Glucocorticoid receptor

本研究合成了一系列新型聚甲基丙烯酸2-羟乙酯（PHEMA）/聚N，N'-二甲基丙烯酰胺（PDMAM）互穿聚合物网络（IPNs），并研究了其作为地塞米松磷酸钠（DXP）皮肤应用的潜在药物递送系统。IPN组合物允许控制其溶胀能力，因为与PHEMA单网络相比，高度亲水性PDMAM的掺入使IPN溶胀比增加了一倍以上，即从~0.5增加到~1.1。IPNs溶胀率的增加导致包封率提高至约30%，DXP的载药量提高至4.5%。X射线衍射（XRD）和差示扫描量热法（DSC）显示药物DXP和聚合物（IPN）基质之间形成固体分散体。能量色散X射线（EDX）光谱显示DXP在IPN结构内均匀分布。DXP的释放遵循Fickian扩散，24小时内释放约70%的DXP。这项研究证明了新开发的IPN在DXP皮肤递送方面的潜力[1]。

隐形眼镜（CL）已被建议作为药物递送平台，能够增加药物在角膜上的停留时间，从而提高其生物利用度。然而，当靶向眼睛的后段时，CL释放的药物仍然会遇到眼部组织的屏障效应，这大大降低了给药的疗效。这项工作旨在开发能够同时递送抗炎药物（地塞米松磷酸钠）和细胞穿透肽（渗透素）的CL，后者作为药物载体穿过组织。甲基丙烯酸羟乙酯（HEMA）基水凝胶用丙烯酸（AAc）和/或氨基丙基甲基丙烯酰胺（APMA）官能化，作为CL材料，对药物和肽的亲和力增加。APMA功能化水凝胶持续双重释放8小时，这与每日CL的佩戴时间相容。水凝胶具有合适的透光性、溶胀性和体外生物相容性。该药物的抗炎活性不会因肽的存在或灭菌而受到损害。在兔子体内评估了CL佩戴6小时后药物的眼部分布，结果表明，当药物与渗透素共递送时，角膜和房水中的药物量显著增加[2]。

Background: Efficacy of erythrocyte-mediated delivery of dexamethasone 21-phosphate in patients with steroid-dependent ulcerative colitis.[3]
Methods: Thirty-seven patients with steroid-dependent ulcerative colitis were randomized to infusions of dexamethasone 21-phosphate encapsulated into autologous erythrocytes (n = 19) or to sham infusions (n = 18). Each infusion was given monthly for 6 months. The primary endpoint was the proportion of patients able to discontinue oral corticosteroids during treatment while maintaining clinical remission or stable disease. Secondary endpoint was the proportion of patients with disappearance of steroid-related adverse events.[3]
Results: At each infusion, a mean of 9.8 ± 4.6 mg dexamethasone 21-phosphate was administered at each infusion, which allowed steady-state plasma levels of 8 ng/mL for the following 28 days. Thirteen patients in the dexamethasone 21-phosphate group and 4 sham-treated patients attained the primary outcome of the study, i.e., maintaining a stable condition despite oral steroids withdrawal (P = 0.008). In the remaining patients (6 and 15 in the 2 experimental groups, respectively), the treatment was prematurely withdrawn because of clinical deterioration while tapering oral steroids. At endoscopy, mucosal healing was ascertained in 4 patients and 1 patient of the 2 experimental groups, respectively (P = 0.339). At inclusion, 14 and 13 patients in the 2 experimental groups complained of steroid-related adverse events; at end of the treatment, events were still present in 5 and 13 patients, respectively (P = 0.008).[3]
Conclusions: In patients with steroid-dependent ulcerative colitis, 6-month therapy with low dose of dexamethasone 21-phosphate allowed the withdrawal of oral steroids and the reversal of steroid-related adverse events in most patients while maintaining clinical remission (ClinicalTrials.gov number, NCT01171807).

[1]. Interpenetrating Polymer Networks of Poly(2-hydroxyethyl methacrylate) and Poly(N, N-dimethylacrylamide) as Potential Systems for Dermal Delivery of Dexamethasone Phosphate. Pharmaceutics . 2023 Sep 15;15(9):2328.
[2]. Dexamethasone phosphate and penetratin co-eluting contact lenses: a strategy to enhance ocular drug permeability. Int J Pharm . 2024 Jan 25:650:123685.
[3]. Erythrocytes-mediated delivery of dexamethasone 21-phosphate in steroid-dependent ulcerative colitis: a randomized, double-blind Sham-controlled study. Inflamm Bowel Dis. 2013 Aug;19(9):1872-9.

Dexamethasone phosphate is a steroid phosphate that is the 21-O-phospho derivative of dexamethasone. It has a role as a glucocorticoid receptor agonist. It is a steroid phosphate, an 11beta-hydroxy steroid, a 17-hydroxy steroid, a 3-oxo-Delta(4) steroid, a fluorinated steroid and a tertiary alpha-hydroxy ketone. It is functionally related to a dexamethasone. It is a conjugate acid of a dexamethasone phosphate(2-).
See also: Dexamethasone sodium phosphate; neomycin sulfate (annotation moved to).

C22H30FO8P

472.4462

472.166

C, 55.93; H, 6.40; F, 4.02; O, 27.09; P, 6.56

312-93-6

Dexamethasone;50-02-2;Dexamethasone acetate;1177-87-3;Dexamethasone phosphate disodium;2392-39-4;Dexamethasone phosphate-d4

9400

Typically exists as solid at room temperature

1.45g/cm3

669.6ºC at 760mmHg

154-157°C (lit.)

358.7ºC

1.594

2.012

151.17

4

9

4

32

973

8

C[C@@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@]3([C@H](C[C@]2(C)[C@]1(C(=O)COP(=O)(O)O)O)O)F

VQODGRNSFPNSQE-CXSFZGCWSA-N

InChI=1S/C22H30FO8P/c1-12-8-16-15-5-4-13-9-14(24)6-7-19(13,2)21(15,23)17(25)10-20(16,3)22(12,27)18(26)11-31-32(28,29)30/h6-7,9,12,15-17,25,27H,4-5,8,10-11H2,1-3H3,(H2,28,29,30)/t12-,15+,16+,17+,19+,20+,21+,22+/m1/s1

[2-[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] dihydrogen phosphate

Dexamethasone 21-phosphate; EGP437 Dexamethasone phosphate; EGP-437; EGP 437; Hexadrol phosphate; Wymesone; Betnelan phosphate; Neodecadron; Oradexon phosphate; Dexamethasone 21-phosphate; 312-93-6; Betnelan phosphate; Neodecadron; Hexadrol phosphate; Dexamethasone-21-dihydrogen-phosphate; Dexamethasone 21-orthophosphate;

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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。