This study aimed to compare the gonadotropin-releasing hormone agonist (ultra-short) protocol versus (short and long) protocols on ovarian reserve in women undergoing intracytoplasmic sperm injection

开始日期2022-10-15

申办/合作机构

Tanta University

NCT05050084 / Recruiting临床3期IIT

Parallel Phase III Randomized Trials of Genomic-Risk Stratified Unfavorable Intermediate Risk Prostate Cancer: De-Intensification and Intensification Clinical Trial Evaluation (GUIDANCE)

This phase III trial uses the Decipher risk score to guide intensification (for higher Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better match therapies to an individual patient's cancer aggressiveness. The Decipher risk score evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk scores, this trial compares radiation therapy alone to the usual treatment of radiation therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation therapy blocks the production or interferes with the action of male sex hormones such as testosterone, which plays a role in prostate cancer development. Giving radiation treatment alone may be the same as the usual approach in controlling the cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy. In patients with higher Decipher gene risk, this trial compares the addition of darolutamide to usual treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading.

开始日期2021-11-03

申办/合作机构

NRG Oncology

[+1]

NCT04513717 / Recruiting临床3期IIT

Parallel Phase III Randomized Trials for High Risk Prostate Cancer Evaluating De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk With Radiation (PREDICT-RT*)

This phase III trial compares less intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in treating patients with high risk prostate cancer and low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in patients with high risk prostate cancer and high gene risk score. Apalutamide may help fight prostate cancer by blocking the use of androgen by the tumor cells. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving a shorter hormone therapy treatment may work the same at controlling prostate cancer compared to the usual 24 month hormone therapy treatment in patients with low gene risk score. Adding apalutamide to the usual treatment may increase the length of time without prostate cancer spreading as compared to the usual treatment in patients with high gene risk score.

开始日期2020-12-15

申办/合作机构

NRG Oncology

[+1]

100 项与醋酸布舍瑞林相关的临床结果

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100 项与醋酸布舍瑞林相关的转化医学

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100 项与醋酸布舍瑞林相关的专利（医药）

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1,431

项与醋酸布舍瑞林相关的文献（医药）

2024-11-18·ACS Applied Bio Materials

Mechanistic Model for Drug Release from PLGA-Based Biodegradable Implants for In Vitro Release Testing: Development and Validation

Article

作者: Mittapelly, Naresh ; Telaprolu, Krishna Chaitanya ; Bois, Frederic Y. ; Puttrevu, Santosh Kumar ; Djehizian, Alexandre ; Arjmandi-Tash, Omid ; McNally, Kevin ; Polak, Sebastian

Several factors can affect drug release from polylactide coglycolide (PLGA)-based formulations, including polymer and drug properties, formulation components, manufacturing processes, and environmental in vitro or in vivo conditions. To achieve optimal release profiles for specific drug delivery applications, it is crucial to understand the mechanistic processes that determine drug release from PLGA-based formulations. In the current study, we developed a mechanistic model for the in vitro drug release of PLGA-based solid implants. The model accounts for all known critical quality attributes (CQAs) and considers the most important release rate processes, including water or dissolution medium influx into the porous structure of the implant, initial noncatalytic hydrolysis of PLGA, autocatalytic hydrolysis, dissolution of oligomers and monomers into the aqueous medium, the liberation of the trapped solid drug from the polymer matrix, dissolution of the solid drug into the wetted pore network, diffusion of the dissolved drug out of the implant, and distribution of the dissolved drug into the dissolution medium. The model has been validated using in vitro release data obtained from implants of four drugs (buserelin, afamelanotide, brimonidine, and nafarelin). The model presented in this manuscript provides valuable insights into the kinetics and mechanism of drug release from PLGA-based solid implants and has demonstrated the potential for optimizing formulation design. The in vitro release model, coupled with physiologically based pharmacokinetic (PBPK) modeling, can predict the in vivo performance of implants and can be used to support bioequivalence studies in a drug development program.

2024-11-01·ANIMAL REPRODUCTION SCIENCE

Effect of repeated low doses of gonadotropin-releasing hormone on the secretion of luteinizing hormone and follicle-stimulating hormone, and ovarian function in dairy cows suffering from anovulation type I

Article

作者: Zduńczyk, Sławomir ; Crowe, Mark A ; Tobolski, Dawid ; Crowe, Mark A. ; Barański, Wojciech ; Nowicki, Arkadiusz

The aim of the study was to evaluate the effect of repeated low doses of gonadotropin-releasing hormone (GnRH) agonist buserelin once a day for 5 days on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release, and ovarian function in dairy cows with anovulation type I. The study was conducted on 10 anovulatory Polish Holstein-Friesian cows. Cows in Group 1 (n = 5) received 4 µg of buserelin intramuscularly. once a day for 5 days. Control cows from Group 2 (n = 5) received saline. Concentrations of progesterone, FSH, and LH in the blood were analysed using radioimmunoassay (RIA). Ovarian structures were monitored weekly after the end of treatment by ultrasound for 4 weeks. Injections of buserelin increased FSH and LH concentrations. Release of FSH and LH was largely variable, but there was significant (P < 0.001) interaction between time and treatment during all treatment days. The number of follicles in the treatment group was significantly greater (P = 0.029) than in the control group on day 5, the diameter of follicles on day 12 was also larger (P < 0.01) in treated than in control cows. Ovulation occurred in 4 of the 5 treated cows, but only in 1 of the control cows in the 40 days after treatment. In conclusion, repeated low doses of GnRH analogue buserelin once a day for 5 days may increase the concentration of FSH and LH in dairy cows with anovulation type I.

2024-10-01·DOMESTIC ANIMAL ENDOCRINOLOGY

Is it possible to replace eCG by GnRH in the hormonal protocol for timed artificial insemination in ewes during the breeding season?

Article

作者: Moraes, Fabiane P ; Maggi, Gabriel ; Ferreira, Rogério ; Oliveira, Fernando C ; Gonçalves, Paulo B D ; Vieira, Arnaldo D ; Mondadori, Rafael G ; Rovani, Monique T ; Gasperin, Bernardo G ; Pires, Otávio S ; Junior, Sérgio F Vargas

Hormonal protocols based on progestogens and equine chorionic gonadotrophin (eCG) are efficient for estrus and ovulation synchronization in ewes. Although eCG is indispensable during seasonal anestrus, it may not be necessary during the breeding season. Thus, we tested the hypothesis that GnRH is effective in replacing eCG during the breeding season allowing satisfactory ovulation rate, luteal function and conception rates after timed artificial insemination (TAI). Ewes (n = 134) with a minimum body condition score of 2.5 (0-5 scale) were treated with intravaginal devices (IVD) containing 60 mg of medroxyprogesterone acetate (MPA) for seven days and received 0.26 mg of sodium cloprostenol at the time of IVD removal. In Exp. 1, at IVD removal, ewes (n = 29) were allocated to three groups: eCG (200 IU at IVD removal; n = 10); eCG+GnRH (200 IU eCG at IVD removal and 4 µg of buserelin 36 h later; n = 10); or GnRH (buserelin 36 h after IVD removal; n = 9). Blood samples were collected 2, 6 and 12 days after TAI moment (54 h after IVD removal), for progesterone (P4) analysis. In Exp 2, the ewes were allocated to eCG (n = 10) or GnRH (n = 10) groups, as above described, and ovulation moment was evaluated 54, 66 and 78 h after IVD removal. In Exp 3, TAI was performed in ewes from eCG (n = 45) and GnRH (n = 40) groups using 100 × 10⁶ motile spermatozoa from a pool of semen collected from four rams. In Exp. 1, based on P4 levels, we confirmed that all the ewes ovulated (29/29) and there was no significant effect of group (P = 0.89) or group x day (P = 0.18) on P4 concentration, being observed a significant effect of day (P = 0.0001). In Exp. 2, the maximum DF diameter (P = 0.26) and ovulation moment (P = 0.69) did not differ between groups. In Exp. 3, pregnancy rate was significantly lower (P = 0.02) in GnRH (22.5 %; 9/40) compared to eCG (46.7 %; 21/45). The results indicate that, although ovulation and luteal function were not altered after eCG, eCG+GnRH or GnRH treatment, GnRH alone before TAI cannot be used to replace eCG treatment during the breeding season.

项与醋酸布舍瑞林相关的新闻（医药）

2024-07-30

·GlobeNewswire-Health Care

H1 2024 Results - Focus-27 strategic plan on track with timely execution of the operational roadmap

Press ReleaseParis, 30th July 2024 Net Sales down 9.6% year-on-year – Core EBITDA margin at 10.6%Accelerated commercial momentum with clients other than Sanofi, with Net Sales up 2.9%, excluding the Brindisi site, where production was temporarily suspendedEnhanced effectiveness across the entire organization, with sizeable improvements in industrial efficiencies€10 million Free Cash Flow before financing, driven by strengthened financial disciplineFY 2024 guidance confirmed " Our H1 actions set the foundations of our more agile, streamlined, and value-creating model. Over the past months, with the entire organization's support, we have made significant progress in deploying the four strategic pillars of our operational roadmap. Thanks to a comprehensive mitigation plan, we will resume shipment and production in Brindisi in the coming weeks." said Ludwig de Mot, Chief Executive Officer of EUROAPI. "Confident in the collective success of our plan, we are in advanced discussions with our stakeholders to finalize the financing of FOCUS-27 in the coming weeks, which will pave the way for long-term profitable growth.” €448.7 million in Net Sales, down by 9.6%1, shaped by the strong decrease in volumes from Sanofi and the suspension of production in Brindisi, which overshadowed the positive momentum of sales to clients other than Sanofi Brindisi GMP license reactivated mid-July; shipments and production to restart gradually during Q3 2024 Signature of a major CMO commercial phase contract with a global animal health company and a development and manufacturing agreement with Priothera, a biotechnology company specializing in oncology €47.6 million Core EBITDA, with a 10.6% Core EBITDA margin, down from 12.6% in H1 2023. Price increases and product mix, industrial efficiencies, and the impact of the revised commercial contractual clauses with Sanofi over the period partially offset the unfavorable fixed-cost absorption. €(1.4) million EBITDA, including €47.2 million exceptional costs related to the implementation of FOCUS-27. €(170.2) million Net Debt compared to €(171.0) million at the end of December 2023, with €10.0 million Free Cash Flow before financing, compared to €(111.2) million for the same period last year, driven notably by Controlled CAPEX (€61.3 million, of which 56% dedicated to growth) Improved Operating Working Capital thanks to a rigorous inventory reduction program and better cash collection €(34.8) million Net income, compared to €62.8 million in H1 2023 H1-2024 Key figures (in € millions)H1-2024H1-2023Net Sales448.7496.6Year-on-year change in %-9.6%+2.6%Gross profit98.097.0Gross Profit Margin21.8%19.5%EBITDA(1.4)52.1Core EBITDA47.662.5Core EBITDA Margin10.6%12.6%Net Income(34.8)62.8Basic EPS (in euros)(0.37)0.67 2024 outlook confirmed Between 8% and 11% decrease in 2024 Net Sales compared to 2023 on a comparable basis, with a second-half performance slightly exceeding that of the first half due to a phasing impact in CDMO. Core EBITDA margin objective expected between 4% and 7%. The positive impact in H1 of the revised contractual clauses with Sanofi will be lower in the second half. FOCUS-27 plan in action The execution of FOCUS-27 is on track, with several initiatives launched during the first half, and the discussions with the Revolving Credit Facility banking syndicate to finalize the financing announced on June 26, 2024, are in the advanced stage. Streamlined value-added portfolio List of the discontinued 13 APIs communicated to our clients; phase-out roadmap almost completedAccelerated momentum in Opiates, prompted by improving competitive positions Focused CDMO offer Solid and qualitative new late-stage projects with 3 marketed small molecules for large and mid-size pharma and food companies (including GMP intermediates). Increasing momentum in large molecules, with 5 early-stage projects in H1, mainly from large pharma companies, including 4 promising new oligonucleotides and 1 peptide-PMO conjugate project. Rationalized industrial footprint Ramp down of workshops initiated in Frankfurt (9 APIs to be discontinued), and Vertolaye (2 APIs to be discontinued)Inventory reduction program on track Haverhill divestment process well advanced; completion expected in 2025 Organizational transformation Headcount reduction plan initiated in Haverhill following the decrease in volumes of SevelamerContinued enhancement of the management teams across the group, including the reorganization of the Executive leadership team. H1-2024 Net Sales EUROAPI H1-2024 Net Sales reached €448.7 million, -9.6% versus H1 2023 and -9.3% at Constant Exchange Rates. Net sales per type of activity (in € millions)H1H1-2023ChangeAPI Solutions – Other clients168.6169.8-0.7%API Solutions – Sanofi163.7192.7-15.0%API Solutions332.4362.4-8.3%CDMO – Other clients72.382.7-12.7%CDMO – Sanofi44.151.4-14.2%CDMO116.4134.2-13.3%Net sales448.7496.6-9.6%Total Net Sales – Sanofi207.8244.1-14.9%Total Net Sales – Other clients 240.9252.5-4.6% API Solutions API Solutions' net sales decreased by 8.3% to €332.4 million. Sales to Sanofi decreased by 15.0% due to strong volume decrease, notably in Sevelamer, produced in Haverhill, and the suspension of production in Brindisi. H1 net sales include €29 million related to the revision of the historical MSA contractual clauses agreed with Sanofi in February 20242, primarily Buserelin’s3 stock clearance. Sales to Other Clients decreased by 0.7%, impacted by the temporary suspension of API production in Brindisi. Excluding Brindisi’s site, net sales would have grown 3.4%, driven by the cross-selling strategy (representing 9.1% of H1 API Solutions sales to Other Clients) and an increased customer base (22 new clients added in H1). CDMO CDMO sales decreased by 13.3% to €116.4 million. Sales to Sanofi decreased by 14.2% on the back of a strong H1 2023 performance, which was boosted by stock replenishment of Pristinamycin, an anti-infective produced exclusively for Sanofi in Elbeuf. H1 2024 sales benefited from the ramp-up of a commercial phase contract in Large Molecules.Sales to Other Clients decreased by 12.7% due to the temporary suspension of production in Brindisi, which affected a commercial phase contract. H1 2024 performance was also penalized by the downsizing of two large historical commercial phase contracts (approximately -10 M€), which more than offset the increase in revenue from new contracts. Excluding the impact of Brindisi, total CDMO sales to clients other than Sanofi would have grown by 1.8%, with increased revenues from early-stage projects. Throughout the semester, 14 new CDMO contracts were signed, and eight projects were completed, including two in late stage with Sanofi, and two projects were put on hold. (Number of CDMO projects)Phase 1 and earlierPhase 2Phase 3Commercial PhaseTotalLarge molecules742417Highly potent molecules1 12Biochemistry molecules derived from fermentation2 68Complex chemical synthesis molecules9772346Total191193473 Net Sales per type of molecule (in € million)H1-2024H1-2023ChangeLarge molecules58.835.0+67.9%Highly potent molecules47.143.7+7.8%Biochemistry molecules derived from fermentation43.785.5-48.8%Complex chemical synthesis molecules299.1332.4-10.0%Net Sales448.7496.6-9.6% Large molecules increased by 67.9% to €58.8 million, driven by the stock clearance of Buserelin, and the ramp-up of a commercial phase contract in Large Molecules with Sanofi. Highly potent molecules were up 7.8% to €47.1 million on the back of a low comparison base in H1 2023, which was impacted by the suspension of Prostaglandins’ production.Biochemistry molecules derived from fermentation decreased 48.8% to €43.7 million. While H1 2023 performance was boosted by stock replenishment of Pristinamycin, H1 2024 was impacted by the temporary suspension of API production in Brindisi. Complex chemical synthesis molecules decreased by 10.0% to €299.1 million, mainly impacted by the decreasing volume demand from Sanofi. Financial performance (in € million)H1-2024H1-2023Net Sales448.7496.6Other revenues2.21.9Gross profit98.097.0Gross Profit Margin21.8%19.5%EBITDA(1.4)52.1Non-recurring costs49.010.4Core EBITDA47.662.5Core EBITDA Margin10.6%12.6%Operating Income(33.4)16.0Finance revenues/costs(8.1)(3.3)Income before tax(41.5)12.6Income tax expense6.750.1Net income/(loss)(34.8)62.8EPS (in euros)(0.37)0.67Average number of shares outstanding (in millions)94.393.9Fully diluted EPS (in euros)(0.37)0.66Average number of shares after dilution (in millions)95.995.5 Gross profit was €98.0 million, compared to €97.0 million in H1 2023, with the gross profit margin up 231 basis points year-on-year to 21.8%. The exceptional impact of Buserelin’s stock clearance, positive price and mix effect, lower energy and raw materials prices, and improved industrial performance more than offset unfavorable fixed-cost absorption as we sold in H1 24 products manufactured at the peak level of the past 18 months inflation cycle. Core EBITDA amounted to €47.6 million, down 23.8% compared to €62.5 million in H1 2023. The core EBITDA margin was 10.6%, compared to 12.6% in H1 2023. The increase in OPEX was mostly driven by the company's transformation and reorganization. EBITDA was €(1.4) million compared to €52.1 million in H1 2023. The 49.0 million non-recurring costs include €47.2 million in exceptional items4, of which €33.8 million of idle costs5 linked to the execution of FOCUS-27, including the ramp-down of two workshops in Frankfurt started in H1 2024 and reduced inventories in Vertolaye €9.0 million of internal and external costs related to the transformation of the company €4.4 million of employee-related expenses, including redundancy plans. Key components of the change in Core EBITDA marginH124/H123 in percentage points (rounded figures)H1 2023 Core EBITDA margin12.6%Volume-0.0 ptsPrice and Mix+3.0 ptsImpact of Buserelin’s stock clearance+2.1 ptsIndustrial performance+2.4 ptsEnergy and Raw Materials+1.2 ptsUnfavorable fixed cost absorption-5.5 ptsOther Gross Margin impacts -1.9 ptsOPEX -2.9 ptsBrindisi site, including the impact of the suspension of production-0.3 ptsH1 2024 Core EBITDA margin10.6% Operating Income was €(33.4) million compared to €16.0 million in H1 2023. Financial income was €(8.1) million, compared with €(3.3) million in H1 2023, due notably to the increase in interest rates and the full drawdown of the RCF. Income before tax was €(41.5) million6. Net income was €(34.8) million in H1 2024. Net Debt Position and Cash Flow (in € million)30 June 2024Net cash/(Debt) position – December 2023(171.0)Cash Flow from Operating activities71.2Of which change in Working Capital66.1 (Increase)/decrease in inventories 4.1 (Increase)/decrease in trade receivables 40.0 Increase/(decrease) in trade payables (16.2) Other current assets and liabilities 38.3Cash Flow from Investing Activities(61.3)of which CAPEX(61.3)Cash Flow from Financing activities(8.3)Exchange rate((0.9)Net Cash/(Debt) position – June 2024(170.2) The decrease in Net Debt position, €(170.2) million compared to a €(171.0) million at the end of December 2023, was notably driven by Working Capital, including the improvement in inventories. Improved cash collection drove the change in Trade receivables, with DSO down to 53 compared to 56 in December 2023 and 70 in H1 2023. Other current assets and liabilities include a €27 million variation in VAT tax reimbursement. Capex reached €(61.3) million (13.7% of Net Sales), of which 56% were dedicated to growth projects, including increased capacities for Peptides and Oligonucleotides, Vitamin B12, and Prostaglandins. Free Cash Flow before financing activities was €10.0 million, compared to €(111.2) million at the end of June 2023.7 (in € million)30 June 202431 December 2023Bank Cash Balances282.834.5Revolving Credit Facilities(453.0)8(205.5)Net Debt Position(170.2)(171.0) Net Debt to Core EBITDA restated for IFRS 16 was 2.38x, below the RCF covenant of 4.0x.ESG Roadmap EUROAPI ESG roadmap is on track to achieve its 2030 goals and has recently achieved: 100% of its sites certified ISO14001 (environment management) and ISO50001 (energy management). CDP score B, which indicates that the group is addressing the environmental impacts of its business and ensures good environmental management. Main H1 2024 events On January 25, 2024, EUROAPI announced that it had initiated a pivotal collaboration with SpiroChem, a leading Contract Research Organization (CRO).On March 14, 2024, EUROAPI announced the pause of API production at the Brindisi site in Italy after identifying quality control deficiencies and decided to suspend its full-year 2024 guidance.On May 23, 2024, EUROAPI announced a Contract Manufacturing Organization (CMO) agreement with a global animal health company to supply key veterinary product. The total contract value is expected to range between €130 and 150 million over 2025-2029.On June 6, 2024, EUROAPI received official notification from the European Commission that it had been selected as one of the 13 companies eligible to share up to EUR 1 billion in total public funding under the Important Project of Common European Interest (IPCEI) dedicated to the pharmaceutical sector.On June 18, 2024, EUROAPI announced the implementation of a 5-year development and manufacturing agreement with Priothera, a biotechnology company specializing in treating hematological malignancies and improving CAR-T cell therapies.On June 26, 2024, EUROAPI detailed the FOCUS-27 strategy and announced its target to generate €75 million to €80 million annual run-rate incremental Core EBITDA by the end of 2027. More detail on EUROAPI’s website: EUROAPI is moving ahead with its FOCUS-27 plan, setting the foundations for future profitable growth | EUROAPIannounced that the Brindisi site will progressively resume shipments and production during Q3 2024. Glossary and definition of non-GAAP indicators EBITDA and Core EBITDA EBITDA corresponds to operating income (loss) restated for depreciation and amortization and net impairment of intangible assets and property, plant and equipment.Core EBITDA thus corresponds to EBITDA restated for restructuring costs and similar items (excluding depreciation and write-downs), allocations net of reversals of unutilized provisions for environmental risks, and other items not representative of the Group’s current operating performance or related to the effects of acquisitions or disposals. Cash Flow before Financing activities Cash Flow before Financing activities corresponds to the sum of Cash Flow from Operating Activities and Cash Flow from Investing Activities as presented in the consolidated statement of Cash Flow. Months on Hand (MOH) Net Inventory value at the of the period divided by Net Sales New clients Clients representing at least €50 thousands of net sales on the year. Cross Selling Selling a different product to an existing client that is already buying one or several products from EUROAPI. Early-stage and Late-stage projects Early-stage: pre-clinical, phase 1, and phase 2Late-stage: phase3, in validation, and commercial Presentation of H1-2024 results An analysts’ conference call will be held by EUROAPI’s management tomorrow (31 July 2024) at 8:30 a.m. CET via an audio webcast (live and replay), and the results presentation will be available on the corporate website 2024 Half year results | EUROAPI Financial agenda (all dates to be confirmed) 11 February 2025: FY 2024 Results21 May 2025: 2025 AGM29 July 2025: H1 2025 results About EUROAPIEUROAPI is focused on reinventing active ingredient solutions to sustainably meet customers’ and patients’ needs around the world. We are a leading player in active pharmaceutical ingredients with approximately 200 products in our portfolio, offering a large span of technologies while developing innovative molecules through our Contract Development and Manufacturing Organization (CDMO) activities. Taking action for health by enabling access to essential therapies inspires our 3,650 people every day. With strong research and development capabilities and six manufacturing sites, all located in Europe, EUROAPI ensures API manufacturing of the highest quality to supply customers in more than 80 countries. EUROAPI is listed on Euronext Paris; ISIN: FR0014008VX5; ticker: EAPI). Find out more at www.euroapi.com and follow us on LinkedIn. Media Relations contact:Laurence BollackTel.: +33 (0)6 81 86 80 19mr@euroapi.com Investor Relations contacts:Sophie Palliez-CapianTel.: +33 (0)6 87 89 33 51Sophie.palliez@euroapi.com Camille RicotierTel: +33 (0)6 43 29 93 79Camille.ricotier@euroapi.com Forward-Looking StatementsCertain information contained in this press release is forward looking and not historical data. These forward-looking statements are based on opinions, projections and current assumptions including, but not limited to, assumptions concerning the Group’s current and future strategy, financial and non-financial future results and the environment in which the Group operates, as well as events, operations, future services or product development and potential. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Forward looking statements and information do not constitute guarantees of future performances, and are subject to known or unknown risks, uncertainties and other factors, a large number of which are difficult to predict and generally outside the control of the Group, which could cause actual results, performances or achievements, or the results of the sector or other events, to differ materially from those described or suggested by these forward-looking statements. These risks and uncertainties include those that are indicated and detailed in Chapter 3 “Risk factors” of the Universal Registration Document filed with the French Financial Markets Authority (Autorité des marchés financiers, AMF) on April 5, 2024. These forward-looking statements are given only as of the date of this press release and the Group expressly declines any obligation or commitment to publish updates or corrections of the forward-looking statements included in this press release in order to reflect any change affecting the forecasts or events, conditions or circumstances on which these forward-looking statements are based. Appendix Consolidated Income Statement (in € millions)30-Jun-2430-Jun-23Net sales448.7 496.6 Other revenues2.2 1.9 Cost of sales(352.9)(401.4)Gross profit98.0 97.0 Selling and distribution expenses(18.7)(21.3)Research and development expenses(13.9)(13.3)Administrative and general expenses(46.6)(42.8)Other operating income1.3 0.7 Impairment of assets(3.9) Restructuring costs and similar items(49.7)(4.3)Operating income(33.4) 16.0 Financial expenses(11.2)(5.3)Financial income3.1 1.9 Income/(loss) before tax(41.5) 12.6 Income tax expense6.7 50.1 Net income/(loss)(34.8) 62.8 Number of shares outstandings94.393.9EPS(0.37)0.67Diluted number of shares 95.995.5EPS diluted(0.37)0.66 Consolidated Balance Sheet (in € millions)30-Jun-2431-Dec-23Goodwill4.6 4.6 Property, plant and equipment469.0 468.9Right-of-use assets35.2 37.2Intangible assets38.9 34.2Other non-current assets6.7 9.0Deferred tax assets85.7 79.2Non-current assets640.2633.1Inventories638.7 644.8Trade receivables176.7 216.3Other current assets57.5 83.7Cash and cash equivalents282.8 34.5Current assets1,155.8979.3Total assets1,795.91,612.4(in € millions)30-Jun-2431-Dec-23Equity attributable to owners of the parent889.5927.7Total equity889.5927.7Non-current lease liabilities14.515.5Provisions155.3158.6Other non-current liabilities0.00.0Deferred tax liabilities0.81.6Non-current liabilities170.6175.7Trade payables143.6159.6Other current liabilities135.1139.3Current lease liabilities4.34.6Short-term debt and other financial liabilities452.8205.4Current liabilities735.9508.9Total equity and liabilities1,795.91,612.4 Consolidated Statements of Cash Flow (in € millions)30-Jun-2430-Jun-23Net income / (loss)(34.8)(62.8)Depreciation & amortization 32.0 36.1 Net change in current & deferred taxes(6.7)(50.1)Other profit or loss items with no cash effect and reclass of interest 14.7 8.2 Operating cash flow before changes in working capital 5.1 56.9 (Increase)/decrease in inventories 4.1 (66.0)(Increase)/decrease in trade receivables 40.0 30.1 Increase/(decrease) in trade payables(16.2)(49.0)Net change in other current assets and other current liabilities 38.3 (10.3)Net cash provided by operating activities 71.2 (38.2) Acquisitions of property, plant and equipment and intangible assets(61.3)(73.1)Acquisition of shares on consolidated entities, net of cash acquired - Sales/Acquisitions to/from Group entities 0.0 - Net cash (used in) investing activities(61.3)(73.1)Capital increases - - Repayment of lease liabilities(2.7)(4.6)Net change in short-term debt 246.0 100.0 Finance costs paid(4.1)(2.0)Acquisitions and disposals of treasury shares(0.0)(0.2)Other net cash flow arising from financing activities(0.3)(0.0) Net cash provided by financing activities 238.8 93.2 Impact of exchange rates on cash and cash equivalents(0.5) 0.6 Net change in cash and cash equivalents 248.3 (17.5) Cash and cash equivalents at beginning of period 34.5 74.5 Cash and cash equivalents at end of period 282.8 57.0 Reconciliation of Consolidated Operating Income (EBIT) to restated Core EBITDA (in € millions)30-Jun-2430-Jun-23Operating income(33.4) 16.0 Depreciation and amortization 32.0 36.1 EBITDA(1.4) 52.1 Restructuring costs and similar items (excluding depreciation and amortization) 47.2 4.3 Of which idle costs33.8 Of which employee-related expenses4.4 Of which internal and external costs related to FOCUS-27, and transformation9.04.3Allocations net of reversals of unutilized provisions for environmental risks(0.2)(0.3)Other 2.0 6.3 Core EBITDA 47.6 62.5 Core EBITDA10.6%12.6% Idle costs are mainly affecting Vertolaye, with the inventory reduction program being the main business factor, as well as the discontinuation of 2 APIs, Frankfurt, with the decision to discontinue 9 APIs (the ramp down of two workshops has already started in 2024). Employee-related expenses of €4.4 million include the impact of the redundancy plan announced in EUROAPI UK and severance payments in connection with the renewal of the Executive leadership teams. Restructuring costs correspond to expenses incurred in connection with the transformation or reorganization of the EUROAPI Group’s operations and support functions. These costs include collective redundancy plans, compensation awarded to third parties for the early termination of contracts, commitments made in connection with transformation and reorganization decisions, and idle costs related to the temporary shutdown of sites or production lines associated with such programs.They also include accelerated depreciation charges arising from closures of production facilities (including leased facilities), and losses on any resulting asset disposals.In addition, restructuring costs and similar items comprise expenses (both internal and external)incurred in connection with FOCUS-27. 1 All comments in this press release are made compared to H1 2023 figures unless stated otherwise2 Full-year expected impact: €38 million (Regulated Agreement approved by the May 22nd AGM)3 Buserelin is a large molecule used primarily in the treatment of prostate cancer and endometriosis.4 See appendix page 13 5 Under-activity triggered by the implementation of FOCUS-27 6 H1 2023 income tax included €46.8m deferred tax income related to the revaluation of EUROAPI’s Hungarian assets.7 See detailed in Consolidated Cash Flow Statement page 128 RCF: €451 million + €2 million accrued interests Attachment EUROAPI - Press release - July 30, 2024

财报临床1期

2024-03-03

·药渡

鼻内递送（Intranasal）的多肽药物发展

人体中已鉴定出超过7000种内源性肽，[1] 并且发现这些肽在控制多种生理功能中起着至关重要的作用。美国、欧洲和日本监管部门已经批准了超过150种多肽药物和诊断试剂，用于诊断和治疗多种疾病，包括癌症、感染和神经退行性疾病。此外，多肽已被开发为激素替代品和疫苗。毫无疑问，多肽药物的药代动力学特性是阻碍多肽药物更广泛应用的一个重要因素。由于极低的口服生物利用度和高度的酶降解，绝大多数的多肽药物通过静脉、肌肉和皮下注射等方式实现药物递送。寻找替代注射的递送方式成为了多肽制剂一个关键的研发领域。多肽的鼻内 (IN，intranasal) 递送作为一种潜在的无创递送途径受到了相当大的关注，多肽药物可以通过该途径轻松进入系统循环。鼻腔给药提供了几个优势，包括鼻腔相对较大的可吸收表面积、鼻组织的高渗透性和血管特性，以及避免胃降解和肝脏首过代谢。[2]目前已经上市的多肽喷鼻剂包括以下产品：1 Calcitonin Salmon (商品名Miacalcin®) Miacalcin®中的有效成分是多肽calcitonin salmon（鲑鱼降钙素），它是鲑鱼中发现的一种降钙素激素。与人类降钙素一样，鲑鱼降钙素是一种肽激素，由甲状腺的滤泡旁细胞分泌，以应对高钙血症，并通过促进肾脏排泄来降低血钙和血磷。Miacalcin®鼻喷雾剂用于治疗绝经至少5年的女性的骨质疏松症。它应该与足够的钙和维生素D摄入一起发挥作用。Miacalcin®鼻腔喷雾剂面向那些不适合替代疗法的患者，例如其他疗法不适合的患者或不耐受或不愿使用其他疗法的患者。2Desmopresin (商品名Stimate®) Stimate®鼻腔喷雾剂适用于凝血因子 VIII活性水平大于5%（轻型）的血友病患者。Stimate®鼻喷雾剂含有作为活性物质的醋酸去氨加压素（desmopressin acetate），它是天然激素精氨酸加压素 (Arginine vasopressin) 的合成类似物。一喷（ 0.1 mL, 150 μg）Stimate®鼻腔喷雾溶液具有约600国际单位的抗利尿活性。Stimate®Nasal Spray的半衰期在3.3到3.5小时之间，鼻内剂量范围为150到450 μg 。Stimate®鼻腔喷雾剂的血浆浓度在给药后约40至45分钟达到最大值。当以1.5 mg/mL的溶液形式通过鼻内途径给药时，Stimate®鼻喷剂的生物利用度在3.3%到4.1%之间。3Desmopressin (商品名Octostim®) 同样是desmopressin, 它最初的开发商Ferring制药公司将其开发成了不同的喷鼻剂。Octostim®是一款抗利尿药，它可用于治疗中枢性尿崩症，这是一种由于缺乏抗利尿激素 (ADH) 而导致肾脏无法保存水分的疾病。这种情况会导致尿频和口渴。它还用于治疗头部受伤或某些类型的脑部手术后可能出现的暂时性口渴和排尿增加。对于这些用途，去氨加压素鼻腔溶液通过帮助减少肾脏产生的尿量来起作用。4Desmopressin (商品名Minirin®) Minirin® (desmopressin) 主要适应症：原发性夜间遗尿症Minirin®鼻喷雾剂适用于原发性夜间遗尿症的管理。它可以单独使用或以辅助行为调节其他非药物干预。它已被证明在某些常规疗法难以治愈的病例中有效。中枢性颅内尿崩症Minirin®鼻腔喷雾剂适用于治疗中枢性颅内尿崩症，以及头部外伤或垂体区手术后暂时性多尿的抗利尿替代疗法。对治疗肾源性尿崩症无效。Minirin®鼻腔喷雾压缩泵每次喷雾可输送0.1 mL（10 μg）醋酸去氨加压素。除了喷鼻剂外，Minirin®也有口服片剂的形式。5Desmopressin（商品名DDAVP） DDAVP含有作为活性物质的醋酸去氨加压素具有抗利尿作用，1 mL（0.1 mg）鼻内DDAVP约为400 IU的活性。鼻内DDAVP的双相半衰期在快相和慢相中分别为7.8分钟和75.5分钟，而另一种形式的赖氨酸加压素（lysine vasopressin）则为 2.5分钟和14.5分钟。因此，鼻内DDAVP在每次给药后可迅速产生抗利尿作用并持续较长的药效时间。6Buserelin（商品名Suprefact®） Buserelin用于男性治疗晚期前列腺癌，但不是治愈方法。大多数类型的前列腺癌需要雄性激素睾丸激素才能生长和扩散。Buserelin通过减少身体产生的睾酮量起作用。这种作用有助于减缓或阻止癌细胞的生长，并有助于缓解排尿疼痛/困难等症状。布舍瑞林也用于女性子宫内膜异位症的治疗。它通过减少身体产生的女性荷尔蒙雌激素来起作用。这种作用有助于缩小异常组织，并减轻子宫内膜异位症的症状（例如，骨盆疼痛、痛经）。Buserelin是一种人造激素，类似于人体产生的天然激素“促性腺激素释放激素” （GnRH）。尽管buserelin的使用可以促进黄体生成素（luteinizing hormon, LH）和促卵细胞素（follicle-stimulating hormone, FSH）的分泌（激动剂），然而随着buserelin的长期给药，GnRH受体将变得脱敏并完全停止对buserelin和内源性GnRH的反应。GnRH受体的深度脱敏导致垂体前叶LH和FSH分泌减少，随后性腺性激素产生停止，男性精子发生显著减少或消失，女性无排卵，并实现“饿死”癌细胞的目的。Suprefact每mL鼻内水溶液含有1.06 mg醋酸buserelin（相当于 1 mg buserelin游离碱）。对于前列腺癌，通常的起始剂量是buserelin 500 µg，通过皮下注射，每8小时一次，持续7天。随后进行维持治疗，每天一次注射200 µg buserelin或每天3次递送400 µg鼻腔喷雾剂（每个鼻孔喷2 次）。使用buserelin治疗子宫内膜异位症的女性通常使用buserelin鼻腔溶液，剂量为400µg（每个鼻孔喷 2 次），每日3次。治疗通常持续6个月，但不应持续超过9个月。7Nafarelin （商品名Synarel®）同buserelin一样，nafarelin也是一种GnRH（促性腺激素释放激素）类似物（激动剂）。用于治疗子宫内膜异位症和性早熟。它还用于治疗子宫肌瘤，控制体外受精 (IVF) 中的卵巢刺激，并作为跨性别激素治疗的一部分。Synarel®这种药物适用于治疗男女儿童中枢性性早熟 (CPP, central precocious puberty)（促性腺激素依赖性性早熟）。每天用作鼻腔喷雾剂2至3次。Synarel®鼻用溶液中含有醋酸nafarelin（2 mg/mL）。在为Synarel®泵灌注后，该单元的每次启动都会输送约100 μL的喷雾，其中含有约200 μg nafarelin游离碱。一个喷雾瓶的内容物旨在提供至少60次喷雾。鼻内给药后，醋酸nafarelin被迅速吸收到体循环中。最大血清浓度在10到40分钟之间达到。在单次剂量200μg游离碱nafarelin后，观察到的平均峰浓度为0.6 ng/mL（范围为0.2至1.4ng/mL），而在单次剂量400 μg游离碱nafarelin后，观察到的平均峰浓度为1.8 ng/mL（范围0.5至5.3ng/mL）。400 μg剂量的生物利用度平均为2.8%（范围1.2至5.6%）。鼻内给药后nafarelin的平均血清半衰期约为3小时。大约80%的醋酸nafarelin在4°C时与血浆蛋白结合。[3]8Oxytocin（商品名Syntocinon）催产素鼻腔喷雾剂的用途范围从治疗焦虑症到自闭症。在临床试验中，催产素显示出治疗肥胖症的前景，并可能有其他超适应症用途。它是一种天然存在的激素，也可以作为补充剂使用。9Semax Semax 肽以其神经保护、益智和神经恢复特性而闻名。传统上，Semax曾用于治疗抑郁症和焦虑症。Semax最初是根据ACTH（Adrenocorticotropic Hormone，促肾上腺皮质激素）的分子结构开发的。正在进行的研究表明，Semax 可能对患有认知疾病（包括痴呆、中风、注意力缺陷多动症等）的个人非常有用，可能更好的增加注意力和记忆力，减少焦虑和抑郁症状，提高思维清晰度和注意力，减少压力的影响，因此在Semax被赋予了“脑力肽”的中文意译名称。Semax被应用于广泛的适应症，在医疗环境中，Semax已被规定用于治疗：焦虑症、缺血事件、中风、神经再生、多动症、阿片类药物戒断、帕金森病、阿尔茨海默病、血栓形成和胃病。值得注意的是，脑力肽主要在俄罗斯和乌克兰等国使用，在全世界大多数国家并未获得批准。1鼻内递送多肽药物的优势1 潜在的鼻子到大脑路线血脑屏障 (BBB) 是将治疗药物输送到中枢神经系统 (CNS) 的主要障碍，因为大多数大分子量物质在正常情况下都受到严格限制，无法穿过BBB。对于生物制剂，例如肽、蛋白质、单克隆抗体、寡核苷酸以及通过鼻-脑途径的基因和细胞疗法，鼻腔输送为它们提供了绕过 BBB而抵达脑部的潜在策略，从而为阿尔茨海默病、帕金森病和抗精神病药物引起的症状等适应症提供了新的治疗方法。2高疗效和快起效大多数生物制剂在胃肠道中容易被酶促降解，因此最常用的给药途径是注射。但当药物通过鼻内途径给药时，它们通过下鼻甲周围的呼吸区进入，呼吸区鼻粘膜血管丰富，内衬柱状上皮细胞具有较大的表面积（> 150 cm2），利于药物吸收，[4] 并且透过性很强。[5] 由于鼻内途径避免了胃肠道中的酶促降解和肝脏的首过代谢，因此它减少了限制药物吸收的常见屏障，有助于快速起效。3高度患者依从性相对于注射，鼻内递送的方式无疑将得到更高的患者依从性。良好的患者依从性对治疗效果很重要，对于鼻内药物产品尤其如此，必须定期和一致地给药以确保持续的治疗效果。患者对给药的满意度和舒适度高度决定了他们的依从性。鼻内途径既无创又具有很高的耐受性，扩大了患者自我给药的可能性和依从性。2鼻内递送面临的挑战1 粘液纤毛清除鼻部结构可以通过粘液纤毛清除快速清除试图进入呼吸道的物质，这是一个自然过程，鼻粘膜将粘液和沉积物从鼻子前部拖到喉咙，并在那里被吞咽。这意味着，留给鼻内给药的吸收窗口时间很短。自然的鼻循环也会影响吸收率。这是一个大约两个半小时的周期，其中鼻子的一侧比另一侧更拥塞，两侧交替进行。[6] 如果喷鼻剂剂量仅针对一次注射到鼻子中，那么吸收效果可能因使用哪个鼻孔而异。2吸收效果不佳生物制剂的鼻腔递送受到大分子量蛋白质或多肽药物的低膜渗透性限制。药物的这种低渗透性意味着需要使用吸收促进剂进行制剂，或者需要更大剂量的活性物质才能达到适当的治疗剂量。已经上市或目前处在临床阶段的IN多肽鼻内递送的生物利用度见表1。表1. IN递送多肽生物利用度[7]1．相对于皮下注射，Teriparatide单剂量20 µg IN喷雾剂对兔的相对生物利用度。 2．相对于皮下注射，Teriparatide单剂量160 µg IN喷雾剂对兔的相对生物利用度。 3．相对于皮下注射，Teriparatide单剂量200和400 µg IN喷雾剂对健康成人的相对生物利用度。4．相对于皮下注射，Teriparatide单剂量500和1000 µg IN喷雾剂对健康成人的相对生物利用度。5．Carbetocin不同制剂的相对生物利用度，单剂量60 µg/kg IN喷雾施用于兔。 3多肽鼻内递送制剂鼻内生物递送的制剂方式非常重要，可使用生物粘合剂或粘度调节剂来增加在多肽药物在鼻腔中的驻留时间，以减慢粘膜纤毛的快速清除并保留在鼻腔中的药物量，以允许发生充分吸收。吸收是制剂开发过程中需要深入研究的一个主要因素，可以使用多种策略对其进行优化，包括渗透增强剂、粘液溶解剂、粘膜粘附剂、原位胶凝剂和药物载体技术。粘膜粘附鼻腔凝胶是最突出的非侵入性剂型，药物可以通过它直接进入全身循环，避免首过效应并提高药物的潜在生物利用度。[8] 利用载药技术，或用修饰吸入颗粒表面以增强吸收的药剂技术，是一种强大的配方策略，当然其利用前提是保持药物结构完整性。例如，多肽脂化，当以干粉形式递送时，脂质体通过鼻粘膜的渗透性增加。[9] 其实这些技术在开发口服多肽制剂的技术平台上也发挥着类似的作用。在提高生物利用度这方面，口服递送与鼻内递送面临的挑战具有某些类似性，因此化学改性多肽药物对于两个领域都具有可利用性。— 总结 —鼻内给药是一种很有前途的生物给药途径，这反映在越来越多的上市治疗慢性疾病的产品上，以及目前正在进行的大量临床试验中，特别是那些专注于开发治疗由鼻腔引起的呼吸道疾病的药物的临床试验，例如Covid-19疫苗。很多多肽神经递质（神经肽），也可以通过鼻内给药的方式绕过血脑屏障而抵达中枢神经系统。相信鼻内给药会在这些领域发挥越来越关键的作用。参考文献：（上下滑动查看更多）[1] Fosgerau, K. et al. Peptide therapeutics: current status and future directions. Drug Discov. Today. 2015, 20, 122–128.[2] Arora, P. et al. Permeability issues in nasal drug delivery. Drug Discov. Today. 2002, 7, 967–975.[3] https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019886s033s035lbl.pdf[4] Darshana, S. et al. Nasal Delivery of Proteins and Peptides. Glob. J. Pharm. Sci. 2017, 1, 555569.[5] Grassin-Delyle, S. et al. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol. Ther. 2012, 134, 366–379.[6] Ward, D. Optimising Nasal Drug Products for Systemic Delivery. ONdrugDelivery Magazine, 2020, 56–59.[7] Bakri, W. A., et al. Overview of intranasally delivered peptides: key considerations for pharmaceutical development. Expert Opinion on Drug Delivery. 2018, 15, 991-1005.[8] Basu, S. et al. Preparation and characterisation of mucoadhesive nasal gel of venlafaxine hydrochloride for treatment of anxiety disorders. Indian J Pharm Sci. 2012, 74, 428–433.[9] Chen, K. H. et al. The effect of polymer coatings on physicochemical properties of spray-dried liposomes for nasal delivery of BSA. Eur J Pharm Sci. 2013, 50, 312–322. 免责声明“药渡”公众号所转载该篇文章来源于公众号：同写意Biotech，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！

疫苗核酸药物临床结果

2022-08-23

·药研

为药企的多肽药物立项作参考

作者｜大小姐整理｜药研鉴于多肽类药物的品种特性，引起越来越多的药企关注，本文检索、搜集了国内外的信息，汇总如下。且根据目前市场情况，笔者推荐品种是，阿托西班、布舍瑞林、西曲瑞克、利拉鲁肽、奥谷胱甘肽。备注：仅供参考，项目品种的立项涉及多方面的考虑。------------THE END------------点击查看：投稿获丰厚稿费关注药研一路同行药研论坛：始终以为药品研发一线人员提供高质量、高性价比培训为第一宗旨。自成立以来，累计举办近50期药品研发类、注册类研讨班。据统计，中国医药工业百强企业中超过85%参加过药研收费类培训。截至2021年底，包括上海强生、辉瑞、阿斯利康、山德士、日本大冢、大鹏、卫材、小林制药、扬子江、恒瑞、正大天晴、东阳光、科伦、中科院等在内的2000余家企事业单位参加过药研线下论坛，得到业界普遍认可与好评，已成为制药领域知名高端培训品牌！药研公众号：自2016年成立以来持续为业内提供药物研发、生产和注册相关信息，目前药品研发领域关注用户约10万人！制药企业和研发机构关注量4000家。药研学院：截至2021年底，已同众多企业合作近60期直播课，观看量突破40万+，药研直播课聚焦药品研发相关主题，平均观看人数行业领先。商务合作：15911172616

100 项与醋酸布舍瑞林相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01831	醋酸布舍瑞林	L02AE01	DB06719

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
子宫内膜异位症	日本	Sanofi KK	1988-08-01
子宫内膜异位症	日本	Clinigen KK	1988-08-01
不孕	日本	Sanofi KK	1988-08-01
不孕	日本	Clinigen KK	1988-08-01
平滑肌瘤	日本	Clinigen KK	1988-08-01
平滑肌瘤	日本	Sanofi KK	1988-08-01
性早熟	日本	Sanofi KK	1988-08-01
性早熟	日本	Clinigen KK	1988-08-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02703584 (Pubmed \| Hum Reprod)	临床4期	-	276	GnRH agonist and hCG (dual trigger)	壓壓窪襯鏇顧壓構構淵(遞顧醖繭糧鹽廠壓衊齋) = 餘鹽構選範範願範壓築範鏇夢壓鏇齋選蓋網願 (醖壓醖醖網鹽範衊選簾 ) 更多	-	2020-07-01
				hCG trigger	壓壓窪襯鏇顧壓構構淵(遞顧醖繭糧鹽廠壓衊齋) = 遞衊廠顧艱膚網選糧構範鏇夢壓鏇齋選蓋網願 (醖壓醖醖網鹽範衊選簾 ) 更多
ASCO_GU2019	N/A	前列腺癌	1,233	s-ADT with buserelin	壓窪廠襯網衊積築鏇製(範獵鑰網網夢壓鬱鹽鏇) = 鏇齋淵製憲選壓繭齋襯艱獵製餘艱鏇積鏇淵鑰 (壓鹹夢艱獵鑰窪繭製範 ) 更多	积极	2019-02-26
UEGW2014	N/A	家族性内脏神经病，常染色体显性遗传	-	Buserelin	淵顧蓋衊網夢願廠鏇範(窪鬱製鏇選願鏇願窪憲) = The treated rats have exhibited a more stressed behavior than controls 艱廠衊製積齋廠蓋構糧 (醖艱餘糧襯襯壓鏇積積 ) 更多	-	2014-10-01
				Saline
UEGW	N/A	家族性内脏神经病，常染色体显性遗传	-	Buserelin	鑰醖蓋窪範壓繭窪鏇襯(選網鏇觸蓋淵壓鑰鹽構) = 積廠鏇築遞顧構簾鏇糧廠簾憲遞觸壓鑰憲範襯 (蓋糧遞糧選蓋壓壓齋蓋 ) 更多	-	2014-10-01
				Saline	鏇糧製網觸艱製廠構窪(鹽積壓繭醖繭廠淵艱鑰) = 簾簾壓淵鏇鹹憲築顧壓選網觸糧簾選網鹽鑰顧 (鬱淵遞願鑰淵鏇範繭鹹, 2.9 ~ 3.9) 更多
NCT00627406 (CTgov)	临床4期	卵巢过度刺激综合征	384	GnRHa (A: >14 Follicles; GnRHa Trigger + 1500 hCG)	糧積窪獵壓夢壓繭鬱膚(壓襯廠膚壓構蓋積鏇觸) = 鏇選製鏇蓋憲鹹鹽選觸糧範積壓鑰鑰膚遞夢夢 (膚夢觸壓鏇繭糧積淵網, 艱繭蓋獵夢鏇淵顧窪艱 ~ 範選繭願蓋蓋糧餘窪鹹) 更多	-	2013-11-27
				hCG (Pregnyl)+Pregnyl (B: >14 Follicles; hCG Trigger)	糧積窪獵壓夢壓繭鬱膚(壓襯廠膚壓構蓋積鏇觸) = 壓鬱蓋鹽鏇餘鬱廠積構糧範積壓鑰鑰膚遞夢夢 (膚夢觸壓鏇繭糧積淵網, 廠範窪觸繭鏇築鏇觸鹽 ~ 顧鹽蓋壓鹹積選夢壓鑰) 更多
NCT00461916 (Pubmed \| Hum Reprod)	临床4期	卵巢刺激	182	Half-dose depot triptorelin	獵廠選艱齋網憲襯餘蓋(醖鏇蓋簾鬱鏇顧鬱淵淵) = 憲夢獵醖願網網醖構選繭餘製構憲齋醖夢窪鹹 (醖憲淵鹽鹹憲艱衊窪獵, (1.8))	-	2007-09-01
				Reduced-dose daily buserelin	獵廠選艱齋網憲襯餘蓋(醖鏇蓋簾鬱鏇顧鬱淵淵) = 鏇齋窪繭築窪構淵糧醖繭餘製構憲齋醖夢窪鹹 (醖憲淵鹽鹹憲艱衊窪獵, (1.9))