Clinical study to investigate safety, tolerability, efficacy,pharmacokinetics and pharmacodynamics of inhaled multiple doses of the human GATA-3-specific DNAzyme solution SB010 in patients with moderate to severe COPD– A randomised, double-blind, parallel group, multicenter, phase IIa pilot study – - SB010-COPD

开始日期2014-07-15

申办/合作机构

Philipps University of Marburg

EUCTR2013-004599-36-DE

/ Not yet recruiting临床2期

SB012 for the treatment of active ulcerative colitis (SECURE): a prospective, multi-centre, randomised, double-blind, placebo-controlled phase IIa clinical trial to evaluate the efficacy, pharmacokinetics, tolerability, and safety of SB012 enema administered once daily - SECURE

开始日期2014-04-23

申办/合作机构

sterna biologicals GmbH

NCT02129439

/ Completed临床1/2期

SB012 for Treatment of Active Ulcerative Colitis: Prospective Multi-centre Randomised Double-blind Placebo-controlled Phase IIa Clinical Trial to Evaluate Efficacy, Pharmacokinetics, Tolerability and Safety of SB012 Enema Administered OD

Ulcerative colitis (UC) represents one of the major entities of idiopathic inflammatory bowel diseases which are defined as chronically relapsing inflammations of the gastrointestinal tract not due to specific pathogens. It is characterised by a superficial, continuous mucosal inflammation, which predominantly affects the large intestine. The clinical course is typically marked by periods of asymptomatic remission punctuated by unpredictable recurrent attacks. The symptoms of the patients are marked by persistent diarrhoea with severe faecal urgency and often incontinence, rectal bleeding, abdominal cramping and weight loss.
Uncontrolled activation of mucosal effector T cells has been identified as the main pathogenic mechanism involved in the initiation and perpetuation of intestinal inflammatory reactions.
Patients with moderate UC are initially treated with mesalazine, applied both orally and rectally. If symptoms do not improve, systemic corticosteroids are to be administered. Patients who do not respond to systemic corticosteroids may become eligible for treatment with a calcineurin inhibitor or an anti-tumor necrosis factor (TNF)α antibody. Alternatively, patients may have to undergo major colorectal surgery.
Patients who do not adequately respond to these treatment strategies exhibit serious drawbacks. Colorectal surgery may result in a severely compromised quality of life.
Therefore, patients with moderate or severe UC may significantly benefit from new therapeutic alternatives.
The transcription factor GATA-3 is an interesting target for a novel therapeutic strategy in UC.
GATA-3 is the key regulation factor of Th2-driven immune responses. It is indispensable for the differentiation and activation of Th2 cells, integrates Th2 signals, and induces Th2 cytokine expression. Results of a recent clinical trial in children showed that GATA-3 is involved in the pathogenesis of the acute phase of UC.
The investigational product SB012 contains the DNAzyme hgd40 that targets GATA-3. By cleaving GATA-3 mRNA hgd40 reduces specific cytokine production and thereby reduces key features of mucosal inflammation.
DNAzymes are completely generated by chemical synthesis, not by use of any living organism and are therefore not biological drugs.
This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of the topical formulation SB012 available in a concentration of 7.5mg/ml hgd40 in 30ml PBS once daily as a ready-for-use enema in patients with active UC.

开始日期2014-04-01

申办/合作机构

sterna biologicals GmbH

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项与 Antisense oligonucleotide therapeutics(sterna) 相关的文献（医药）

2024-12-01·Journal of Hazardous Materials

Selenium increases antimony uptake in As-hyperaccumulators Pteris vittata and Pteris cretica by promoting antimonate reduction: GSH-GSSG cycle and arsenate reductases HAC1/ACR2

Article

作者: Ma, Lena Q ; Ma, Lena Q. ; Liu, Yi-Wen ; Zhou, Qian-Yu ; Li, Wei ; He, Si-Xue ; Liu, Chen-Jing

Selenium-enhanced arsenic uptake by As-hyperaccumulators Pteris vittata and Pteris cretica is known, but how it impacts antimony (Sb) uptake and associated mechanisms are unclear. Here, we investigated the effects of 2.5 μM selenate (Se_2.5) on Sb uptake by two plants after growing for 10 days under hydroponics containing 10 or 50 μM antimonate (SbV) (Sb₁₀ or Sb₅₀). Both plants were efficient in taking up SbV, which was reduced to SbIII (17-40 %) and mainly accumulated in the roots (86-97 %). The addition of Se increased the Sb contents by 78-97 and 29-33 % to 242-1358 and 132-697 mg kg^-1 in P. vittata and P. cretica roots. Compared with the Sb₁₀ and Sb₅₀ treatments, addition of Se increased the SbV reduction, with more increase in P. vittata than P. cretica roots (181-273 % vs. 17-29 %). Enhanced GSH-GSSG cycle mediated by glutathione peroxidase (GPX) and glutathione reductase (GR) may play an important role in SbV reduction in the roots. Compared with the Sb treatments, addition of Se increased the GPX and GR activity by 71-97 and 2-50 % in P. vittata roots, and 59-153 and 22-63 % in P. cretica roots. Besides, Se upregulated the expression of arsenate reductases PvHAC1 and PvACR2 in P. vittata roots by 1.7-3.4 folds but not in P. cretica. Se-enhanced SbV reduction in P. vittata explains why it was more effective in Sb accumulation than P. cretica. Taken together, Se is effective in increasing the Sb uptake in both plants probably by promoting SbV reduction via GSH-GSSG cycle and/or PvHAC1/PvACR2, suggesting that Se may be used to enhance phytostabilization of Sb-contaminated soils.

2023-01-01·Environmental Pollution

Efficacy of endophytic SB10 and glycine betaine duo in alleviating phytotoxic impact of combined heat and salinity in Glycine max L. via regulation of redox homeostasis and physiological and molecular responses

Article

作者: Bilal, Saqib ; Asaf, Sajjad ; Al-Harrasi, Ahmed ; Imran, Muhammad ; Shahzad, Raheem ; Lee, In-Jung

Adverse environmental stresses occurring simultaneously exhibit a lethal effect on crop productivity at the global level. Here, we investigated the individual and synergistic effects of endophytic T. virens SB10 and glycine betaine (GB) on the physiological and biochemical responses of Glycine max L. to alleviate the devastating effects of combined heat and salinity (HS) stress. Screening against HS stress tolerance showed that SB10 has significant tolerance against heat stress and produces hormones such as gibberellins and indole-3-acetic acid upon GB amendment of the growth medium under HS stress. Moreover, the current findings illustrated that the synergistic application of SB10 and GB was effective in alleviating the negative effects of HS stress on plant growth and physiology. The findings revealed that SB10 + GB led to a reduction in proline accumulation and Na⁺ uptake. It also maintained a high K⁺/Na ⁺ ratio by regulating GmHKT1 and GmSOS1 expression and enhanced macronutrient uptake (N, Ca, K) in plants. In turn, plants exhibited a higher growth rate and gaseous exchange attributes coupled with the upregulation of APX, SOD, POD, and GSH antioxidant activities and transcript accumulation of GmSOD1 and GmAPX1 to overcome HS-induced oxidative damage. Furthermore, SB10 + GB downregulated DREB2, DREB1B, and GmNCED3 expression and resulted in the reduced accumulation of endogenous ABA while enhancing endogenous SA accumulation via upregulation of PAL genes. In addition, enhanced accumulation of bioactive gibberellins (GA1, GA3, GA4, and GA7) was detected under HS stress in the SB10 + GB treatment group. Moreover, SB10 + GB also significantly regulated GmHsp90A2 and GmHsfA2 expression in tolerance against HS stress. The combination of SB10 and GB was shown to be an effective and alternative approach for growing G. max at high temperature coupled with saline conditions for sustainable agriculture.

2018-12-01·Respiratory Research2区 · 医学

A GATA3-specific DNAzyme attenuates sputum eosinophilia in eosinophilic COPD patients: a feasibility randomized clinical trial

2区 · 医学

ArticleOA

作者: Renz, Harald ; Greulich, Timm ; Renz, Jonas ; Watz, Henrik ; Klemmer, Andreas ; Lueer, Katrin ; Vogelmeier, Claus F ; Harnisch, Susanne ; Müller, Meike ; Homburg, Ursula ; Hohlfeld, Jens M ; Schade-Brittinger, Carmen ; Pedersen, Frauke ; Garn, Holger ; Kirsten, Anne ; Neuser, Petra

BACKGROUNDA subset of COPD-patients presents with eosinophilic airway inflammation. While treatment of asthmatic patients with the GATA3-specific DNAzyme SB010 attenuated sputum eosinophilia after allergen challenge, this specific treatment has not been evaluated in patients with COPD. Our objective was to evaluate the feasibility and safety of inhaled SB010 in COPD patients with sputum eosinophilia.METHODSWe conducted a randomized, double-blind, placebo-controlled, multicentre clinical trial in COPD-patients with sputum eosinophilia (≥2.5% non-squamous cells). Patients inhaled 10 mg SB010 bid or matching placebo via the controlled inhalation system AKITA2 APIXNEB for 28 days. Endpoints included the feasibility of the study (primary), patient's safety, sputum eosinophils, F_ENO, lung function, symptoms, and biomarkers. The study was registered in the German Clinical Trials Register: DRKS00006087.RESULTSOne hundred thirty patients were screened, 23 patients were randomized (FEV₁ 49.4 ± 11.5%; sputum eosinophils 8.0 ± 8.4%) and 19 patients completed the study (10 placebo, 9 SB010. After 28 days, SB010 decreased the relative sputum eosinophil count (p = 0.004) as compared to no changes in placebo-treated patients. F_ENO, lung function, and symptoms were not affected significantly. We found an increase in blood IFN-γ (p = 0.02) and a trend to lower IL-5 levels in patients treated with SB010. SB010 was safe and well tolerated. Thirty five AEs (22 SB010, 13 placebo including 1 SAE) were observed with 3 AEs in each group judged to be possibly treatment-related.CONCLUSIONIn patients with eosinophilic COPD, sputum eosinophils could be reduced by inhalation of SB010. Long-term studies are needed to demonstrate clinical efficacy.

项与 Antisense oligonucleotide therapeutics(sterna) 相关的新闻（医药）

2023-03-02

·PRNewswire

Propulsion of Asthma Pipeline as Novel and Extensive 95+ Therapies Likely to Enter in the Treatment Domain | DelveInsight

Asthma is a chronic disease that affects a substantial number of patients worldwide, including children, a number of pharmaceutical companies are involved in developing drugs for asthma. This involvement includes the development of novel therapies that being evaluated in different phases of development. LAS VEGAS, March 2, 2023 /PRNewswire/ -- DelveInsight's ' Asthma Pipeline Insight – 2023 ' report provides comprehensive global coverage of available, marketed, and pipeline asthma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the asthma pipeline domain. Key Takeaways from the Asthma Pipeline Report DelveInsight's asthma pipeline report depicts a robust space with 90+ active players working to develop 95+ pipeline therapies for asthma treatment. Key asthma companies such as Mabpharm Limited, Avillion LLP, GlaxoSmithKline, Immunotek SL, AB Science, AstraZeneca, Inmunotek, Sterna Biologics, Verona Pharma, MediciNova, Foresee Pharmaceuticals, T-Balance Therapeutics, Teva Pharmaceutical Industries, Aldeyra Therapeutics, Trio Medicines, AstraZeneca, Cumberland Pharmaceuticals, Concentrx Pharmaceuticals, Tetherex Pharmaceuticals, SolAeroMed, Palobiofarma, Sanofi, Oneness Biotech, Novartis, Keymed Biosciences, Suzhou Connect Biopharmaceuticals, 4D Pharma Plc, Hoffman-La-Roche, Celltrion, Glenmark Pharmaceuticals, Archivel Farma, Siolta Therapeutics, Areteia Therapeutics, TFF Pharmaceuticals, Evelo Biosciences, Sunshine Guojian Pharmaceutical, Mabwell (Shanghai) Bioscience, Kinaset Therapeutics, Akari Therapeutics, KLUS Pharma, Upstream Bio, LEO Pharma, and others are evaluating new asthma drugs to improve the treatment landscape. Promising asthma pipeline therapies in various stages of development include CMAB007, PT027, GSK3511294, MM09-MG01, Masitinib, Budesonide/Formoterol, BGF MDI, MM09, PT001, SB010, Ensifentrine, Bedoradrine, FP-025, XC8, Tregalizumab, TEV-53275, TEV-48574, ADX-629, TR4, MEDI 3506, Lumicitabine, Ifetroban, Halix(TM) Albuterol, SelK2, S1226, PBF-680, Rilzabrutinib, FB825, FB704A, Dexpramipexole, CSJ117, CM310, CJM112, CBP-201, MRx-4DP0004, RG6314, CT-P39, GBR 310, RUTI, STMC-103H, Voriconazole Inhalation Powder, EDP1867, 610, 9MW1911, KN-002, Nomacopan, A378, Anti mIgE+B-cell, and others. In February 2023, UK's Medicines and Healthcare products Regulatory Agency (MHRA) granted an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) to dexpramipexole, an eosinophil lowering small molecule, that has recently entered Phase III clinical development. Dexpramipexole is beig developed by Areteia Therapeutics to inhibit the maturation and release of eosinophils in bone marrow, based on evidence from cell cultures and human biopsies, thereby lowering peripheral blood eosinophil levels. In February 2023, Pulmatrix, Inc. announced that the first patient dosed in a Phase IIb trial evaluating safety and efficacy of PUR1900 in subjects with Allergic Bronchopulmonary Aspergillosis (ABPA) and asthma. PUR1900 is the company's iSPERSE-enabled dry powder formulation of itraconazole, developed for inhaled pulmonary delivery. The Phase II trial is designed as a randomized, double-blind, multi-center, placebo-controlled study to evaluate the efficacy and duration of treatment with itraconazole, administered as a dry powder for inhalation (PUR1900). Endpoints include safety, tolerability, and potential efficacy outcomes in adult patients with asthma and ABPA. Olatec Therapeutics LLC in February 2023 completed the $40 million Series A round financing, the final closing of which was led by Sanders Morris Harris ("SMH"). Participation in the round came from both existing investors as well as new investors identified by each of Sanders Morris Harris, Advection Growth Capital, and the Company. Proceeds will be principally used to advance Olatec's lead compound, dapansutrile, into later-stage clinical development. Dapansutrile has also been observed to have anti-inflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models, including arthritis, asthma, acute myocardial infarction (AMI), heart failure, contact dermatitis, multiple sclerosis, melanoma, pancreatic and breast cancers, spinal cord injury (SCI), Parkinson's and Alzheimer's disease. In January 2023, Avillion LLP, announced that the US Food and Drug Administration (FDA) approved AstraZeneca's Airsupra (albuterol/budesonide, formerly known as PT027) for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in people with asthma aged 18 years and older. Airsupra is a first-in-class, pressurized metered-dose inhaler (pMDI), fixed-dose combination rescue medication containing albuterol, a short-acting beta2-agonist (SABA), and budesonide, an anti-inflammatory inhaled corticosteroid (ICS). Upstream Bio, in August 2022, initiated a Phase Ib multiple ascending dose study of UPB-101 in asthma patients and successful dosing of the first patient. UPB-101 is a monoclonal antibody designed to block the thymic stromal lymphopoietin receptor (TLSPR) and thus inhibit TSLP-driven inflammation. TSLP is a cytokine and a key driver of inflammatory response in asthma and other allergic and inflammatory diseases. Request a sample and discover the recent advances in asthma drug treatment @ Asthma Pipeline Report The asthma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage asthma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the asthma clinical trial landscape. Asthma Overview Asthma is a chronic disease of the airways. Asthma is characterized by airway inflammation and spasm. Airways are tubes that transport air into and out of the lungs. Asthmatics cause the inside walls of the airways to become sore and swollen. Because of inflammation and tightening of the muscles surrounding the small airways, the airways in the lungs become narrow. Asthma symptoms include coughing, wheezing, shortness of breath, and chest tightness. Asthma symptoms differ from person to person. A person may have infrequent asthma attacks, have symptoms only when exercising, or have symptoms all of the time. Asthma symptoms are similar to those of many respiratory infections. A careful clinical history is the first step in asthma diagnosis; identifying the characteristic symptoms and their duration, intensity, and relationship of symptoms with allergen and triggering agent; and the impact of these symptoms on quality of life. Find out more about drugs for asthma @ New Asthma Drugs A snapshot of the Asthma Pipeline Drugs mentioned in the report: Learn more about the emerging asthma pipeline therapies @ Asthma Clinical Trials Asthma Therapeutics Assessment The asthma pipeline report proffers an integral view of asthma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Asthma Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Parenteral, Intravenous, Subcutaneous, Topical Therapeutics Assessment By Molecule Type: Monoclonal Antibody, Peptides, Polymer, Small molecule, Gene therapy Therapeutics Assessment By Mechanism of Action: Immunomodulators, Beta 2 adrenergic receptor agonists; Glucocorticoid receptor agonists; Muscarinic receptor antagonists, Interleukin 5 receptor antagonists, Matrix metalloproteinase 12 inhibitors, Aldehyde inhibitors, Bacteria replacements; Microbiome modulators, Thymic stromal lymphopoietin inhibitors; Thymic stromal lymphopoietin modulators, Interleukin-33 inhibitors, Inflammasome inhibitors; Interleukin 1 beta inhibitors; Interleukin 18 inhibitors; Interleukin inhibitors; NLRP3 protein inhibitors, Interleukin-17 inhibitors Key Asthma Companies: Mabpharm Limited, Avillion LLP, GlaxoSmithKline, Immunotek SL, AB Science, AstraZeneca, Inmunotek, Sterna Biologics, Verona Pharma, MediciNova, Foresee Pharmaceuticals, T-Balance Therapeutics, Teva Pharmaceutical Industries, Aldeyra Therapeutics, Trio Medicines, AstraZeneca, Cumberland Pharmaceuticals, Concentrx Pharmaceuticals, Tetherex Pharmaceuticals, SolAeroMed, Palobiofarma, Sanofi, Oneness Biotech, Novartis, Keymed Biosciences, Suzhou Connect Biopharmaceuticals, 4D Pharma Plc, Hoffman-La-Roche, Celltrion, Glenmark Pharmaceuticals, Archivel Farma, Siolta Therapeutics, Areteia Therapeutics, TFF Pharmaceuticals, Evelo Biosciences, Sunshine Guojian Pharmaceutical, Mabwell (Shanghai) Bioscience, Kinaset Therapeutics, Akari Therapeutics, KLUS Pharma, Upstream Bio, LEO Pharma, and others. Key Asthma Pipeline Therapies: CMAB007, PT027, GSK3511294, MM09-MG01, Masitinib, Budesonide/Formoterol, BGF MDI, MM09, PT001, SB010, Ensifentrine, Bedoradrine, FP-025, XC8, Tregalizumab, TEV-53275, TEV-48574, ADX-629, TR4, MEDI 3506, Lumicitabine, Ifetroban, Halix(TM) Albuterol, SelK2, S1226, PBF-680, Rilzabrutinib, FB825, FB704A, Dexpramipexole, CSJ117, CM310, CJM112, CBP-201, MRx-4DP0004, RG6314, CT-P39, GBR 310, RUTI, STMC-103H, Voriconazole Inhalation Powder, EDP1867, 610, 9MW1911, KN-002, Nomacopan, A378, Anti mIgE+B-cell, and others. Dive deep into rich insights for new drugs for asthma treatment; visit @ Asthma Medications Table of Contents For further information on the asthma pipeline therapeutics, reach out @ Asthma Drug Treatment Related Reports Severe Asthma Market Severe Asthma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key severe asthma companies, including AstraZeneca, Novartis, Sanofi, among others. Asthma Pipeline Asthma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key asthma companies, including GSK, AstraZeneca, Teva Pharmaceuticals, among others. Severe Asthma Pipeline Severe Asthma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key severe asthma companies, including AstraZeneca, Novartis, Sanofi, among others. Chronic Obstructive Pulmonary Disease Epidemiology Forecast Chronic Obstructive Pulmonary Disease Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the chronic obstructive pulmonary disease epidemiology trends. Chronic Obstructive Pulmonary Disease Market Chronic Obstructive Pulmonary Disease Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key chronic obstructive pulmonary disease companies, including Sanofi, Chiesi Farmaceutici S.p.A., United Therapeutics Corporation, Verona Pharma, among others. Acute Respiratory Distress Syndrome Pipeline Acute Respiratory Distress Syndrome Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key acute respiratory distress syndrome companies, including Bayer, Faron Pharmaceuticals, BioMarck Pharmaceuticals, among others. 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It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Additionally, get in touch with our business executive to explore @ Healthcare Due Diligence Services Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

临床2期上市批准临床3期临床1期

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适应症	最高研发状态	国家/地区	公司	日期
中度特应性皮炎	临床2期	德国	sterna biologicals GmbH	2014-02-01
哮喘	临床2期	-	Philipps University of Marburg	-
哮喘	临床2期	-	Fraunhofer Item, Biomedical Research In Endstage And Obstructive Lung Disease Hannover (Breath), German Center For Lung Research (Hannover, Germany)	-
溃疡性结肠炎	临床2期	-	Philipps University of Marburg	-
溃疡性结肠炎	临床2期	-	Fraunhofer Item, Biomedical Research In Endstage And Obstructive Lung Disease Hannover (Breath), German Center For Lung Research (Hannover, Germany)	-
慢性阻塞性肺疾病	临床2期	-	Philipps University of Marburg	-
慢性阻塞性肺疾病	临床2期	-	Fraunhofer Item, Biomedical Research In Endstage And Obstructive Lung Disease Hannover (Breath), German Center For Lung Research (Hannover, Germany)	-
慢性阻塞性肺疾病	临床2期	-	sterna biologicals GmbH	-
轻度特应性皮炎	药物发现	德国	sterna biologicals GmbH	2014-02-01
过敏性哮喘	药物发现	德国	sterna biologicals GmbH	2012-12-01

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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


ERS2013	临床1期	过敏性哮喘 Th2-driven	24	SB010 5mg	衊鬱窪淵範選簾鏇衊願(簾廠鹽蓋淵蓋壓製鑰糧) = 製蓋遞壓餘築簾糧鏇糧蓋願積築夢簾蓋齋襯憲 (鹽願鬱獵製遞遞鏇鹹願 )	-	2013-09-01
ERS2013	临床1期	哮喘	108	SB010 0.4 mg	遞鏇構淵壓鏇壓獵膚繭(廠壓鹽窪鹹鏇艱築顧範) = 餘淵餘淵顧齋構艱糧艱製繭觸範淵艱鏇夢構製 (構糧衊顧衊餘築糧淵觸 )	积极	2013-09-01
ERS2013	临床1期	哮喘	108	SB010 40 mg	遞鏇構淵壓鏇壓獵膚繭(廠壓鹽窪鹹鏇艱築顧範) = 壓繭艱艱襯鹹觸願積膚製繭觸範淵艱鏇夢構製 (構糧衊顧衊餘築糧淵觸 )	积极	2013-09-01