
(3) laboratory animal involved by following examples is as follows:
Male SD rat 10, SPF level, body weight 180-220g, Traditional Chinese Medicine University Of Guangzhou's Experimental Animal Center provides, the quality certification number: 20130020.
The preparation of embodiment 15 5 alpha-reductases and quantitatively
The preparation of II type 5α-reductase: get male SD rat 10, fasting be can't help dislocating after water spends the night putting to death, and gets rapidly liver and epididymis (stripping fatty tissue), weighs, shred on ice pan, obtain sample.Then add the pre-cooling homogenate being equivalent to sample quality 3 times of quality and carry out homogenate in glass homogenizer.Homogenate system is at 4 DEG C, and with the rotating speed of 3500rpm centrifugal 2 times, each 10min, gets supernatant.Then with the relative centrifugal force 50min of 10000g, again get supernatant, i.e. 5α-reductase extracting solution, namely II type 5α-reductase is comprised (although also comprise other enzyme/protein in 5α-reductase extracting solution in this 5α-reductase extracting solution, but the PH due to homogenate is 5.5, with this understanding, II type 5α-reductase activity is the highest, and other enzymatic activitys are suppressed).In 5α-reductase extracting solution, add a certain amount of glycerol, obtain II type 5α-reductase sample for subsequent use (wherein, in II type 5α-reductase sample for subsequent use, the volumetric concentration of glycerol is 10%), subpackage, is stored in-80 DEG C of ultra cold storage freezers, for subsequent use.
Wherein, the PH that this homogenate is dissolved in 1mol/L by DTT, 1mL glycerol of PMSF, 100uL 100mmol/L of 100uL 100mmol/L is in the Tris-HCL buffer of 5.5, and adds fixed molten the preparation to 10mL of Tris-HCL buffer and obtain.
The preparation of I type 5α-reductase: get male SD rat 20, fasting be can't help dislocating after water spends the night putting to death, and gets liver rapidly, weighs, shred on ice pan, obtain sample.PH except Tris-HCL buffer used is 6.8, and subsequent step is all identical with the step of preparation II type 5α-reductase, finally obtains I type 5α-reductase sample for subsequent use.
Adopt improvement Lowry standard measure to measure the content of 5α-reductase, represent the concentration of 5α-reductase with the content of total protein in enzyme extract, operate and carry out according to Easy-Lowyer protein determination kit description.BSA standard curve is Y=0.1329X+0.0977, R2=0.9932, and in liver, the concentration of I type 5α-reductase is 12.17mg/ml as calculated, and in epididymis, the concentration of II type 5α-reductase is 5.77mg/ml.
The determination of embodiment 2 testosterone chromatographic condition
(1) chromatographic condition determined is as follows:
Chromatographic column: Diamonsil
tMc18 post (250mm × 4.6mm, 5 μm);
Mobile phase: methanol-water (volume ratio is 70:30);
Flow velocity: 1.0mL/min;
Column temperature: room temperature;
Determined wavelength: 242nm;
Sampling volume: 20 μ l.
(2) methodological study:
The mixed liquor of the testosterone solution of the accurate absorption of difference 20 μ l and the 5α-reductase extracting solution of 20 μ l, NADPH and testosterone solution, and by they injection liquid chromatographies, under the chromatographic condition described in (1), carry out spectrogram mensuration.As illustrated in figs. ia and ib, under the chromatographic condition described in (1), testosterone peak all occurs when about 12min, and peak type is symmetrical, better with the separating degree of other components.The chromatographic condition this demonstrated in the present embodiment described in (1) is solid.
Precision takes testosterone sample 36mg, is mixed with methanol the testosterone mother solution that mass concentration is 5mmol/L.By solution stepwise dilution, its mass concentration is made to be followed successively by 1.44 μ g/ml, 7.2 μ g/ml, 14.4 μ g/ml, 28.8 μ g/ml, 115.2 μ g/ml, 230.4 μ g/ml, 460.8 μ g/ml.Then by the chromatographic condition sample introduction described in (1), map to the mass concentration (X) of testosterone mother solution with testosterone peak area (A), draw testosterone standard curve, obtaining testosterone standard curve is A=0.263X-0.4106, R
2=0.9999.Result shows that testosterone is within the scope of 1.44-460.8 μ g/ml be good linear relationship with peak area in its mass concentration.
Get testosterone mother solution, add methanol dilution, obtain the need testing solution that concentration is 100 μm of ol/L.According to the chromatographic condition continuous sample introduction described in (1) 6 times, measure testosterone peak area A value and also calculate testosterone concentration, 6 sample introductions test the testosterone concentration obtained relative standard deviation RSD be 1.01%, show that instrument precision is high, favorable reproducibility.
Get testosterone need testing solution, according to the chromatographic condition described in (1), respectively at sample introduction when 0h, 2h, 6h, 12h, 48h, measure testosterone peak area A value and calculate testosterone concentration, each time point sample introduction above-mentioned test the testosterone concentration obtained relative standard deviation RSD be 1.37%, this shows that testosterone need testing solution is good at 48 hours internal stabilities.
Get testosterone need testing solution 6 parts, respectively according to the sample introduction respectively of the chromatographic condition described in (1), measure testosterone peak area A value and calculate testosterone concentration, utilize above-mentioned 6 parts of testosterone need testing solutions test the testosterone concentration obtained relative standard deviation RSD be 2.11%, this shows that operational approach repeatability that the present embodiment adopts is good.
The foundation of embodiment 35 alpha-reductase inhibitors external model
(1) assay method of 5α-reductase activity
Test sample QC and control tube are set, Tris-HCL buffer, 5α-reductase extracting solution, testosterone, sample, NADPH are added in reaction tube successively, mix homogeneously, obtain 5α-reductase reaction system.Then this reaction system is made to react 30min at 37 DEG C, and 0.5ml is sampled respectively when 0min and 30min, finally add methanol 1mL stopped reaction, vortex 1min, and under the rotating speed of 5000rpm centrifugal 15min, get supernatant, and adopt average pore size to be that the microporous filter membrane of 0.22 μm filters this supernatant, and high performance liquid chromatography detection is carried out to the supernatant after this filtration.Wherein, sample comprises: the distilled water as blank, the finasteride as positive control and the Flos Carthami extract as given the test agent.Inventor after deliberation after, determine that the total amount of above-mentioned reaction system is 1000 μ l, as shown in table 1.
The composition of table 15 5 alpha-reductases reaction system
Be understandable that, the 5α-reductase (extracting solution) described in the embodiment of the present invention can be understood as I type 5α-reductase or II type 5α-reductase.
In order to obtain best enzyme assay response parameter, substrate testosterone concentration, NADPH concentration, enzyme concentration, reaction temperature, response time condition are optimized.The optimum reaction condition recording I type 5α-reductase is: substrate testosterone concentration is 1000umol/L, NADPH concentration is 1mmol/L, and the concentration of 5α-reductase extracting solution is 3mg/ml, and reaction temperature is 37 DEG C, and the response time is 30min.
The optimum reaction condition of II type 5α-reductase is: substrate testosterone is dense is 1mmol/L for spending 1000umol/L, NADPH concentration, and the concentration of 5α-reductase extracting solution is 0.7mg/ml, and reaction temperature is 37 DEG C, and the response time is 30min.
The activity of 5α-reductase is with T umolL
-1/ (mg protein30min) represents.(please refer to Yan Dongmei, Tu Linglan, Li Wenjun etc., the foundation [J] of RP-HPLC method in-vitro screening 5α-reductase inhibitor model. pharmaceutical analysis magazine, 2008,07:1046-1049).
Testosterone concentration measured value * 100% during testosterone conversion ratio %=(testosterone concentration measured value during testosterone concentration measured value-30min during 0min)/0min.
Testosterone inversion quantity * 100% during the reaction system 30min of 5α-reductase maximum inhibition %=(the testosterone inversion quantity during reaction system 30min of the testosterone inversion quantity-inhibiting during reaction system 30min of non-inhibiting)/non-inhibiting.
Wherein, the preparation method of Flos Carthami extract is as follows: get the dry medical material 150g of Flos Carthami, the distilled water immersion 30min of 1500ml is added under room temperature, reflux, extract, 0.5h, 8 layers of filtered through gauze, are evaporated to extractum shape, extractum is placed in crucible, dry in vacuum drying oven, obtain flos carthami powder 27.6g, the response rate is calculated as 18.4% according to formula (1).
Formula (1): the response rate (%)=dry powder amount/raw medicinal herbs amount × 100%
Flos Carthami dried powder is got before experiment, utilize distilled water to make drug solution that concentration is respectively 50mg/ml, 10mg/ml, 2mg/ml and 0.4mg/ml, drug solution is added by after dilution 20 times in above-mentioned reaction system, then the reaction density of Flos Carthami given the test agent be respectively 2.5,0.5,0.1,0.02mg/ml.
(2) finasteride is on the impact of 5α-reductase activity
The finasteride that specificity suppresses II type 5α-reductase activity is added in the reaction system described in the positives control tube of table 1, finasteride concentration is followed successively by 0.02 μm of ol/L, 0.1 μm of ol/L, 0.5 μm of ol/L, 1 μm of ol/L, carry out enzymatic reaction by the assay method of above-mentioned 5α-reductase activity, obtain finasteride to the suppression ratio of 5α-reductase activity and IC
50, and the reliability of this model is evaluated with this.
As shown in Figure 2, finasteride can be active in dose-dependent inhibition 5 alpha-reductase for result, suppression ratio up to 83.67%, its IC
50for 212nmol/L, with document (Mitamura K, Ogasawara C, Shiozawa A, et al.Determination method for steroid 5alpha-reductase activity using liquidchromatography/atmospheric pressure chemical ionization-mass spectrometry [J] .Anal Sci.2005Oct; 21 (10): 1241-1244.) IC of the finasteride reported
50for 237nmol/L is close.This shows that the present embodiment adopts HPLC method to measure the 5α-reductase activity determination method set up and has specificity, and this model is reliable, stable, can be used for the screening of 5α-reductase inhibitor.
(3) Flos Carthami extract is on the impact of I type 5α-reductase and II type 5α-reductase activity
(3.1) Flos Carthami extract is on the impact of I type 5α-reductase activity
Get the Flos Carthami given the test agent solution of variable concentrations respectively, carry out enzymatic reaction by the assay method of above-mentioned 5α-reductase activity, obtain the suppression ratio of Flos Carthami extract to I type 5α-reductase activity, experimental result is in table 2.
Table 2 Flos Carthami extract is on the impact of I type 5α-reductase activity
Note: compare * p<0.05 with matched group, * * P<0.01
As shown in Table 2, compare with not using the blank group of Flos Carthami extract, Flos Carthami extract concentration is in the Flos Carthami extract group of 0.02mg/ml, the activity of I type 5α-reductase, testosterone conversion ratio there are no significant difference (P>0.05), and Flos Carthami extract concentration is in the Flos Carthami extract group of 0.1mg/ml, 0.5mg/ml, 2.5mg/ml, the equal significance of the activity of I type 5α-reductase, testosterone conversion ratio reduces (P<0.05).This illustrates that the Flos Carthami extract of low dosage can not significantly suppress I type 5α-reductase active, and when its external dosage is greater than 0.1mg/ml, then can I type 5α-reductase be suppressed significantly active in pole, and suppression ratio is up to 88.12%.
(3.2) Flos Carthami extract is on the impact of II type 5α-reductase activity
Get the Flos Carthami given the test agent solution of variable concentrations respectively, carry out enzymatic reaction by the assay method of above-mentioned 5α-reductase activity, obtain the suppression ratio of Flos Carthami extract to II type 5α-reductase activity, experimental result is in table 3.
Table 3 Flos Carthami extract is on the impact of II type 5α-reductase activity
Note: compare * p<0.05 with normal group, * * P<0.01
As shown in Table 3, compare with not using the blank group of Flos Carthami extract, Flos Carthami extract concentration is in the Flos Carthami extract group of 0.02mg/ml, the activity of II type 5α-reductase, testosterone conversion ratio there are no significant difference (P>0.05), and Flos Carthami extract concentration is in the Flos Carthami extract group of 0.1mg/ml, 0.5mg/ml, 2.5mg/ml, the equal significance of the activity of II type 5α-reductase, testosterone conversion ratio reduces (P<0.05).This illustrates that the Flos Carthami extract of low dosage can not significantly suppress II type 5α-reductase active, and when its external dosage is greater than 0.1mg/ml, then can II type 5α-reductase be suppressed significantly active in pole, and suppression ratio is up to 61.65%.
From the above, 4 concentration of the Flos Carthami extract set by the present embodiment all can reduce the activity of I type 5α-reductase and II type 5α-reductase, and suppress the conversion ratio of testosterone.And the suppression ratio of the Flos Carthami extract of its middle and high concentration to I type 5α-reductase and II type 5α-reductase activity is the highest.This demonstrate the activity of Flos Carthami extract to I type 5α-reductase and II type 5α-reductase and all there is good inhibitory action and the Flos Carthami extract suppression ratio of high concentration is maximum.
The foregoing is only preferred embodiment of the present invention, not in order to limit the scope of the invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. Flos Carthami extract is preparing the application in 5α-reductase inhibitor medicaments.
2. application according to claim 1, is characterized in that, described 5α-reductase inhibitor medicaments is the Flos Carthami extract of prevention or treatment effective dose.
3. be used for the treatment of a pharmaceutical composition for the disease relevant with androgenic effect, it is characterized in that, described pharmaceutical composition comprises the Flos Carthami extract for the treatment of effective dose.
4. pharmaceutical composition according to claim 3, is characterized in that, described pharmaceutical composition also comprises and other medicine classes of Flos Carthami extract compatibility and pharmaceutically acceptable carrier and/or adjuvant.
5. pharmaceutical composition according to claim 3, is characterized in that, the described disease relevant with androgenic effect is seborrheic dermatitis.
6. pharmaceutical composition according to claim 3, is characterized in that, the described disease relevant with androgenic effect is acne.
7. pharmaceutical composition according to claim 3, is characterized in that, the described disease relevant with androgenic effect is prostatic hyperplasia.
8. pharmaceutical composition according to claim 3, is characterized in that, the described disease relevant with androgenic effect is polycystic ovarian syndrome.
9. pharmaceutical composition according to claim 3, is characterized in that, the described disease relevant with androgenic effect is male intersex deformity.
10. pharmaceutical composition according to claim 3, is characterized in that, the described disease relevant with androgenic effect is female hirsutism.
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|---|---|---|---|---|
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101926810A (en) * | 2009-10-22 | 2010-12-29 | 南京泽朗医药科技有限公司 | Application of carthamin to preparing drug for treating climacteric syndrome |
-
2015
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Non-Patent Citations (5)
| Title |
|---|
| NAPHATSORN KUMAR ET AL.: "5α-reductase inhibition and hair growth promotion of some Thai plants traditionally used for hair treatment", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
| 乔国芬 等: "《药理学》", 30 November 2013, 北京大学医学出版社 * |
| 潘继升 等: "5α-还原酶在相关疾病中的作用", 《医学综述》 * |
| 竺炯等: "面部脂溢性皮炎的相关性因素分析", 《辽宁中医杂志》 * |
| 贾汉卿 等: "红花性激素样作用的观察", 《黑龙江医药科学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111700899A (en) * | 2020-05-08 | 2020-09-25 | 广东华夏友美生物科技有限公司 | Application of safflower yellow in preparation of II-type 5 alpha-reductase inhibitor |
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