The androgenetic alopecia(AGA)is the most prevalent clinical manifestation of hair loss,believed to be associated with excessive dihydrotestosterone(DHT)caused by typeⅡ5α-reductase(5αR2).The utilization of oral fin...The androgenetic alopecia(AGA)is the most prevalent clinical manifestation of hair loss,believed to be associated with excessive dihydrotestosterone(DHT)caused by typeⅡ5α-reductase(5αR2).The utilization of oral finasteride(FNS),which selectively inhibits 5αR2,is frequently constrained by its adverse effects.Topical FNS formulations can mitigate adverse effects but often exhibit limited dermal permeability.Nanocarriers show great potential in augmenting the cutaneous permeation of loaded FNS due to their inherent properties of selective accumulation within the hair follicles(HFs).In this study,hollow mesoporous silica nanoparticles(HMSN)with varying sizes were utilized as the nanocarriers for FNS,following mixing with the Carbopol hydrogel(F@H/Gel)for direct topical application.Specifically,the influence of size on the targeted delivery of FNS to HFs,and its enhanced therapeutic efficacy for the AGA mice model was evaluated.Results showed that the HMSN,with a diameter of approximately 300 nm,exhibited significant enhancement in FNS retention within skin and HFs,as well as remarkably accelerated hair regrowth on an AGA mouse model.In conclusion,this FNS topical formulation has proved to be a viable approach in offering a secure and efficient treatment modality for AGA.展开更多
Objective:To explore the clinical efficacy and safety of Chuzhi Shengfa tablets combined with finasteride in the treatment of male androgenetic alopecia(AGA).Methods:Sixty male patients with androgenetic alopecia admi...Objective:To explore the clinical efficacy and safety of Chuzhi Shengfa tablets combined with finasteride in the treatment of male androgenetic alopecia(AGA).Methods:Sixty male patients with androgenetic alopecia admitted to our Department of Dermatology between January 2022 and January 2024 were randomly divided into two groups,with 30 patients in each group.The control group was treated with finasteride,while the observation group received a combination of Chuzhi Shengfa tablets and finasteride.The clinical efficacy and adverse reactions in both groups were compared.Results:The overall effectiveness rate in the observation group was 93.33%(28/30),significantly higher than the control group’s 73.33%(22/30),with a statistically significant difference(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The combination of Chuzhi Shengfa tablets and finasteride shows good clinical efficacy in treating male androgenetic alopecia.Additionally,Chuzhi Shengfa tablets are convenient to administer and effectively improve efficacy,significantly improving patients’conditions,and demonstrating good clinical application value.展开更多
As a kind of substrate competition type 5α reductase inhibitor,finasteride is a promising medicine used in the clinical treatment of benign prostatic hyperplasia (BPH).In this paper,a new route for the synthesis of...As a kind of substrate competition type 5α reductase inhibitor,finasteride is a promising medicine used in the clinical treatment of benign prostatic hyperplasia (BPH).In this paper,a new route for the synthesis of finasteride from pregnenolone was proposed.Thus,pregnenolone was converted to finasteride in 10 steps,i.e.,ammoniumation,methoxylation,Oppenauer oxidation,hydrolyzation,cleavage of Δ 4 double bond by oxidation,ring closure by ammonia,hydrogenation of Δ 5 double bond,esterification with methanol,dehydrogenation of 1,2 position in A ring and Bodroux reaction.In this route,expensive reagent 2,2 dipyridyl disulfide commonly used in previous literature was avoided.All of the desired compounds were characterized by MS or/and NMR.The overall yield of finasteride was 13.67% based on pregnenolone.展开更多
Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia （BPH） r...Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia （BPH） rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups： C, untreated control rats; C ＋ D, control rats receiving dutasteride; C ＋ F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats （SHRs）; H ＋ D, SHRs treated with dutasteride; and H ＋ F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density （Sv） of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni＇s posttest. Groups C ＋ D and C ＋ F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C ＋ D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H ＋ D and H ＋ F had less smooth muscle Sv than Group H. Group H ＋ D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was ~reater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.展开更多
In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer （PCa） while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remai...In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer （PCa） while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP （PC3） cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERKI/2 were evaluated. In LNCaP （PC3） mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, flbroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERKI/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERKI/2 were noted in the presence of c-Jun-I- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride＇s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.展开更多
The objective of the present research work is to develop a gradient, reversed-phase liquid chromatographic (RP-UPLC) method for the determination of Finasteride in pharmaceutical bulk drugs for assay and its related i...The objective of the present research work is to develop a gradient, reversed-phase liquid chromatographic (RP-UPLC) method for the determination of Finasteride in pharmaceutical bulk drugs for assay and its related impurities. The chromatographic separation was achieved on a Waters ACQUITY UPLC BEH Phenyl Column (150 mm × 2.1 mm, 1.7 μm), The gradient LC method employs solutions A and B as mobile phase. The solution A Contains 2.5 mM ortho phosphoric acid (Buffer) and solution B contains a mixture of acetonitrile and water in the ratio of (90:10 v/v). The flow rate was 0.22 ml/min and the detection wavelength was 210 nm. In the developed UPLC method, the resolution between Finasteride and its potential impurities, namely Imp-1, Imp-2, Imp-3 and Imp-4 was found to be greater than 2.0. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in alkaline medium and oxidative stress conditions. Degradation product formed during oxidative hydrolysis was found to be Imp-1. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP-UPLC method was validated with respect to linearity, accuracy, precision and robustness. The limit of quantification of Imp-1, Imp-2, Imp-3 and Imp-4 were 0.06, 0.06, 0.05 and 0.036% (of analyte concentration, i.e. 0.5 mg/ml) with 1μl injection volume. The developed method was found to be linear in the range of 2.5 - 15 μg/mL with correlation coefficient of 0.999 for assay procedures and found to be linear in the range of 0.05 - 3 μg/mL with correlation coefficient of 0.999 for related impurities.展开更多
Objective: To evaluate variations in sexual and erectile function in subjects taking 1 mg of finasteride for androgenetic alopecia by administering the abridged 5-item version of the International Index of Erectile Fu...Objective: To evaluate variations in sexual and erectile function in subjects taking 1 mg of finasteride for androgenetic alopecia by administering the abridged 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire before and during treatment. Design: In a multicenter study, 186 patientswith androgenetic alopeciawere asked to complete the IIEF-5 regarding the domain of erectile function before (at baseline) and 4 to 6 months after beginning finasteride treatment. The test was self-administered. Setting: The study was conducted in 7 institutional dermatology departments in Italy (Bologna, Rome, Genoa, Cagliari, Milan, Florence, and Bari). Patients: A total of 186 patients with androgenetic alopecia were evaluated before and 4 to 6 months after the initiation of finasteride therapy (1 mg). All patients (age range, 19-43 years; mean age, 28.3 years) were followed up as outpatients. Results: The score on each of the 5 domains of the IIEF-5 did not showany significant change after 4 to 6months of treatment. Conclusions: Our results support the clinical impression that sexual side effects are actually much less common than reported in clinical trials. The sexual function of all patients remained stable during treatment with 1 mg of finasteride.展开更多
The pathogenesis of benign prostatic hyperplasia(BPH)is commonly regarded as androgen-dependent.The first FDA-approved androgen-targeted medication for BPH,finasteride,achieves its therapeutic effect by selectively in...The pathogenesis of benign prostatic hyperplasia(BPH)is commonly regarded as androgen-dependent.The first FDA-approved androgen-targeted medication for BPH,finasteride,achieves its therapeutic effect by selectively inhibiting type II 5-alpha reductase(SRD5A2).This inhibition reduces the androgenic response by attenuating the interaction between dihydrotestosterone and androgen receptor(AR),ultimately leading to a reduction in prostate volume and alleviation of BPH-associated symptoms.However,it is noteworthy that non-response to finasteride may develop in certain BPH patients,1 indicating a potential inadvertent promotion of disease progression by this treatment.Nevertheless,the underlying mechanism remains elusive.Recent researches suggest that it may be associated with alterations within the prostate gland epithelia.2 Therefore,we designed this study to elucidate this phenomenon by employing spatial transcriptomic(ST)and single-cell RNA sequencing(scRNA-seq)(methods were described in Supplementary Materials in detail).Our findings will improve treatment adjustments by enabling a more accurate evaluation of patient's response to finasteride therapy,thus enhancing therapeutic outcomes.展开更多
Screening and confirmation methods of the major urinary metabolite of finasteride–carboxy-finasteride for doping control purpose were developed.Liquid–liquid extraction was adopted for the sample preparation.Analyte...Screening and confirmation methods of the major urinary metabolite of finasteride–carboxy-finasteride for doping control purpose were developed.Liquid–liquid extraction was adopted for the sample preparation.Analytes were detected by positive electrospray ionization in single quadrupole and triple quadrupole mass spectrometer.In the screening method,selected ion monitoring(SIM)mode was used to monitor m/z 403 for carboxy-finasteride.In the confirmation method,product ion mode was used to monitor the precursor ion m/z 403.The limit of detection was below 2 ng/mL for the screening method.Good linearity was obtained in the range 10.0–500.0 ng/mL.The intra-run and inter-run precision calculated from quality control(QC)samples was less than 5.3%.The accuracy as determined from QC samples was within ±6.6%.The screening method was applied for the analysis of excretion samples,allowing the detection of carboxy-finasteride for up to 49 h in urine specimen collected after an oral administration of 5 mg of finasteride.展开更多
Aim: To evaluate possible results with the stimulation use of minoxidil and the strengthening of hair roots with nutritional cyclical supplements, resulting in increased hair regrowth, without the use of anti androgen...Aim: To evaluate possible results with the stimulation use of minoxidil and the strengthening of hair roots with nutritional cyclical supplements, resulting in increased hair regrowth, without the use of anti androgens and enzyme blockers. Methods: This prospective controlled clinical trial compares the current acknowledged form of treatment for hair loss within two controlled groups for both men and women against the use of cyclical nutritional therapy and minoxidil 2%. One hundred patients in each of the 4 groups, a total of 400 patients, were followed for 1 year. The progress was evaluated every 2 months with computerised measurements of hair density, hair calibre, global photography and uniquely designed self-assessment scores. Results: The use of nutritional supplements showed consistent improvements in both treatment groups of men and women against the controlled groups with a correction of hair fall and minimum 18% increased density within 2 months with further improvement to a maximum of 156% over 1 year. Conclusion: Hair loss occurs when weak, sensitive, follicles are affected by multiple causes. Hair regrowth can be achieved consistently and safely by strengthening the hair roots and promoting hair growth without necessarily depending on the use of anti androgens.展开更多
Objective: To explore the effects of aqueous extract from Phthirusa pyrifolia leaves(67 mg/kg body weight for 12 days) on the reproductive function of male Wistar rats through oral administration.Methods: Animals(n = ...Objective: To explore the effects of aqueous extract from Phthirusa pyrifolia leaves(67 mg/kg body weight for 12 days) on the reproductive function of male Wistar rats through oral administration.Methods: Animals(n = 30), aged 13 weeks and weighing(378.5 ± 5.0) g, were housed in a vivarium under controlled environmental conditions [photoperiod of 12 h light/dark,temperature of(23 ± 1)C] and were fed standard rations ad libitum. The experiment ran for 12 days, wherein animals were divided into three groups: negative control(n = 6)received water, positive control(n = 12) with finasteride at a concentration of 1.0 mg/kg;and a test group(n = 12) submitted to aqueous extract. At the end of the experiment, the animals were sacrificed and submitted to analyses.Results: The morphological results of the testes showed that the aqueous extract induced significant changes in the diameter and cross-sectional area of the seminiferous tubules as well as the thickness of the seminiferous epithelium. Furthermore, the extract was able to abruptly decrease testosterone concentrations by about 81.88% in the treated group when compared with the negative control,(47.0 ± 4.8) ng/d L and(255.0 ± 2.0) ng/d L,respectively, and 76.8%,(211.0 ± 8.7) ng/d L, when compared with finasteride. However,the extract causes neither liver damage nor impairment of renal function.Conclusions: These results suggest that the high amounts of flavonoids shown to be in the extract may be responsible for its hepato-protective effects and suggest a possible decrease in the libido and reproduction of rats.展开更多
Objective：To evaluate the efficacy of Bawu Decoction（八物汤,BWD,Palmul-tang in Korean）against benign prostatic hyperplasia（BPH）.Methods：Twenty-four male Wistar rats were divided into 4 groups,with 6 rats in each...Objective：To evaluate the efficacy of Bawu Decoction（八物汤,BWD,Palmul-tang in Korean）against benign prostatic hyperplasia（BPH）.Methods：Twenty-four male Wistar rats were divided into 4 groups,with 6 rats in each group.The 4 study groups included sham-operated group（CON）,BPH model group,finasteride-treated group,and BWD-treated group.All the groups except CON group received a subcutaneous injection of 10 mg/kg of testosterone,while CON group received saline.Finasteride at a dose of 5 mg/kg was administered to the finasteride-treated group for a period of 4 weeks.BWD group received BWD at a dose of 200 mg/kg for 4 weeks.The prostatic weight,prostate weight to body weight ratio,relative prostate weight ratio,serum testosterone and dihydrotestosterone（DHT）level,and histological analysis of prostatic tissue were analyzed.Results：Compared to BPH model group,BWD administration was associated with reductions in prostatic weight,prostate and relative prostate weight ratio weight to body weight ratio（P〈0.05）.The concentration of serum testosterone and DHT were higher in BPH group compared with CON group（P〈0.05）.Administration of finasteride and BWD suppressed the elevation of serum testosterone and DHT levels significantly（both P〈0.05）.In addition,BWD suppressed the growth of prostatic tissue（P〈0.05）.Conclusion：BWD has suppressant effects on development of BPH through inhibition of serum testosterone and DHT.展开更多
Aim:The reason why non-calibrated hair variables poorly estimate scalp hair coverage during hair growth studies was studied.Methods:Hair productivity integrates density,diameter and daily hair growth rate.Cross-sectio...Aim:The reason why non-calibrated hair variables poorly estimate scalp hair coverage during hair growth studies was studied.Methods:Hair productivity integrates density,diameter and daily hair growth rate.Cross-sectional studies have established hair productivity in female and male patients(480 vs.90 controls)with self-evaluation of hair loss,phototrichogram(CE-PTG-EC)and scalp coverage scoring,(SCS).Tracking productivity of individual hair follicular units from longitudinal studies challenged the application of our methods during drug trials.Results:Hair loss means decreased productivity and increased“time to complete coverage”.The hair mass index(HMI)linearly connects productivity with clinical perception of coverage,i.e.,SCS.The ensuing HMI abacus translates independently of gender,age,pattern or severity and unravelled unequal intervals between categories of the Ludwig and Hamilton classifications.With one severity grade shift,time to complete coverage varied from 21-51 days,i.e.,no equality.During longitudinal studies,SCS detected improved productivity,reflecting clinically relevant responses,but remained stable in the absence of significant productivity variations.Follicular unit labelling and individual hair growth tracing showed that reversal of miniaturised hair follicles does not play a major role during drug-induced hair regrowth.The latter reflects re-activation of resting-dormant terminal hair follicles.The recovered productivity would not be possible once hair follicles enter the phase of structural-functional irreversible miniaturisation.Conclusion:Besides pattern identification,density of nanohair and HMI appear as innovative diagnostic approaches.Abrupt transformation(within one cycle)of terminal hair follicles into miniaturised ones and its reversal as the effect of active FDA-approved drugs remain highly improbable.展开更多
基金funded by the National Natural Science Foundation of China Regional Innovation and Development Joint Fund(Sichuan)(No.U21A20417)the National Natural Science Foundation of China(No.31930067)。
文摘The androgenetic alopecia(AGA)is the most prevalent clinical manifestation of hair loss,believed to be associated with excessive dihydrotestosterone(DHT)caused by typeⅡ5α-reductase(5αR2).The utilization of oral finasteride(FNS),which selectively inhibits 5αR2,is frequently constrained by its adverse effects.Topical FNS formulations can mitigate adverse effects but often exhibit limited dermal permeability.Nanocarriers show great potential in augmenting the cutaneous permeation of loaded FNS due to their inherent properties of selective accumulation within the hair follicles(HFs).In this study,hollow mesoporous silica nanoparticles(HMSN)with varying sizes were utilized as the nanocarriers for FNS,following mixing with the Carbopol hydrogel(F@H/Gel)for direct topical application.Specifically,the influence of size on the targeted delivery of FNS to HFs,and its enhanced therapeutic efficacy for the AGA mice model was evaluated.Results showed that the HMSN,with a diameter of approximately 300 nm,exhibited significant enhancement in FNS retention within skin and HFs,as well as remarkably accelerated hair regrowth on an AGA mouse model.In conclusion,this FNS topical formulation has proved to be a viable approach in offering a secure and efficient treatment modality for AGA.
文摘Objective:To explore the clinical efficacy and safety of Chuzhi Shengfa tablets combined with finasteride in the treatment of male androgenetic alopecia(AGA).Methods:Sixty male patients with androgenetic alopecia admitted to our Department of Dermatology between January 2022 and January 2024 were randomly divided into two groups,with 30 patients in each group.The control group was treated with finasteride,while the observation group received a combination of Chuzhi Shengfa tablets and finasteride.The clinical efficacy and adverse reactions in both groups were compared.Results:The overall effectiveness rate in the observation group was 93.33%(28/30),significantly higher than the control group’s 73.33%(22/30),with a statistically significant difference(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The combination of Chuzhi Shengfa tablets and finasteride shows good clinical efficacy in treating male androgenetic alopecia.Additionally,Chuzhi Shengfa tablets are convenient to administer and effectively improve efficacy,significantly improving patients’conditions,and demonstrating good clinical application value.
文摘As a kind of substrate competition type 5α reductase inhibitor,finasteride is a promising medicine used in the clinical treatment of benign prostatic hyperplasia (BPH).In this paper,a new route for the synthesis of finasteride from pregnenolone was proposed.Thus,pregnenolone was converted to finasteride in 10 steps,i.e.,ammoniumation,methoxylation,Oppenauer oxidation,hydrolyzation,cleavage of Δ 4 double bond by oxidation,ring closure by ammonia,hydrogenation of Δ 5 double bond,esterification with methanol,dehydrogenation of 1,2 position in A ring and Bodroux reaction.In this route,expensive reagent 2,2 dipyridyl disulfide commonly used in previous literature was avoided.All of the desired compounds were characterized by MS or/and NMR.The overall yield of finasteride was 13.67% based on pregnenolone.
文摘Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia （BPH） rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups： C, untreated control rats; C ＋ D, control rats receiving dutasteride; C ＋ F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats （SHRs）; H ＋ D, SHRs treated with dutasteride; and H ＋ F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density （Sv） of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni＇s posttest. Groups C ＋ D and C ＋ F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C ＋ D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H ＋ D and H ＋ F had less smooth muscle Sv than Group H. Group H ＋ D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was ~reater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.
文摘In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer （PCa） while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP （PC3） cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERKI/2 were evaluated. In LNCaP （PC3） mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, flbroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERKI/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERKI/2 were noted in the presence of c-Jun-I- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride＇s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.
文摘The objective of the present research work is to develop a gradient, reversed-phase liquid chromatographic (RP-UPLC) method for the determination of Finasteride in pharmaceutical bulk drugs for assay and its related impurities. The chromatographic separation was achieved on a Waters ACQUITY UPLC BEH Phenyl Column (150 mm × 2.1 mm, 1.7 μm), The gradient LC method employs solutions A and B as mobile phase. The solution A Contains 2.5 mM ortho phosphoric acid (Buffer) and solution B contains a mixture of acetonitrile and water in the ratio of (90:10 v/v). The flow rate was 0.22 ml/min and the detection wavelength was 210 nm. In the developed UPLC method, the resolution between Finasteride and its potential impurities, namely Imp-1, Imp-2, Imp-3 and Imp-4 was found to be greater than 2.0. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in alkaline medium and oxidative stress conditions. Degradation product formed during oxidative hydrolysis was found to be Imp-1. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP-UPLC method was validated with respect to linearity, accuracy, precision and robustness. The limit of quantification of Imp-1, Imp-2, Imp-3 and Imp-4 were 0.06, 0.06, 0.05 and 0.036% (of analyte concentration, i.e. 0.5 mg/ml) with 1μl injection volume. The developed method was found to be linear in the range of 2.5 - 15 μg/mL with correlation coefficient of 0.999 for assay procedures and found to be linear in the range of 0.05 - 3 μg/mL with correlation coefficient of 0.999 for related impurities.
文摘Objective: To evaluate variations in sexual and erectile function in subjects taking 1 mg of finasteride for androgenetic alopecia by administering the abridged 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire before and during treatment. Design: In a multicenter study, 186 patientswith androgenetic alopeciawere asked to complete the IIEF-5 regarding the domain of erectile function before (at baseline) and 4 to 6 months after beginning finasteride treatment. The test was self-administered. Setting: The study was conducted in 7 institutional dermatology departments in Italy (Bologna, Rome, Genoa, Cagliari, Milan, Florence, and Bari). Patients: A total of 186 patients with androgenetic alopecia were evaluated before and 4 to 6 months after the initiation of finasteride therapy (1 mg). All patients (age range, 19-43 years; mean age, 28.3 years) were followed up as outpatients. Results: The score on each of the 5 domains of the IIEF-5 did not showany significant change after 4 to 6months of treatment. Conclusions: Our results support the clinical impression that sexual side effects are actually much less common than reported in clinical trials. The sexual function of all patients remained stable during treatment with 1 mg of finasteride.
基金supported by the National Natural Science Foundation of China (No. 62101319)the Qingpu District Health Commission Discipline Talent Project of Shanghai, China (No. YY2023-3, TX2023-4)the Medical Discipline Construction Project of Pudong New Area Health System (Shanghai, China) (No. PYWgf2021-06).
文摘The pathogenesis of benign prostatic hyperplasia(BPH)is commonly regarded as androgen-dependent.The first FDA-approved androgen-targeted medication for BPH,finasteride,achieves its therapeutic effect by selectively inhibiting type II 5-alpha reductase(SRD5A2).This inhibition reduces the androgenic response by attenuating the interaction between dihydrotestosterone and androgen receptor(AR),ultimately leading to a reduction in prostate volume and alleviation of BPH-associated symptoms.However,it is noteworthy that non-response to finasteride may develop in certain BPH patients,1 indicating a potential inadvertent promotion of disease progression by this treatment.Nevertheless,the underlying mechanism remains elusive.Recent researches suggest that it may be associated with alterations within the prostate gland epithelia.2 Therefore,we designed this study to elucidate this phenomenon by employing spatial transcriptomic(ST)and single-cell RNA sequencing(scRNA-seq)(methods were described in Supplementary Materials in detail).Our findings will improve treatment adjustments by enabling a more accurate evaluation of patient's response to finasteride therapy,thus enhancing therapeutic outcomes.
文摘Screening and confirmation methods of the major urinary metabolite of finasteride–carboxy-finasteride for doping control purpose were developed.Liquid–liquid extraction was adopted for the sample preparation.Analytes were detected by positive electrospray ionization in single quadrupole and triple quadrupole mass spectrometer.In the screening method,selected ion monitoring(SIM)mode was used to monitor m/z 403 for carboxy-finasteride.In the confirmation method,product ion mode was used to monitor the precursor ion m/z 403.The limit of detection was below 2 ng/mL for the screening method.Good linearity was obtained in the range 10.0–500.0 ng/mL.The intra-run and inter-run precision calculated from quality control(QC)samples was less than 5.3%.The accuracy as determined from QC samples was within ±6.6%.The screening method was applied for the analysis of excretion samples,allowing the detection of carboxy-finasteride for up to 49 h in urine specimen collected after an oral administration of 5 mg of finasteride.
文摘Aim: To evaluate possible results with the stimulation use of minoxidil and the strengthening of hair roots with nutritional cyclical supplements, resulting in increased hair regrowth, without the use of anti androgens and enzyme blockers. Methods: This prospective controlled clinical trial compares the current acknowledged form of treatment for hair loss within two controlled groups for both men and women against the use of cyclical nutritional therapy and minoxidil 2%. One hundred patients in each of the 4 groups, a total of 400 patients, were followed for 1 year. The progress was evaluated every 2 months with computerised measurements of hair density, hair calibre, global photography and uniquely designed self-assessment scores. Results: The use of nutritional supplements showed consistent improvements in both treatment groups of men and women against the controlled groups with a correction of hair fall and minimum 18% increased density within 2 months with further improvement to a maximum of 156% over 1 year. Conclusion: Hair loss occurs when weak, sensitive, follicles are affected by multiple causes. Hair regrowth can be achieved consistently and safely by strengthening the hair roots and promoting hair growth without necessarily depending on the use of anti androgens.
基金Supported by the National Research Council(CNPq)Foundation for Science and Technology of the State of Pernambuco(FACEPE)Personnel Improvement Coordination-CAPES/PROCAD/NF/no 1415/2007,Brazil
文摘Objective: To explore the effects of aqueous extract from Phthirusa pyrifolia leaves(67 mg/kg body weight for 12 days) on the reproductive function of male Wistar rats through oral administration.Methods: Animals(n = 30), aged 13 weeks and weighing(378.5 ± 5.0) g, were housed in a vivarium under controlled environmental conditions [photoperiod of 12 h light/dark,temperature of(23 ± 1)C] and were fed standard rations ad libitum. The experiment ran for 12 days, wherein animals were divided into three groups: negative control(n = 6)received water, positive control(n = 12) with finasteride at a concentration of 1.0 mg/kg;and a test group(n = 12) submitted to aqueous extract. At the end of the experiment, the animals were sacrificed and submitted to analyses.Results: The morphological results of the testes showed that the aqueous extract induced significant changes in the diameter and cross-sectional area of the seminiferous tubules as well as the thickness of the seminiferous epithelium. Furthermore, the extract was able to abruptly decrease testosterone concentrations by about 81.88% in the treated group when compared with the negative control,(47.0 ± 4.8) ng/d L and(255.0 ± 2.0) ng/d L,respectively, and 76.8%,(211.0 ± 8.7) ng/d L, when compared with finasteride. However,the extract causes neither liver damage nor impairment of renal function.Conclusions: These results suggest that the high amounts of flavonoids shown to be in the extract may be responsible for its hepato-protective effects and suggest a possible decrease in the libido and reproduction of rats.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science,ICT & Future Planning(NRF-2016R1C1B2011827)
文摘Objective：To evaluate the efficacy of Bawu Decoction（八物汤,BWD,Palmul-tang in Korean）against benign prostatic hyperplasia（BPH）.Methods：Twenty-four male Wistar rats were divided into 4 groups,with 6 rats in each group.The 4 study groups included sham-operated group（CON）,BPH model group,finasteride-treated group,and BWD-treated group.All the groups except CON group received a subcutaneous injection of 10 mg/kg of testosterone,while CON group received saline.Finasteride at a dose of 5 mg/kg was administered to the finasteride-treated group for a period of 4 weeks.BWD group received BWD at a dose of 200 mg/kg for 4 weeks.The prostatic weight,prostate weight to body weight ratio,relative prostate weight ratio,serum testosterone and dihydrotestosterone（DHT）level,and histological analysis of prostatic tissue were analyzed.Results：Compared to BPH model group,BWD administration was associated with reductions in prostatic weight,prostate and relative prostate weight ratio weight to body weight ratio（P〈0.05）.The concentration of serum testosterone and DHT were higher in BPH group compared with CON group（P〈0.05）.Administration of finasteride and BWD suppressed the elevation of serum testosterone and DHT levels significantly（both P〈0.05）.In addition,BWD suppressed the growth of prostatic tissue（P〈0.05）.Conclusion：BWD has suppressant effects on development of BPH through inhibition of serum testosterone and DHT.
文摘Aim:The reason why non-calibrated hair variables poorly estimate scalp hair coverage during hair growth studies was studied.Methods:Hair productivity integrates density,diameter and daily hair growth rate.Cross-sectional studies have established hair productivity in female and male patients(480 vs.90 controls)with self-evaluation of hair loss,phototrichogram(CE-PTG-EC)and scalp coverage scoring,(SCS).Tracking productivity of individual hair follicular units from longitudinal studies challenged the application of our methods during drug trials.Results:Hair loss means decreased productivity and increased“time to complete coverage”.The hair mass index(HMI)linearly connects productivity with clinical perception of coverage,i.e.,SCS.The ensuing HMI abacus translates independently of gender,age,pattern or severity and unravelled unequal intervals between categories of the Ludwig and Hamilton classifications.With one severity grade shift,time to complete coverage varied from 21-51 days,i.e.,no equality.During longitudinal studies,SCS detected improved productivity,reflecting clinically relevant responses,but remained stable in the absence of significant productivity variations.Follicular unit labelling and individual hair growth tracing showed that reversal of miniaturised hair follicles does not play a major role during drug-induced hair regrowth.The latter reflects re-activation of resting-dormant terminal hair follicles.The recovered productivity would not be possible once hair follicles enter the phase of structural-functional irreversible miniaturisation.Conclusion:Besides pattern identification,density of nanohair and HMI appear as innovative diagnostic approaches.Abrupt transformation(within one cycle)of terminal hair follicles into miniaturised ones and its reversal as the effect of active FDA-approved drugs remain highly improbable.
