在囊性纤维化 (CF) 折叠上皮 IB3-1 和 CuFi-1 细胞中，miglustat（200 μM；2、4 和 24 小时）可恢复 F508del-CFTR（囊性纤维化跨膜电导调节剂）功能。 Miglustat 可减轻铜绿假单胞菌在 CF 和非 CF 细胞中引起的严重反应 [1]。

Miglustat（0.2 mg/kg；屏障；一次）对过度兴奋做出反应，修复突触可塑性缺陷，并重新激活 ERK [2]。

Animal/Disease Models: NPC1−/− mice[1]
Doses: 0.2 mg/kg
Route of Administration: po (po (oral gavage))
Experimental Results: Able to rescue synaptic plasticity defects, restore ERK activation and counteract hyperexcitability.

Absorption, Distribution and Excretion
Mean oral bioavailability is 97%.

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Metabolism / Metabolites
There is no evidence that miglustat is metabolized in humans.

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Biological Half-Life
The effective half-life of miglustat is approximately 6 to 7 hours.

Hepatotoxicity
In placebo controlled trials, liver test abnormalities were no more common with miglustat than with placebo treatment, and what abnormalities occurred were mild and resolved spontaneously usually without need for dose interruption. During these premarketing clinical trials and since its more widespread clinical availability, no instances of acute liver injury with jaundice have been reported attributable to miglustat. However, the total clinical experience with its use has been limited.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No published experience exists with miglustat during breastfeeding. Because of the lack of information and its side effect profile, most sources consider breastfeeding to be contraindicated during maternal miglustat therapy.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
◈ What is miglustat?
Miglustat is a medication that has been used for treatment of mild to moderate Gaucher disease type 1. It has also been used to treat Niemann-Pick disease type C. Miglustat is sold under the brand name Zavesca®.People with Gaucher disease have low levels of an enzyme called glucocerebrosidase (gloo-co-se-ruh-BRO-si-dace). This enzyme helps break down fatty substances in the body. When this enzyme is missing or not working, fatty substances build up and can cause organ damage. Miglustat works in the body to limit the amount of the fatty substances being made. For more information, see the MotherToBaby fact sheet on Gaucher disease at https://mothertobaby.org/fact-sheets/gaucher-disease-pregnancy/.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I take miglustat. Can it make it harder for me to get pregnant?
Studies have not been done in humans to see if miglustat could make it harder to get pregnant.
◈ Does taking miglustat increase the chance of miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. Studies have not been done in humans to see if miglustat could increase the chance for miscarriage. Studies in animals found a greater chance of pregnancy loss at doses around twice as much as would be used in human therapy.
◈ Does taking miglustat increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Studies have not been done in humans to see if miglustat increases the chance for birth defects. Animal studies done by the manufacturer did not find an increased chance of births defects.
◈ Does taking miglustat in pregnancy increase the chance of other pregnancy-related problems?
Studies have not been done in humans to see if miglustat increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth). Animal studies done by the manufacturer reported a higher chance of low birth weight.
◈ Does taking miglustat in pregnancy affect future behavior or learning for the child?
Studies have not been done in humans to see if miglustat causes cause long-term problems in behavior or learning.
◈ Breastfeeding while taking miglustat:
There are no studies looking at miglustat use while breastfeeding. The product label for miglustat states that because there is no data available, use during breastfeeding is not recommended. But, the benefit of using miglustat may outweigh possible risks. Your healthcare providers can talk with you about using miglustat and what treatment is best for you. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes miglustat, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
In humans, one report did not find that miglustat use in 5 males affected the production of sperm or their fertility. Animal studies in rats found that miglustat exposure lowered sperm production, which lowered fertility. However, this was not found in all animal studies; and some animal strains are more sensitive to this exposure. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at  https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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Protein Binding
Miglustat does not bind to plasma proteins.

[1]. Anti-inflammatory effect of miglustat in bronchial epithelial cells. J Cyst Fibros. 2008 Nov;7(6):555-65.

[2]. Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease. Neural Plast. 2016:2016:3830424.

Pharmacodynamics
Miglustat, an N-alkylated imino sugar, is a synthetic analogue of D-glucose. Miglustat is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for catalyzing the formation of glucosylceramide (glucocerebroside). Glucosylceramide is a substrate for the endogenous glucocerebrosidase, an enzyme that is deficient in Gaucher's disease. The accumulation of glucosylceramide due to the absence of glucocerebrosidase results in the storage of this material in the lysosomes of tissue macrophages, leading to widespread pathology due to infiltration of lipid-engorged macrophages in the viscera, lymph nodes, and bone marrow. This results in secondary hematologic consequences including sever anemia and thrombocytopenia, in addition to the characteristic progressive hepatosplenomegaly, as well as skeletal complications including osteonecrosis and osteopenia with secondary pathological fractures.

C10H21NO4

219.27804

219.147

72599-27-0

Miglustat hydrochloride;210110-90-0

51634

White to off-white solid powder

1.2±0.1 g/cm3

394.7±42.0 °C at 760 mmHg

169-172 °C
169 - 172 °C

215.4±26.5 °C

0.0±2.1 mmHg at 25°C

1.546

0.46

84.16

4

5

4

15

190

4

CCCCN1C[C@@H]([C@H]([C@@H]([C@H]1CO)O)O)O

UQRORFVVSGFNRO-UTINFBMNSA-N

InChI=1S/C10H21NO4/c1-2-3-4-11-5-8(13)10(15)9(14)7(11)6-12/h7-10,12-15H,2-6H2,1H3/t7-,8+,9-,10-/m1/s1

(2R,3R,4R,5S)-1-Butyl-2-(hydroxymethyl)piperidine-3,4,5-triol

OGT918 OGT 918 OGT-918 N-butyldeoxynojirimycin NB-DNJ N-Butylmoranoline Zavesca.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

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

H2O : ~250 mg/mL (~1140.09 mM)

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。