酮咯酸是一种非甾体类抗炎药。 COX-1 和 COX-2 的 IC50 值分别表明该化合物是一种非选择性 COX 抑制剂 [1]。

LPS 内毒素引起的前房 FITC-葡聚糖的升高和房水中 PGE2 含量的升高几乎完全被酮咯酸氨丁三醇 (0.4%) 抑制 [1]。静脉注射酮咯酸（30 mg/kg）可迅速逆转大鼠的痛觉过敏。此外，酮咯酸可以降低大鼠体内 PGE2 水平，并减少爪子 PG 合成和角叉菜胶引起的痛觉过敏 [1]。大鼠牙槽窝产生的骨小梁体积分数不受口服酮咯酸（4 mg/kg/天）的影响[2]。酮咯酸（60 μg/10 μL）可减少大鼠缺血性细胞死亡，包括细胞质嗜酸性粒细胞增多、细胞紊乱和核固缩。此外，酮咯酸可以增强后肢运动功能，显着减少神经元死亡，并且具有与对照组相当的长期生存率[3]。

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Milk levels of ketorolac are low with the usual oral dosage, but milk levels have not been measured after higher injectable dosages or with the nasal spray. Ketorolac injection is used for a short time (typically 24 hours) after cesarean section in some hospital protocols with no evidence of harm to breastfed infants. However, the ketorolac dose an infant receives in colostrum is very low because of the small volume of colostrum produced. Some evidence suggests that IV ketorolac as part of a multimodal post-cesarean section analgesia reduces percentage of mothers who fail exclusive breastfeeding compared to patient-controlled IV morphine-based analgesia. Ketorolac has strong antiplatelet activity and can cause gastrointestinal bleeding. The manufacturer indicates that ketorolac is contraindicated during breastfeeding, so an alternate drug is preferred after the first 24 to 72 hours when larger volumes of milk are produced, especially while nursing a newborn or preterm infant.
Maternal use of ketorolac eye drops would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.
◉ Effects in Breastfed Infants
A randomized, double-blind study compared standard care of mothers receiving a cesarean section delivery (n = 60) to those receiving standard care plus multimodal pain management that included a single dose of 60 mg of intramuscular ketorolac given at the time of fascial closure (n = 60). No significant differences in abnormal neonatal growth, difficulty feeding, neonatal sedation, or respiratory depression rates between the two groups were seen during the first month postpartum.
◉ Effects on Lactation and Breastmilk
A randomized, double-blind study compared standard care of mothers receiving a cesarean section delivery (n = 60) to those receiving standard care plus multimodal pain management that included a single dose of 60 mg of intramuscular ketorolac given at the time of fascial closure (n = 60). No significant differences in breastfeeding rates (78% and 79%, respectively) were seen during the first month postpartum.
In a study comparing standard of care to enhanced recovery after cesarean section deliveries, a fixed dose of ketorolac 15 mg every 6 hours intravenously for 24 hours postpartum was part of the enhanced recovery protocol whereas as needed ketorolac 15 mg intravenously was part of the standard protocol. Patients in the enhanced recovery protocol (n = 58) had a greater frequency of exclusive breastfeeding (67%) than those in the standard protocol (48%; n = 60).
A retrospective study evaluated 1349 women who had undergone a cesarean section and were given ketorolac within 15 minutes of the end of surgery. The results indicated that there was no difference in pain control in the first 6 hours after surgery nor in the percentage of women who were breastfeeding at discharge.
A prospective cohort study of postcesarean pain control compared (1) morphine PCA and scheduled ibuprofen for the first 12 hours followed by continued scheduled ibuprofen with hydrocodone-acetaminophen as needed to a multimodal pain management regimen consisting of (2) acetaminophen 1000 mg orally every 8 hours, ketorolac 30 mg IV once initially, then 15 mg IV every 8 hours for 24 hours, then ibuprofen 600 mg orally every 8 hours for the remainder of the postoperative course with opioids given only as needed. Of women who planned to exclusively breastfeed on admission, fewer women used formula prior to discharge in the multimodal group compared to the traditional group (9% vs. 12%).

[1]. Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin. 2006 Jun;22(6):1133-40.

[2]. Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats. J Appl Oral Sci. 2010 Dec;18(6):630-4.

[3]. Intrathecal ketorolac pretreatment reduced spinal cord ischemic injury in rats. Anesth Analg. 2005 Apr;100(4):1134-9.

ROX-888 is ROXRO's lead compound which is currently in Phase 3 trials for the treatment of acute pain, including post-operative pain.
Ketorolac Tromethamine is the tromethamine salt of ketorolac, a synthetic pyrrolizine carboxylic acid derivative with anti-inflammatory, analgesic and antipyretic properties. Ketorolac tromethamine, a non-selective inhibitor of the cyclooxygenases (COX), inhibits both COX-1 and COX-2 enzymes. This agent exerts its anti-inflammatory effect by preventing conversion of arachidonic acid to prostaglandins at inflammation site mediated through inhibition of COX-2, which is undetectable in most tissues but is up-regulated at the inflammation sites. Since COX-1 is expressed virtually in all tissues, inhibition of COX-1 enzyme by this agent prevents normal state production of prostaglandins, which plays housekeeping roles in the protection of the gastrointestinal tract, regulating renal blood flow, and functioning in platelet aggregation. As a result, inhibition of COX-1 is usually associated with adverse effects such as gastrointestinal toxicity and nephrotoxicity.
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity.
See also: Ketorolac (has active moiety) ... View More ...

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Drug Indication
Investigated for use/treatment in pain (acute or chronic).

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Mechanism of Action
ROX-888 is a intranasal formulation of the broadly used injectible analgesic, ketorolac. It has ability to provide effective analgesia in acute medical conditions resulting in moderate-severe pain, without the disabling side effects of opioid analgesics

C26H28FN3O9

545.52

376.163

74103-07-4

Ketorolac;74103-06-3;(S)-Ketorolac;66635-92-5;(R)-Ketorolac;66635-93-6

84003

White to off-white solid powder

493.2ºC at 760 mmHg

160-161ºC

252.1ºC

0.652

146.01

5

7

6

27

430

0

2-amino-2-(hydroxymethyl)propane-1,3-diol 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylate

BWHLPLXXIDYSNW-UHFFFAOYSA-N

2-amino-2-(hydroxymethyl)propane-1,3-diol;5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid

Acular Godek Sprix Syntex Toradol Ketorolac tromethamine

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/受潮和光照。

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

H2O : ~100 mg/mL (~265.67 mM)
DMSO : ≥ 30 mg/mL (~79.70 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (5.53 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (5.53 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (5.53 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 100 mg/mL (265.67 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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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。