A Phase 1 Open-label, Multi-center Study of the Safety, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS)

A Phase 1 Open-label, Multi-center Study of the Safety, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML), or with Relapsed/refractory, High-risk Myelodysplastic Syndrome (MDS)

开始日期2022-12-12

申办/合作机构

PureTech Health Plc

NCT04666688 / Recruiting临床1/2期

A Phase 1/2 Open-label, Multi-center Study of the Safety, Pharmacokinetics, and Anti-tumor Activity of LYT-200 as a Single Agent and in Combination With Chemotherapy or Tislelizumab in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase 1/2 Open-label, Multi-center Study of the Safety, Pharmacokinetics, and Anti-tumor Activity of LYT-200 Alone and in Combination with Chemotherapy or Tislelizumab in Patients with Metastatic Solid Tumors

开始日期2020-12-15

申办/合作机构

Pure Technologies Ltd.

100 项与 LYT-200 相关的临床结果

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100 项与 LYT-200 相关的转化医学

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100 项与 LYT-200 相关的专利（医药）

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项与 LYT-200 相关的文献（医药）

2023-09-01·Small (Weinheim an der Bergstrasse, Germany)

PEG-Sheddable Nanodrug Remodels Tumor Microenvironment to Promote Effector T Cell Infiltration and Revise Their Exhaustion for Breast Cancer Immunotherapy.

Article

作者: Yi, Jing ; Huang, Tao ; Wang, Rongze ; Tu, Mei ; Wang, Yong ; Zhang, Zekun ; Luo, Pin ; Zhang, Qiaoyun ; Zeng, Rong

Low infiltration of cytotoxic T lymphocytes and their exhaustion manifest the two concurrent main hurdles for achieving effective tumor immunotherapy of triple-negative breast cancer. It is found that Galectin-9 blockage can revise the exhaustion of effector T cells, meanwhile the repolarization of protumoral M2 tumor-associated macrophages (TAMs) into tumoricidal M1-like ones can recruit effector T cells infiltrating into tumor to boost immune responses. Herein, a sheddable PEG-decorated and M2-TAMs targeted nanodrug incorporating Signal Transducer and Activator of Transcription 6 inhibitor (AS) and anti-Galectin-9 antibody (aG-9) is prepared. The nanodrug responds to acidic tumor microenvironment (TME) with the shedding of PEG corona and the release of aG-9, exerting local blockade of PD-1/Galectin-9/TIM-3 interaction to augment effector T cells via exhaustion reversing. Synchronously, targeted repolarization of M2-TAMs into M1 phenotype by AS-loaded nanodrug is achieved, which promotes tumor infiltration of effector T cells and thus synergizes with aG-9 blockade to boost the therapeutic efficacy. Besides, the PEG-sheddable approach endows nanodrug with stealth ability to reduce immune-related adverse effects caused by AS and aG-9. This PEG sheddable nanodrug holds the potential to reverse the immunosuppressive TME and increase effector T cell infiltration, which dramatically enhances immunotherapy in highly malignant breast cancer.

2023-07-31·International journal of molecular sciences

Antiretroviral Treatment-Induced Galectin-9 Might Impact HIV Viremia in Addition to Contributing to Inflammaging.

Article

作者: Wagh, Vaishnav ; Shete, Ashwini ; Shidhaye, Pallavi ; Sawant, Jyoti ; Ghate, Manisha ; Kulkarni, Smita ; Sane, Suvarna ; Rao, Amrita

BACKGROUND:

Galectin-9 induces HIV reactivation and also contributes to non-AIDS events through inflammaging. Hence, it is important to assess its levels in HIV-infected individuals to determine their association with HIV viremia and other comorbidities.

METHODS:

Plasma galectin-9 levels were estimated in viremic (n = 152) and aviremic (n = 395) individuals on first-line antiretroviral therapy (ART). They were assessed for correlation with HIV-1 viral load (VL), CD4 count, and ART duration, as well as for receiver operating characteristic curve analysis.

RESULT:

Plasma galectin-9 levels correlated positively with VL (r = 0.507, p < 0.0001) and ART duration (r = 0.308, p = 0.002) and negatively with CD4 count (r = -0.186, p < 0.0001). Area under the curve for galectin-9/CD4 count ratio for identifying viremic individuals was 0.906. Sensitivity and specificity of the ratio at a cutoff of 14.47 were 90.13% and 70.05%, respectively, for detecting viremic individuals. Further, galectin-9 levels correlated with cystatin C (r = 0.239, p = 0.0183), IL-18 (r = 0.311, p = 0.006), and systolic blood pressure (r = 0.220, p = 0.0355). Galectin-9-induced HIV reactivation was significantly lower in individuals on long-term ART than those on short-term ART.

CONCLUSION:

The galectin-9-to-CD4 count ratio indicated the potential of galectin-9 as a cheaper monitoring tool to detect HIV viremia. Strategies for countering the effects of galectin-9 for controlling HIV viremia and non-AIDS events are urgently warranted.

2023-05-29·Biomolecules

Chimera and Tandem-Repeat Type Galectins: The New Targets for Cancer Immunotherapy.

Review

作者: Lee, Ka Wai ; Ho, James Chung Man ; Yan, Sheng ; Lam, Sze Kwan ; Ko, Frankie Chi Fat

In humans, a total of 12 galectins have been identified. Their intracellular and extracellular biological functions are explored and discussed in this review. These galectins play important roles in controlling immune responses within the tumour microenvironment (TME) and the infiltration of immune cells, including different subsets of T cells, macrophages, and neutrophils, to fight against cancer cells. However, these infiltrating cells also have repair roles and are hijacked by cancer cells for pro-tumorigenic activities. Upon a better understanding of the immunomodulating functions of galectin-3 and -9, their inhibitors, namely, GB1211 and LYT-200, have been selected as candidates for clinical trials. The use of these galectin inhibitors as combined treatments with current immune checkpoint inhibitors (ICIs) is also undergoing clinical trial investigations. Through their network of binding partners, inhibition of galectin have broad downstream effects acting on CD8⁺ cytotoxic T cells, regulatory T cells (Tregs), Natural Killer (NK) cells, and macrophages as well as playing pro-inflammatory roles, inhibiting T-cell exhaustion to support the fight against cancer cells. Other galectin members are also included in this review to provide insight into potential candidates for future treatment(s). The pitfalls and limitations of using galectins and their inhibitors are also discussed to cognise their clinical application.

项与 LYT-200 相关的新闻（医药）

2024-04-11

·BioSpace

PureTech Receives FDA Fast Track Designation for LYT-200 in Head and Neck Cancers

LYT-200 is being evaluated in locally advanced/metastatic solid tumors, including head and neck cancers, as well as in hematological malignancies, such as acute myeloid leukemia and high-risk myelodysplastic syndrome Phase 1b and Phase 1/2 clinical trials of LYT-200 ongoing BOSTON--(BUSINESS WIRE)-- PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, today announced that the U.S. Food and Drug Administration (“FDA”) has granted Fast Track designation for LYT-200 in combination with anti-PD1 therapy for the treatment of recurrent/metastatic head and neck squamous cell carcinomas (“head and neck cancers”). “In the U.S., there are approximately 66,000 people diagnosed with head and neck cancers each year, and the prognosis for metastatic disease is unfavorable, with a median survival rate of about ten months,” said Eric Sherman, M.D., Memorial Sloan Kettering Cancer Center and an investigator in PureTech’s Phase 1/2 clinical trial. “There is an important need to explore promising new mechanisms and targets such as galectin-9 to bring therapeutic innovation to this patient population.” LYT-200 is an antibody against galectin-9, a potent cancer driver, and is the most advanced clinical program against this target. It is being evaluated in two ongoing clinical trials: a Phase 1/2 adaptive design trial in advanced/metastatic solid tumors, including head and neck cancers. In this trial, LYT-200 is being evaluated as a monotherapy and in combination with tislelizumab, an anti-PD-1 antibody developed by BeiGene. LYT-200 has demonstrated a favorable safety pro all cohorts, including the monotherapy and combination arms with BeiGene’s tislelizumab, and shown disease control and suggestions of initial anti-tumor activity. a Phase 1b clinical trial evaluating LYT-200 as a monotherapy and in combination with venetoclax and hypomethylating agents in hematological malignancies, including acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome. LYT-200 has demonstrated a favorable safety and tolerability pro well as early signals of potential clinical activity. “By granting Fast Track designation to LYT-200 for head and neck cancers, the FDA continues to highlight areas of critical need within oncology as well as the potential for LYT-200,” said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech. “As galectin-9’s role in suppressing immune-mediated activity has been well-validated, it represents an important area of clinical research, especially in aggressive cancers with increased mortality.” Fast Track designation is a process designed to streamline the development and accelerate the assessment of drugs that target serious conditions with unmet medical need. The FDA has also granted orphan drug designation to LYT-200 for the treatment of AML. About LYT-200 LYT-200 is a fully human IgG4 monoclonal antibody targeting galectin-9 for the potential treatment of locally advanced/metastatic solid tumors that have poor survival rates, including head and neck cancers. It is also in development for the treatment of hematological malignancies, such as acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Galectin-9 is a potent oncogenic driver and immunosuppressor, and in AML it has been described to work via engagement with cytotoxic CD8 T cells and natural killer cells. A wide variety of preclinical data underscores the importance of galectin-9 as a target and suggests a potential opportunity for biomarker development. These data demonstrate high expression of galectin-9 across various blood cancers and solid tumor types and show that galectin-9 levels correlate with poor survival in several cancers. LYT-200 has demonstrated direct cytotoxic, anti-leukemic effects through multiple mechanisms, as well as synergy with standard of care chemotherapy and venetoclax in preclinical models. Consistent with its hub-and-spoke model, PureTech intends to advance LYT-200 via its Founded Entity Gallop Oncology. About PureTech Health PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech's R&D engine has resulted in the development of 28 therapeutics and therapeutic candidates, including two that have received both U.S. FDA clearance and European marketing authorization and a third (KarXT) that has been filed for FDA approval. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points. For more information, visit or connect with us on X (formerly Twitter) @puretechh. Cautionary Note Regarding Forward-Looking Statements This press release contains statements that are or may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those related to the LYT-200 development program and the timing for results from ongoing clinical trials of LYT-200, and our future prospects, developments, and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2022 filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise. View source version on businesswire.com: Contacts PureTech Public Relations publicrelations@puretechhealth.com Investor Relations IR@puretechhealth.com UK/EU Media Ben Atwell, Rob Winder +44 (0) 20 3727 1000 puretech@fticonsulting.com US Media Nichole Bobbyn +1 774 278 8273 nichole@tenbridgecommunications.com Source: PureTech Health plc View this news release online at:

临床1期快速通道孤儿药

2024-03-13

·Business Wire

PureTech Receives Orphan Drug Designation for LYT-200 in Acute Myeloid Leukemia

BOSTON--( BUSINESS WIRE )-- PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to LYT-200 for the treatment of AML. “ The current long-term survival rates of patients with relapsed or refractory AML are very poor, and there remains a tremendous unmet need for more effective therapies,” said Amir Fathi, MD, Director of the Leukemia Program at Massachusetts General Hospital and lead investigator of the trial. LYT-200 is a fully human IgG4 monoclonal antibody (mAb) targeting galectin-9, a potent oncogenic driver in leukemia cells and an immunosuppressive protein. LYT-200 has demonstrated direct cytotoxic, anti-leukemic effects through multiple mechanisms and is being developed as a potential novel treatment for hematological malignancies, such as relapsed/refractory AML and high-risk MDS, as well as locally advanced/metastatic solid tumors that have poor survival rates, including head and neck cancers. LYT-200 is currently being evaluated in an ongoing Phase 1b clinical trial in relapsed/refractory AML and MDS, both as a single agent and in combination with standard-of-care venetoclax and hypomethylating agents (HMA). Initial findings from this trial were announced in 2023 , and additional data are expected to be presented in a scientific forum in 2024. “ Orphan drug designation from the FDA validates our belief that targeting galectin-9 with LYT-200 is a novel, promising approach that may offer patients a better tolerated, more effective treatment,” notes Aleksandra Filipovic, MD, PhD, Head of Oncology at PureTech. The FDA grants orphan drug designation to novel drug and biologic products for the treatment, diagnosis, or prevention of conditions affecting fewer than 200,000 persons in the U.S. Orphan drug designation qualifies PureTech for incentives under the Orphan Drug Act, including tax credits for some clinical trials and eligibility for seven years of market exclusivity in the U.S., if the drug is approved for AML. About LYT-200 LYT-200 is a fully human IgG4 monoclonal antibody targeting galectin-9 for the potential treatment of hematological malignancies, such as acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), as well as locally advanced/metastatic solid tumors that have poor survival rates, including head and neck cancers. Galectin-9 is a potent oncogenic driver and immunosuppressor, and in AML it has been described to work via cytotoxic CD8 T cells and natural killer cells. A wide variety of preclinical data underscores the importance of galectin-9 as a target and suggests a potential opportunity for biomarker development. These data demonstrate high expression of galectin-9 across various blood cancers and solid tumor types and show that galectin-9 levels correlate with poor survival in several cancers. LYT-200 has demonstrated direct cytotoxic, anti-leukemic effects through multiple mechanisms, as well as synergy with standard of care chemotherapy and venetoclax in preclinical models. In the ongoing, Phase 1b clinical trial evaluating LYT-200 as a single agent in AML and MDS, LYT-200 has demonstrated a favorable safety and tolerability profile as well as early signals of potential clinical activity. This trial is ongoing, in addition to a Phase 1/2 adaptive design trial for the potential treatment of advanced/metastatic solid tumors. Consistent with its hub-and-spoke model, PureTech intends to advance LYT-200 via its Founded Entity Gallop Oncology. About PureTech Health PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech's R&D engine has resulted in the development of 28 therapeutics and therapeutic candidates, including two (Plenity ® and EndeavorRx ® ) that have received both US FDA clearance and European marketing authorization and a third (KarXT) that has been filed for FDA approval. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points. For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh. Cautionary Note Regarding Forward-Looking Statements This press release contains statements that are or may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those related to the LYT-200 development program and the timing for results from ongoing clinical trials of LYT-200, and our future prospects, developments and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2022 filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.

临床1期孤儿药临床结果临床申请

2024-03-11

·BioSpace

FibroGen Appoints Deyaa Adib, M.D. as Chief Medical Officer

SAN FRANCISCO, March 11, 2024 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ: FGEN) today announced the appointment of Deyaa Adib, M.D., an executive leader with almost three decades of oncology development experience, as Senior Vice President & Chief Medical Officer to oversee all global clinical development activities. The appointment is effective March 11, 2024. “Deyaa’s leadership and expertise in oncology research and clinical development, particularly in bringing oncology therapeutics to market, will be key to accelerating our oncology pipeline and bringing novel cancer therapies to patients in need,” said Thane Wettig, Chief Executive Officer of FibroGen. “We are excited to welcome him to FibroGen during this critical time as we prepare for two pivotal read-outs for pamrevlumab in pancreatic cancer, advance Phase 2 planning for FG-3246 in metastatic castration-resistant prostate cancer, IND for our anti-Galectin-9 antibody and continue IND-enabling work for our anti-CCR8 antibody,” he added. “We will benefit immensely from Deyaa’s broad and deep experience in oncology drug development, including his experiences in both pancreatic and prostate cancers.” “I am excited to join FibroGen and lead the clinical development organization at this important time for our company,” commented Deyaa Adib, M.D., Chief Medical Officer of FibroGen. “I look forward to working with such a highly talented and deeply experienced group of colleagues as we progress our oncology pipeline with the goal to bring valuable medicines to cancer patients with significant unmet medical need." Dr. Adib, a seasoned industry leader, has over 27 years of medical oncology experience in the biotechnology and pharmaceutical industries, including seven successful registrations across solid tumor and hematologic malignancy indications. Prior to joining FibroGen, he was the Chief Medical Officer of Triumvira Immunologics Inc. where he led the transition of two novel cell therapy programs into clinical development. He previously served as Acting Chief Medical Officer at Rain Therapeutics, and as Vice President of late-stage development at Blueprint Medicines, where he led the development of avapritinib which is currently approved for gastrointestinal stromal tumors and advanced systemic mastocytosis. Dr. Adib also served as Global Therapeutics Head for solid tumors at Baxalta, in-licensing and advancing the development of nanoliposomal irinotecan that was subsequently approved globally for pancreatic cancer, establishing a new standard of care in the second line metastatic setting. He also served as Head of Hematologic Malignancies at ARIAD Pharmaceuticals, leading the global clinical program for ponatinib in chronic myeloid leukemia. Earlier in his career, Dr. Adib held multiple oncology clinical development leadership positions at Aventis, Sanofi and Astellas Pharma, advancing the development of Taxotere in prostate cancer, breast cancer and gastric cancer, oxaliplatin in colorectal cancer and notably enzalutamide, which led to a treatment paradigm shift in prostate cancer. He has served as a scientific advisory board member for multiple biotech companies and provided strategic consulting support to several cell therapy startups. Dr. Adib obtained an M.B., B.Ch. degree from Cairo University School of Medicine in Cairo, Egypt. He completed his postgraduate medical oncology training at the Anglo-American Cancer Institute in Cairo and additionally at Tufts University School of Medicine, Boston, MA, in clinical pharmacology, drug development and regulation. About FibroGen FibroGen, Inc. is a biopharmaceutical company focused on accelerating the development of novel therapies at the frontiers of cancer biology. Pamrevlumab, an anti-CTGF fully human monoclonal antibody, is in clinical development for the treatment of metastatic pancreatic cancer and locally advanced unresectable pancreatic cancer (LAPC). Roxadustat (爱瑞卓®, EVRENZOTM) is currently approved in China, Europe, Japan, and numerous other countries for the treatment of anemia in chronic kidney disease (CKD) patients on dialysis and not on dialysis. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted for review by the China Health Authority. FibroGen recently expanded its research and development portfolio to include antibody-drug conjugate (ADC) and immunoncology product candidates for the treatment of solid tumors. For more information, please visit . Forward-Looking Statements This release contains forward-looking statements regarding FibroGen’s strategy, future plans and prospects, including statements regarding its clinical programs and those of its partner, PanCAN. These forward-looking statements include, but are not limited to, statements regarding the potential and probability of success of FibroGen product candidates, and statements about FibroGen’s plans and objectives and typically are identified by use of terms such as “may,” “will”, “should,” “on track,” “could,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue” and similar words, although some forward-looking statements are expressed differently. FibroGen’s actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties related to the continued progress and timing of its various programs, including the enrollment and results from ongoing and potential future clinical trials, and other matters that are described in FibroGen’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, as filed with the Securities and Exchange Commission (SEC), including the risk factors set forth therein. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and FibroGen undertakes no obligation to update any forward-looking statement in this press release, except as required by law. Contacts: FibroGen, Inc. Investors: David DeLucia, CFA Vice President of Corporate FP&A / Investor Relations ddelucia@fibrogen.com Media: Meichiel Keenan Director, Investor Relations and Corporate Communications mkeenan@fibrogen.com

高管变更上市批准临床1期临床2期免疫疗法

100 项与 LYT-200 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
结直肠癌	临床2期	美国	Pure Technologies Ltd.	2020-12-15
头颈部肿瘤	临床2期	美国	Pure Technologies Ltd.	2020-12-15
肿瘤转移	临床2期	美国	Pure Technologies Ltd.	2020-12-15
胰腺癌	临床2期	美国	Pure Technologies Ltd.	2020-12-15
膀胱尿路上皮癌	临床2期	美国	Pure Technologies Ltd.	2020-12-15
急性髓性白血病	临床1期	美国	PureTech Health Plc	2022-12-12
骨髓增生异常综合征	临床1期	美国	PureTech Health Plc	2022-12-12

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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


NCT04666688 (ESMO_IO2023)	临床1/2期	-	20	LYT-200	選鏇願醖鑰積顧淵製構(顧製鬱鹹築鹹齋獵選範) = 齋鏇簾餘網製鑰製齋願衊蓋鏇夢壓鬱餘齋蓋襯 (壓齋網獵膚遞膚願餘膚 )	-	2023-12-07
				LYT-200 + TIS	選鏇願醖鑰積顧淵製構(糧齋鏇衊鹽鑰鹽選願觸) = 淵淵夢蓋構獵夢構衊壓餘壓鑰築齋鏇選衊顧鬱 (製觸廠鹹構醖窪鏇鹽醖 )