Poor aqueous solubility and the unpleasant taste of aripiprazole (APZ) have been recurring problems, owing to its low bioavailability and low patient tolerance, respectively. Herein, we prepared a nanohybrid system that was based on a bentonite clay material, montmorillonite (MMT), which could both mask the taste and enhance the solubility of APZ (i.e., APZ-MMT). To further improve the efficacy of this taste masking and drug solubility, APZ-MMT was also coated with a cationic polymer, polyvinylacetal diethylamino acetate (AEA). In vitro dissolution tests at neutral pH showed that the amount of drug that was released from the AEA-coated APZ-MMT was greatly suppressed (<1%) for the first 3 min, thus suggesting that AEA-coated APZ-MMT has strong potential for the taste masking of APZ. Notably, in simulated gastric juice at pH 1.2, the total percentage of APZ that was released within the first 2 hr increased up to 95% for AEA-coated APZ-MMT. Furthermore, this in vitro release profile was also similar to that of Abilify(c), a commercially available medication. In vivo experiments by using Sprague-Dawley rats were also performed to compare the pharmacokinetics of AEA-coated APZ-MMT and Abilify(c). AEA-coated APZ-MMT exhibited about 20% higher systemic exposure of APZ and its metabolite, dehydro-APZ, compared with Abilify(c). Therefore, a new MMT-based nanovehicle, which is coated with a cationic polymer, can act as a promising delivery system for both taste masking and for enhancing the bioavailability of APZ.
The present study was designed to investigate the effects of montmorillonite (MMT) on dietary Cd-induced oxidative damage in liver and kidney of carp (Carassius auratus). One hundred eighty carp were randomly divided into four groups and fed with a basal diet, a basal diet supplemented with 0.5% MMT, Cd-comtaminated basal diet (120 mg Cd/kg dry weight) and Cd-contaminated basal diet supplemented with 0.5% MMT, respectively. After 60 days, fish were sacrificed to measure malondialdehyde (MDA) content and antioxidative indices in liver and kidney. The results showed that the exposure of carp to dietary Cd caused decreases in glutathione peroxidase activity, catalase activity, superoxide dismutase activity, glutathione content and total antioxidant capacity level, while MMT supplemented in diet compensated Cd-induced decreases in above antioxidant indices to some extent in liver and kidney. As compared with the control group, increases in MDA content were observed in both measured tissues of carp exposed to dietary Cd, while MDA content decreased in carp exposed to Cd-contaminated basal diet supplemented with MMT in comparison with the Cd-contaminated group. It was suggested that MMT, when co-administered with Cd in diet, could alleviate dietary Cd-induced oxidative damage in liver and kidney of carp.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Combinations of Pyrazole Kinase Inhibitors and Further Antitumor Agents
申请人：Curry Jayne Elizabeth
公开号：US20080161355A1
公开（公告）日：2008-07-03
The invention provides a combination of a compound having the formula (0) and two or more further anti-cancer agents: or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R
1
-A-NR
4
— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NR
9
(C═O) or 0(C═O) wherein R
9
is hydrogen or C
1-4
hydrocarbyl optionally substituted by hydroxy or C
1-4
alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R
1
is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C
1-8
hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C
1-4
hydrocarbyloxy, amino, mono- or di-C
1-4
hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO
2
; R
2
is hydrogen; halogen; C
1-4
alkoxy (e.g. methoxy); or a C
1-4
hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C
1-4
alkoxy (e.g. methoxy); R
3
is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R
4
is hydrogen or a C
1-4
hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C
1-4
alkoxy (e.g. methoxy).
The invention provides a combination of a cytotoxic compound or signalling inhibitor and a compound having the formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R
1
-A-NR
4
- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO
2
, C═O, NR
g
(C═O) or 0(C═O) wherein R
g
is hydrogen or C
1-4
hydrocarbyl optionally substituted by hydroxy or C
1-4
alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R
1
is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C
1-8
hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C
1-4
hydrocarbyloxy, amino, mono- or di-C
1-4
hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO
2
; R
2
is hydrogen; halogen; C
1-4
alkoxy (e.g. methoxy); or a C
1-4
hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C
1-4
alkoxy (e.g. methoxy); R
3
is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R
4
is hydrogen or a C
1-4
hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C
1-4
alkoxy (e.g. methoxy).
1,8 Naphthyridine derivatives and their use to treat diabetes and related disorders
申请人：Bayer Pharmaceuticals Corporation
公开号：US20040209866A1
公开（公告）日：2004-10-21
The invention relates generally to naphthyridine derivatives of the formula
1
wherein one of U, X, Y and Z is nitrogen and the others are C—R, where R is hydrogen or a substituent. More specifically, the invention relates to 1,8-naphthyridine derivatives and pharmaceutical compositions containing such derivatives. Methods of the invention comprise administration of a naphthyridine derivative of the invention for the treatment of diabetes and related disorders.
Nitrogen containing heterocyclic compounds and medicines containing the same
申请人：Ozaki Fumihiro
公开号：US20050245527A1
公开（公告）日：2005-11-03
Compounds represented by the following general formula:
[wherein X
1
, X
2
, X
3
and X
4
each independently represent a single bond, C
1-6
alkylene, etc.; A
2
represents optionally substituted phenyl, etc.; A
1
represents an optionally substituted 5- to 7-membered heterocyclic group containing —C(=Q
1
)- (wherein Q
1
represents oxygen, sulfur or ═N—R
11
(wherein R
11
represents hydrogen or C
1-6
alkyl)) and nitrogen, etc.; and Z
1
represents piperidin-diyl, etc.],
salts thereof and hydrates of the foregoing.
Quinoline derivatives having vegf inhibiting activity
申请人：——
公开号：US20030199491A1
公开（公告）日：2003-10-23
The invention relates to compounds of formula (I) wherein: either any one of G
1
, G
2
, G
3
, G
4
and G
5
is nitrogen and the other four are —CH—, or G
1
, G
2
, G
3
, G
4
and G
5
are all —CH—; Z is —O—, —NH—, —S—, —CH
2
— or a direct bond; Z is linked to any one of G
1
, G
2
, G
3
and G
4
; n is an integer from 0 to 5; m is an integer from 0 to 3; R
a
represents hydrogen or fluoro; R
b
, R
1
and R
2
are defined herein and salt thereof, process for the preparation so such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and the use of a compound of formula I in the manufacture of a medicament for the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blodded animals. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of diseases states including cancer and rheumatoid arthritis.
