◉ Summary of Use during Lactation:Marine oils, such as fish oil or algal oil, are a rich source of omega-3 fatty acids, especially the essential fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Algal oil is high in DHA and low in EPA, whereas fish oil has more EPA than DHA. DHA and EPA are normal components of breastmilk where concentrations reflect maternal intake. The DHA level in breastmilk is typically between 0.2% and 0.3% in Western countries. This is usually sufficient to meet the DHA requirements of term breastfed infants, but not the higher requirements of pre-term infants, where additional maternal supplementation is needed. Maternal supplementation increases breastmilk levels of DHA and EPA, although it appears that milk concentrations depend more on long-term intake than short-term (past 3-days) intake. Higher milk levels result in higher infant plasma and erythrocyte levels of omega-3 fatty acid-derived phospholipid; one study found that breastmilk DHA was a better predictor of infant erythrocyte DHA than direct supplementation of the infants with fish oil. Current dietary recommendations for nursing mothers is 250 to 375 mg daily of DHA plus EPA. Lactating women require a daily dosage of about 1000 mg DHA plus EPA to reach a milk DHA plus EPA of 1 gram/dL at 4 weeks postpartum.
Supplementation with omega-3 fatty acids has been studied for reduction of postpartum depression in nursing mothers and for improving various infant outcomes. A meta-analysis of 35 randomized, controlled trials found that women with a diagnosis of severe depression obtained benefit from omega-3 fatty acids, but those with mild depression did not.
Several meta-analyses have been performed on fish oil supplementation during breastfeeding. They found no beneficial effect of omega-3-fatty acid supplementation during breastfeeding on infant problem-solving ability, intelligence, socioemotional, psychomotor or motor development, visual acuity, growth or language development, academic performance, risks of attention deficit disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, anxiety, or depression. The most recent and comprehensive meta-analysis found that supplementation improved measures of cognitive development in the infant or child by 6 to 11%. Two meta-analyses found that maternal supplementation with omega-3-polyunsaturated fatty acids during lactation had little or no beneficial effect on childhood allergic diseases. A more recent large study found that DHA 1.2 grams daily given to nursing mothers did not improve their infants’ neurodevelopmental outcomes at 18 to 22 months of age in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks’ gestational age.
Weak evidence for improved vision and attention was found in one study. Long-term follow-up of a small group of children whose mothers received fish oil supplements during lactation found that boys had a delayed puberty, shorter average height, and higher systolic blood pressure at age 13 years. Other studies found that maternal fish oil supplementation during pregnancy and lactation reduced oxidative stress in their breastfed infants. Supplementation of nursing mothers with fish oil of about 800 mg of DHA plus EPA for 6 months altered the infant intestinal microbiome in a way that might decrease resistance to colonization with pathogens. However, no increase in infant illnesses were seen. Infants breastfed by overweight or obese mothers who took 3 grams of fish oil daily had greater ponderal index and reduced insulin resistance compared to placebo at 3 months of age.
Fish oil up to 3 grams daily is “generally recognized as safe” (GRAS) as a food by the U.S. Food and Drug Administration. The most common complaint is burping a fishy taste after ingestion. However, breast milk odor is not changed by maternal fish oil consumption. Rarely, allergic reactions are reported with nut oil-derived omega-3 fatty acids in patients allergic to nuts.
Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products. More detailed information about dietary supplements is available elsewhere on the LactMed Web site.
◉ Effects in Breastfed Infants:Ninety-five pregnant women at risk of having an allergic infant were randomized to daily supplements of 2.7 grams of omega-3 fatty acids (EPA 1.6 grams and DHA 1.1 grams) or a placebo from week 25 of pregnancy until 3 months of lactation. Infants of supplemented mothers had fewer allergies than unsupplemented infants, but it is unclear is the results were caused by transfer during pregnancy or during lactation.
A small sample of children whose mothers were randomized to receive either fish oil or olive oil during the first 4 months of lactation were examined at 13 years of age. Boys, but not girls, whose mothers received fish oil supplements trended towards short heights, apparently because of a delay in puberty. Boys also had a statistically significantly higher systolic blood pressure by an average of 3.9 mm Hg than girls.
One study found that supplementation of mothers with fish oil during pregnancy and postpartum lactation decreased plasma hydroperoxides especially in newborn at delivery and at 2.5 months of age and increased superoxide dismutase and catalase in breastfed infants newborns at 2.5 months of age. All of these changes indicate a decrease in oxidative stress in the infants.
Fifty-two breastfeeding mothers provided milk samples at 3 months postpartum for fatty acid analysis and completed the Infant Behavior Questionnaire. Infants whose mothers’ milk was richer in n-3 PUFAs had lower scores on the negative affectivity domain of the IBQ-R, a component of temperament associated with a risk for internalizing disorders later in life. These associations remained statistically significant after considering covariates, including maternal age, marital status, and infant birth weight. The n-6 PUFAs, n-6/n-3 ratio, and total fat of milk were not associated with infant temperament.
Milk samples from the mothers of 120 breast-fed infants were collected at 42 days and 8 months postpartum in Beijing, China. Breast milk EPA levels at both 42 days and 8 months postpartum were negatively associated with infant distractibility when EPA levels were low, suggesting a beneficial effect of higher EPA in breast milk (i.e., improving infant’s attention) when its levels are below a certain threshold.
A study of breastfed preterm infants (<29 weeks gestational age) whose mothers were randomized to receive 1.2 grams daily of DHA as algal oil or placebo found that there was no difference in the rate of bronchopulmonary dysplasia-free survival at 36 weeks between the groups. However, the study was stopped early because of concern for harm.
Mother-infant dyads (n = 27) were enrolled at birth and mothers were assigned to receive either 200 mg or 1000 mg daily of DHA (Expecta). All infants were born at less than 28 weeks gestation. Milk and plasma samples were analyzed for fatty acids and inflammatory markers. Decreases in inflammatory markers (TNF alpha, IL-12p70 and sRAGE) were observed in infant plasma in the high-dose group and correlated with infant red blood cell DHA levels. A follow-up study on 14 of the women who provided a milk sample at 4 weeks postpartum found differential expression of 409 genes in milk. Five main groups of biological processes were upregulated, including those associated with improved immune regulation and management of oxidative stress. Three main groups of biological processes were downregulated, including one associated with immune dysregulation.
A study randomized study of lactating mothers who delivered before 29 weeks’ gestation were given either 1.2 grams of DHA daily (n = 199 mothers, 234 infants) to achieve >1% of DHA in breast milk or placebo (N = 200 mothers, 223 infants) starting within 72 hours of delivery until 36 weeks postmenstrual age. Infants were assessed at 18 to 22 months postpartum with the Bayley-III cognitive, language, and motor composite scores. DHA did not improve infants neurodevelopmental outcomes at 18 to 22 months of age in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks’ gestational age.
A double-blind randomized controlled trial compared 6 grams of fish oil daily (3.55 grams daily of n-3 PUFAs) to olive oil (control) from mid-pregnancy until 3 months postpartum in women who were overweight or obese (BMI 25 kg/sq m. or greater). Most of the mothers exclusively breastfed their infants. Ninety-eight infants of the 128 mothers in the study had body fat measurements at 2 weeks and 3 months postpartum. There were no treatment effects on infant outcomes at 2 weeks, but infants in the fish oil arm had a higher BMI z-score and ponderal index at age 3 months of age. Fish oil supplementation lowered infant triglycerides by 21% at 3 months of age, but it did not affect infant insulin resistance.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
Icosapent ethyl is de-esterfied, converted into active EPA, and then absorbed in the small intestine. It reaches peak plasma concentration in 5 hours post-oral administration. Very little (<1%) is left circulating in the plasma as EPA incorporates into phospholipids, TG's, and cholesteryl esters.
来源:DrugBank
吸收、分配和排泄
消除途径
乙基二十碳五烯酸不会通过肾脏排泄。
Icosapent ethyl is not renally excreted
来源:DrugBank
吸收、分配和排泄
分布容积
活性的EPA稳态分布体积为88升。
Steady state volume of distribution of active EPA is 88 L
通过固定化的南极假丝酵母的非区域特异性酵母脂肪酶高效合成纯二十碳五烯酸1或二十二碳六烯酸2的均质甘油三酸酯描述。使用了两种方法：三丁酸甘油酯的酯交换和分别以化学计量的99％EPA或DHA的乙基酯和游离脂肪酸的甘油直接酯化。两种方法均在真空下于65°C且无任何溶剂的条件下进行。将挥发性副产物冷凝到冷却的阱中，从而使平衡朝着完成方向移动。在所有情况下，都可以在不到72小时的时间内完成完全掺入，但是发现直接酯化比酯交换要快得多，这两个过程都涉及EPA和DHA。高场11 H NMR光谱分析提供了在直接酯化反应过程中对中间甘油酯的详细研究。以优异的产率提供的所得粗产物的纯度非常高。
The invention relates to compounds of formula (I), useful for treating disorders mediated by the 5-hydroxytryptamine (serotonin) receptor IB (5-HT1B), e.g. vascular disorders, cancer and CNS disorders. The invention also provides methods of treating such disorders, and compounds and compositions etc. for their treatment.
[EN] LIPID COMPOUNDS AND COMPOSITIONS AND THEIR OPTHALMIC USE<br/>[FR] COMPOSÉS LIPIDIQUES ET COMPOSITIONS ASSOCIÉES ET LEUR UTILISATION OPHTALMIQUE
申请人：BIOZEP AS
公开号：WO2017093732A1
公开（公告）日：2017-06-08
The invention relates to lipid compounds of formula (I) and their pharmaceutically acceptable salts for the prevention and/or treatment of ophthalmic disorders such as retinal degenerative disorders and ocular inflammatory diseases: (I) (wherein R1 is either a C9 to C22 alkyl group, or a C9 to C22 alkenyl group having from 1 to 6 double bonds; R2 is selected from the group consisting of a halogen atom, a hydroxy group, an alkyl group, an alkoxy group, an alkylthio group, a carboxy group, an acyl group, an amino group, and an alkylamino group; R3 is a hydrogen atom, or a group R2; R4 is a carboxylic acid or a derivative thereof; and X is methylene (-CH2-), or an oxygen or sulfur atom).
[EN] 5-HT RECEPTOR MODULATORS<br/>[FR] MODULATEURS DU RÉCEPTEUR DE LA 5-HT
申请人：CAMBRIDGE ENTPR LTD
公开号：WO2011098776A1
公开（公告）日：2011-08-18
The invention relates to compounds of formula (I), useful for treating disorders mediated by the 5-hydroxytryptamine (serotonin) receptor IB (5-HT1B), e.g. vascular disorders, cancer and CNS disorders. The invention also provides methods of treating such disorders, and compounds and compositions etc. for their treatment.
Chemoenzymatic synthesis of a focused library of enantiopure structured 1-O-alkyl-2,3-diacyl-sn-glycerol type ether lipids
作者：Carlos D. Magnusson、Anna V. Gudmundsdottir、Gudmundur G. Haraldsson
DOI：10.1016/j.tet.2011.01.032
日期：2011.3
A highly efficient two-step chemoenzymatic synthesis of enantiopure structured ether lipids of the 1-O-alkyl-2,3-diacyl-sn-glycerol type has been developed. Chimyl, batyl and selachyl alcohols possessing pure saturated fatty acid (SFA) attached to the sn-3 position and pure EPA and DHA attached to the sn-2 position were obtained under full regiocontrol. This was offered by mild conditions and a highly
已经开发了1- O-烷基-2，3-二酰基-sn-甘油类型的对映纯结构化醚脂质的高效两步化学酶法合成。在完全区域控制下，获得了具有附接到sn -3位置的纯饱和脂肪酸（SFA）和附接到sn -2位置的纯EPA和DHA的Chimyl，batyl和selachyl醇。这是由温和条件和在室温下运行的高效脂肪酶提供的。高分辨率11 H NMR光谱法用于监测反应的进程，并通过跟踪参与这些反应的所有预期加合物来评估所涉及反应的完全区域控制。这扩展为针对C 2 -C 16的所有偶数SFA以及八个相应的EPA和DHA结构化的二酰基甘油醚（DAGE）产品（用于chimyl，batyl和selachyl醇）的八个单酰基中间加合物的重点文库的制备。总共72种化合物。
[EN] AMINOPYRROLIDINONE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS D'AMINOPYRROLIDINONE ET UTILISATIONS DE CEUX-CI
申请人：LINK MEDICINE CORP
公开号：WO2010141932A1
公开（公告）日：2010-12-09
The present invention provides compounds of formula (I):or a pharmaceutically acceptable salt thereof, wherein each of Ring A, Ring B, T, R2, R2', and RA is as defined and described herein and methods for treating subjects or patients with a disease, disorder, or condition.
