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
◉ Overview of Use During Lactation
At normal oral doses, ketorolac concentrations in breast milk are low, but higher doses or nasal spray concentrations have not been measured in breast milk. In some hospital protocols, short-term (usually 24 hours) use of ketorolac injections after cesarean section has not been shown to be harmful to breastfed infants. However, due to the small volume of colostrum, the amount of ketorolac ingested by the infant from colostrum is very low. Some evidence suggests that intravenous ketorolac as part of a multimodal analgesia regimen after cesarean section reduces the rate of exclusive breastfeeding failure compared to patient-controlled intravenous morphine analgesia. Ketorolac has potent antiplatelet activity and may cause gastrointestinal bleeding. The manufacturer notes that ketorolac is contraindicated during lactation; therefore, alternative medications are recommended when milk production is high, especially in the first 24 to 72 hours postpartum, particularly when nursing newborns or premature infants.
The use of ketorolac eye drops by the mother is not expected to have any adverse effects on breastfed infants. To significantly reduce the amount of medication that enters breast milk after the eye drops are instilled, press the tear duct near the corner of the eye with your finger for at least 1 minute, then blot away any excess medication with absorbent tissue.
◉ Effects on breastfed infants
A randomized, double-blind study compared the efficacy of standard care to that of standard care plus multimodal analgesia (including a single intramuscular injection of 60 mg ketorolac during fascial suturing) to mothers who underwent cesarean section (n = 60) versus mothers who underwent standard care plus multimodal analgesia (including a single intramuscular injection of 60 mg ketorolac during fascial suturing) (n = 60). In the first month postpartum, there were no significant differences between the two groups in terms of neonatal growth abnormalities, feeding difficulties, or the incidence of neonatal sedation or respiratory depression.
◉ Impact on Lactation and Breast Milk
A randomized, double-blind study compared postpartum outcomes in mothers who underwent cesarean section (n = 60) receiving standard care versus those who received standard care plus multimodal analgesia (including a single intramuscular injection of 60 mg ketodrolic acid during fascial suturing) (n = 60). In the first month postpartum, breastfeeding rates were not significantly different between the two groups (78% and 79%, respectively).
In a study comparing standard care versus enhanced recovery after cesarean section, the enhanced recovery program included a fixed intravenous dose of 15 mg ketodrolic acid every 6 hours for 24 hours postpartum, while the standard program included on-demand intravenous injections of 15 mg ketodrolic acid. Patients using the enhanced recovery program (n = 58) had a higher rate of exclusive breastfeeding (67%) than those using the standard program (48%; n = 60).
A retrospective study evaluated 1349 women who underwent cesarean section and received ketodrolic acid within 15 minutes of the end of surgery. The results showed no difference in pain control during the first 6 hours post-surgery or the proportion of women breastfeeding at discharge. A prospective cohort study compared two pain control regimens after cesarean section: (1) patient-controlled analgesia (PCA) with morphine and ibuprofen administered at set times for the first 12 hours post-surgery, followed by continued ibuprofen administration at set times, with hydrocodone-acetaminophen added if necessary; (2) a multimodal analgesia regimen including: (3) oral acetaminophen 1000 mg every 8 hours post-surgery; (4) intravenous ketorolac 30 mg, followed by 15 mg every 8 hours for 24 hours; (5) oral ibuprofen 600 mg every 8 hours for the remainder of post-surgery, with opioids used only when necessary. Among women who planned to exclusively breastfeed at admission, the proportion of women using formula before discharge was lower in the multimodal analgesia group than in the conventional analgesia 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 the lead candidate drug for ROXRO and is currently undergoing a Phase III clinical trial for the treatment of acute pain, including postoperative pain. Ketoroxypropyl tromethamine is the tromethamine salt of ketoroxylic acid, a synthetic pyrrolizine carboxylic acid derivative with anti-inflammatory, analgesic, and antipyretic effects. Ketoroxypropyl tromethamine is a non-selective cyclooxygenase (COX) inhibitor that simultaneously inhibits COX-1 and COX-2 enzymes. This drug exerts its anti-inflammatory effect by inhibiting COX-2, which is undetectable in most tissues but highly expressed at sites of inflammation. Since COX-1 is expressed in almost all tissues, the drug's inhibition of COX-1 prevents the normal production of prostaglandins. Prostaglandins play a role in maintaining normal bodily functions, including protecting the gastrointestinal tract, regulating renal blood flow, and participating in platelet aggregation. Therefore, COX-1 inhibitors are often associated with adverse reactions such as gastrointestinal toxicity and nephrotoxicity. Ketoroxypropyl tromethamine is a pyrrolizine carboxylic acid derivative related to the structure of indomethacin. It is a nonsteroidal anti-inflammatory drug (NSAID) used for postoperative analgesia and to inhibit cyclooxygenase activity. See also: Ketodrolic acid (containing the active ingredient)... See more...

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Drug Indications
Studied for the treatment/relief of pain (acute or chronic).

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Mechanism of Action
ROX-888 is an intranasal formulation of the widely used injectable analgesic ketordrolic acid. It effectively relieves moderate to severe pain caused by acute illnesses without the serious 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。