HIV-1

已证明多硫酸戊聚糖可抑制 MT-4 细胞中的 HIV-1 活性，ED50 为 0.19 μg/mL。 4.0 μg/mL 的剂量即可完全抑制 HIV-1 抗原表达。它抑制 HUT-78 细胞中 HIV-1 抗原的表达，ED50 为 0.02 μg/mL[2]。 Pentosan polysulfate 可抑制 TNFα 的促炎作用，抑制 NF-κB，并减少由高葡萄糖和晚期糖基化终产物 (AGE) 诱导的 MCP-1 的产生 [3]。

在 5/6 肾切除大鼠中，多硫酸戊聚糖已被证明可以减少肾小球硬化和间质炎症。用多硫酸戊聚糖治疗可以保留肾功能，显着降低蛋白尿，并大大减轻肾脏病变，特别是肾小管间质炎症。在老年糖尿病肾脏中，多硫酸戊聚糖还可以减少促炎基因和 TNFα 的激活[3]。

Absorption, Distribution and Excretion
Slow
Sprague-Dawley rats were given (3)H-labelled pentosan orally or intravenously at a dose of 5 mg/kg bw, and killed 1 or 4 hours later, respectively. Autoradiography indicated extensive distribution of radiolabel in the whole animal after intravenous administration, with notable labelling of connective tissues, and low activity in bone and cartilage. There was a high concentration of radiolabel in the urine, and preferential localization of radiolabel to the lining of the urinary tract. After oral administration, the tissue distribution of radiolabel was similar, but activity was lower.
In rabbits given 1.0-1.2 mg pentosan by oral administration, median recovery in the urine was 7.45% (range, 2.1-46.0%) for pentosan of low relative molecular mass, and 0.1% (range, 0.0-0.3%) for pentosan of high relative molecular mass.
In rabbits given 1-1.2 mg of pentosan by intravenous administration, median recovery in the urine was 47.2% (range, 19.7-73.2%) for unfractionated pentosan, 74.6% (range, 31.4-96.3%) for pentosan of low relative molecular mass, and 3.3% (range, 2.5-5.0%) for pentosan of high relative molecular mass.
Excretion of pentosan was studied in 34 female patients with interstitial cystitis who were receiving long-term treatment with pentosan. The median concentration of pentosan in the urine of these patients was 1.2 ug/mL (range, 0.5-27.7 ug/mL). All the pentosan recovered from the urine of these patients was of low relative molecular mass.
For more Absorption, Distribution and Excretion (Complete) data for Elmiron (12 total), please visit the HSDB record page.

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Metabolism / Metabolites
Orally absorbed pentosan polysulfate sodium undergoes partial desulfation in the liver and spleen and partial depolymerization in the kidneys to form a large number of metabolites. Desulfation and depolymerization pathways can become saturated with continued dosing.
The fraction of pentosan polysulfate sodium that is absorbed is metabolized by partial desulfation in the liver and spleen, and by partial depolymerization in the kidney to a large number of metabolites. Both the desulfation and depolymerization can be saturated with continued dosing.

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Biological Half-Life
4.8 hours
Five healthy male volunteers were given (125)I-labelled pentosan in conjunction with unlabelled pentosan at a dose of 0.1, 1, 7, or 50 mg intravenously. The halflives for doses of 0.1-7 mg ranged from 13 to 18 minutes. At a dose of 50 mg, the half-life was 45 minutes. ...
Following oral administration of a radiolabeled 300- or 450-mg dose of pentosan polysulfate sodium solution, the mean half-life for plasma radioactivity was 27 or 20 hours, respectively.

Toxicity Summary
IDENTIFICATION AND USE: Elmiron (Pentosan polysulfate) is a white powder. Elmiron is a weak anticoagulant (1/15 the activity of heparin). it is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis. It is also used in veterinary medicine. HUMAN STUDIES: Elmiron, a highly sulfated, semisynthetic pentose polysaccharide with properties similar to heparin, is used for the treatment of interstitial cystitis. Overdose of Elmiron has not been reported. Based upon the pharmacodynamics of the drug, toxicity is likely to be reflected as anticoagulation, bleeding, thrombocytopenia, liver function abnormalities, and gastric distress. A case of severe thrombocytopenia and ischemic stroke following Elmiron treatment has been reported. The development of thrombocytopenia was reported in 25 patients receiving either heparin or Elmiron over a 7 month period. Based on platelet aggregation studies it was suggested that an immune allergic reaction to the anticoagulants occurred. ANIMAL STUDIES: Elmiron was orally administered once daily via gavage, 5 days per week, for up to 2 years. The dosages administered to mice were 56, 168 or 504 mg/kg. The dosages administered to rats were 14, 42, or 126 mg/kg for males, and 28, 84, or 252 mg/kg for females. Elmiron was carcinogenic to mice but not rats. Increased incidences of liver hemangiosarcoma, hepatocellular neoplasms (predominantly adenomas), and malignant lymphomas revealed carcinogenic activity of Elmiron in female mice. Reproduction studies have been performed in mice and rats with intravenous daily doses of 15 mg/kg, and in rabbits with 7.5 mg/kg. These studies did not reveal evidence of impaired fertility or harm to the fetus from Elmiron. Elmiron sodium was not clastogenic or mutagenic when tested in the mouse micronucleus test or the Ames test (Salmonella typhimurium).

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Interactions
The effect of pentosan polysulfate sodium on warfarin pharmacokinetics and pharmacodynamics was investigated in healthy subjects. Warfarin was titrated to an international normalized ratio between 1.4 and 1.8. Subjects continued their titrated dose of warfarin and received pentosan polysulfate sodium 100 mg or placebo every 8 hours for 7 days. The Cmax of R- and S-warfarin was approximately 840 to 890 ng/mL and 680 to 730 ng/mL, respectively, and was similar in the absence and presence of pentosan polysulfate sodium. The half-life for R- and S-warfarin was 52 to 56 hours and 36 to 40 hours, respectively. Prothrombin time, partial thromboplastin time, and the international normalized ratio for warfarin + placebo and warfarin + pentosan polysulfate sodium were comparable. The AUC(INR) indicated no treatment effect (P = .772); however, there was a period effect. Analysis of variance for the treatments by period indicated no treatment effect (P > .1). Adverse events were mild and included headache, epistaxis, and rash. Most adverse events were unrelated to treatment and were seen during warfarin titration. Pentosan polysulfate sodium did not affect warfarin pharmacokinetics or pharmacodynamics.
The risk of hemorrhage may be increased when pentosan polysulfate sodium is used concurrently with drugs that affect hemostasis (e.g., oral anticoagulants, heparin, nonsteroidal anti-inflammatory agents (NSAIAs), thrombolytic agents [e.g., alteplase]). Patients receiving such concomitant therapy should be monitored for hemorrhage.

[1]. Schuchman EH, et al. Pentosan polysulfate: a novel therapy for the mucopolysaccharidoses. PLoS One. 2013;8(1):e54459.
[2]. Baba M, et al. Pentosan polysulfate, a sulfated oligosaccharide, is a potent and selective anti-HIV agent in vitro. Antiviral Res. 1988 Sep;9(6):335-43.
[3]. Wu J, et al. Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice. Lab Invest. 2011 Oct;91(10):1459-71.

[(2R,3R,4S,5R)-2-Hydroxy-5-{[(2S,3R,4S,5R)-5-hydroxy-3,4-bis(sulfooxy)oxan-2-yl]oxy}-4-(sulfooxy)oxan-3-yl]oxidanesulfonic acid is a glycoside.
Pentosan polysulfate is a sulfated pentosyl polysaccharide with heparin-like properties.
Pentosan Polysulfate is a semisynthetic heparin-like glucosaminoglycan. Although its mechanism of action is unknown, pentosan polysulfate may act as a buffer to control cell permeability by preventing irritating solutes from reaching cells coated with it. Administered orally, excreted pentosan polysulfate adheres to the urinary bladder wall, preventing irritants from entering bladder cells and the development or progression of interstitial cystitis (IC), a complication of some chemotherapies. This agent also exhibits anticoagulant and fibrinolytic properties. (NCI04)
A sulfated pentosyl polysaccharide with heparin-like properties.
See also: Beta-D-Xylopyranose (has monomer); Pentosan Polysulfate Sodium (has salt form).

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Drug Indication
For the relief of bladder pain or discomfort associated with interstitial cystitis.
FDA Label

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Mechanism of Action
Pentosan polysulfate is a polymer of xylose hydrogen sulfate and contains two sulfate groups per carbohydrate monomer. It binds Fibroblast growth factors (FGFs) as well as other heparin-binding growth factors. It has been shown to interact also with the heparin-binding site of FGFR-1. It inhibits the growth of SW13 adrenocortical cells transfected with FGF-4 and tumorigenicity of MCF-7 breast carcinoma cells transfected with FGF-1 or FGF-4.

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Therapeutic Uses
Anticoagulants
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Elmiron is included in the database.
Elmiron (pentosan polysulfate sodium) is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis. /Included in US product labeling/
VET: Oral pentosan (human) has been used anecdotally for the adjunctive treatment of feline interstitial cystitis (feline idiopathic lower urinary tract disease - FLUTD), but studies have demonstrated that it is not effective for short-term, acute lower urinary tract disease.
For more Therapeutic Uses (Complete) data for Elmiron (13 total), please visit the HSDB record page.

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Drug Warnings
Elmiron is a weak anticoagulant (1/15 the activity of heparin). At a daily dose of 300 mg (n = 128), rectal hemorrhage was reported as an adverse event in 6.3% of patients. Bleeding complications of ecchymosis, epistaxis, and gum hemorrhage have been reported. Patients undergoing invasive procedures or having signs/symptoms of underlying coagulopathy or other increased risk of bleeding (due to other therapies such as coumarin anticoagulants, heparin, t-PA, streptokinase, high dose aspirin, or nonsteroidal anti-inflammatory drugs) should be evaluated for hemorrhage. Patients with diseases such as aneurysms, thrombocytopenia, hemophilia, gastrointestinal ulcerations, polyps, or diverticula should be carefully evaluated before starting Elmiron.
Elmiron has not been studied in patients with hepatic insufficiency. Because there is evidence of hepatic contribution to the elimination of Elmiron, hepatic impairment may have an impact on the pharmacokinetics of Elmiron. Caution should be exercised when using Elmiron in this patient population.
Alopecia, primarily alopecia areata (limited to a single area on the scalp), has been reported in patients receiving pentosan polysulfate sodium, and may occur within the first 4 weeks of initiation of therapy.
Safety and effectiveness in pediatric patients below the age of 16 years have not been established.
For more Drug Warnings (Complete) data for Elmiron (11 total), please visit the HSDB record page.

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Pharmacodynamics
Pentosan polysulfate sodium is a low molecular weight heparin-like compound. It has anticoagulant and fibrinolytic effects.

C10H18O21S4

601.922

37300-21-3

Pentosan Polysulfate Sodium (W/W 43%);140207-93-8

37720

White powder

2.26g/cm3

-5.6

356.07

6

21

10

35

1140

8

OS(O[C@H]1[C@H](O)CO[C@@H](O[C@@H]2CO[C@@H](O)[C@H](OS(=O)(O)=O)[C@H]2OS(=O)(O)=O)[C@@H]1OS(=O)(O)=O)(=O)=O

FCCNSUIJIOOXEZ-SJYYZXOBSA-N

InChI=1S/C10H18O21S4/c11-3-1-26-10(8(31-35(22,23)24)5(3)28-32(13,14)15)27-4-2-25-9(12)7(30-34(19,20)21)6(4)29-33(16,17)18/h3-12H,1-2H2,(H,13,14,15)(H,16,17,18)(H,19,20,21)(H,22,23,24)/t3-,4-,5+,6+,7-,8-,9-,10+/m1/s1

[(2R,3R,4S,5R)-2-hydroxy-5-[(2S,3R,4S,5R)-5-hydroxy-3,4-disulfooxyoxan-2-yl]oxy-3-sulfooxyoxan-4-yl] hydrogen sulfate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 1 mg/mL
H2O: 0.67 mg/mL

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。