复方福尔可定糖浆用于镇咳的疗效及安全性评价

目的：评价复方福尔可定糖浆用于镇咳的临床效果及安全性。方法：采用多中心随机双盲对照试验设计，以联邦止咳露为对照。患者每次口服10-15ml，每日3次，连用3-7d。结果：共完成试验196例，其中试验组99例，对照组97例，复方福尔可定糖浆临床止咳总有效率为76.8%，祛痰总有效率为48%，与联邦止咳露无显著性差异。主要药物不良反应主另轻微嗜睡、心悸，发生率较低与对照组类似。结论：每次口服复方福尔可定糖浆10-15ml，每日3次，可达到良好的镇咳效果，药物不良反应发生少，较为安全可靠。     

Antitussive properties of levodropropizine

The antitussive activity of levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in anaesthetized guinea-pigs and rabbits and in unanaesthetized guinea-pigs. Levodropropizine was shown to have good antitussive activity. Intravenously, it was 1/10 to 1/20 as active as codeine and comparable to dropropizine, from which it is derived, on mechanically and electrically induced coughing in rabbits and guinea-pigs. After oral administration to the guinea-pig the antitussive activity of levodropropizine was comparable with those of both dropropizine and codeine against coughing induced by irritant aerosols.     

Antitussive effect of dihydroetorphine in mice

The present study examined the opioid receptors involved in the antitussive effect of dihydroetorphine in mice. Dihydroetorphine suppressed coughs dose dependently at doses between 0.1–1 μg/kg i.p. Blockade of μ-opioid receptors by pretreatment with β-funaltrexamine significantly reduced the antitussive effect of dihydroetorphine. Furthermore, the antitussive effect of dihydroetorphine was also antagonized by nor-binaltorphimine, a κ-opioid receptor antagonist. However, pretreatment with naltrindole, a δ-opioid receptor antagonist, did not affect the antitussive effect of dihydroetorphine. These results indicate that the antitussive effect of dihydroetorphine is mediated by the activation of μ-opioid receptors and κ-opioid receptors, but not δ-opioid receptors.     

Evaluation of Retinoids as Therapeutic Agents in Dermatology

Evaluation of 13-cis-12-substituted analogues of retinoic acid in a series of dermatologic screens has revealed that structural modifications can lead to selectivity and specificity. An analogue, 11-cis,13-cis-12-hydroxymethylretinoic acid, -lactone, has been found to have good activity and to be devoid of topical and systemic toxicity.     

Patent Evaluation: Fluoroquinolone Antibacterial Agents

Summary

Novelty: Novel quinoline, naphthyridine and pyridobezoxazine derivatives are disclosed. The compounds are potentially useful against microbial pathogens.

Biology: The antibacterial activity of the compounds is demonstrated against a wide variety of bacteria including Staphylococcus aureus, Micrococcus leuteus and Pseudomonas aeruginosa. Additionally, the in vivo antibacterial activity of a specific compound is determined by studying the protection of CF-1 female mice from bacterial challenge (Staphylococcus aureus). An oral ED₅₀ of 6.0 mg/kg/day and a subcutaneous ED50 of 5.0mg/kg/day is obtained.

Chemistry: Thirty-three compounds are specifically claimed. Two of the specifically claimed compounds are 1-cyclopropyl-6,8-difluoro-7-(9-amino-1,4-dioxa-7-azaspiro [4,4]non-7-yl)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid and 7-(2-didimethylaminomethyl-1,4-dioxa-7-azaspiro[4.4]non-7-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,8-napthyridine-3-carboxylic acid. The preparation of 552 compounds is either directly or indirectly exemplified. The preparative process is not claimed.     

Patent Evaluation: Novel Antifungal Agents

Summary

Novelty: Novel fungicidal compositions comprising a pyranyl ester and a β-lactone are disclosed. A method for controlling mycotic infections is also given.

Biology: The MIC against Candida albicans was determined to be 3.1μg/ml for β-lactone dienoic acid and 2μg/ml for the pyranyl glycine ester.

Chemistry: The pyranyl glycine esters are either (2,3,4,5)-tetrahydro-4-methoxy-5-methyl-2-(1-methyl-1,3,5-nonatrienyl)-2-pyran-3-yl glycine or (2,3,4,5)-tetarahydro-4-methoxy-5-methyl-2-(1-methyl-1,3,5-nonatrienyl)-2-pyran-3-yl-N,N-dimethylglycine. The preferred β-lactone is 11-(3-hydroxymethyl-4-oxo-2-oxetanyl)-7-methyl-2,4-undecadienoic acid.

Structure:      

Patent Evaluation: Hydroxyurea Anti-Inflammatory Agents

Summary

Novelty: N-hydroxyureas are disclosed which are inhibitors of 5-lipoxygenase (5-LPO) and are potentially useful for the treatment of inflammatory disorders, such as asthma.

Biology: The ability of the compounds to inhibit 5-LPO was demonstrated using a rat peritoneal macrophage assay. IC₅₀ values are said to be between 0.01-30μM; no specific data are presented.

Chemistry: The compounds of the invention were prepared from the appropriate oxazole (thiazole) carboxaldehyde. Seven examples are given, all of which are specifically claimed, including N-hydroxy-N-[(2-phenyloxazol-4-yl)methyl]urea.     

Patent Evaluation: Benzodithiazole Antifungal Agents

Summary

Novelty: Eighty-one novel substituted 1,3,2-benzothiazole-1-oxides are listed; forty-three of the compounds are additionally substituted in the benzene ring. The compounds are claimed as antifungal agents.

Biology: Activities determined in vitro by broth dilution against ten strains of fungi (seven Candida species and one species each of Torulopsis glabrata, Cryptococcus albidus and Aspergillus niger) are given for thirty-four of the compounds; five favourably compare with the amphotericin B standard and are specifically claimed. No indication is given of activity in vivo or of freedom from toxicity.

Chemistry: Forty-one compounds are exemplified by synthesis. Nearly seventy compounds are specifically claimed; only five of these are claimed for the synthesis of an antifungal preparation, including 2-n-heptyl-1,3,2-benzodithiazole-1-oxide.

Structure:      

Patent Evaluation: Benzodioxan Antipsychotic Agents

Summary

Novelty: Novel aminophenoxyalkyl derivatives of benzodioxan are disclosed and are claimed to be antipsychotic, antidepressant and anxiolytic agents. They are useful in the treatment of multi-CNS disease states.

Biology: The effect of the compounds on the synthesis of dopamine was determined using the method of Walters (Naunyn-Schmiedeberg's Arch. Pharmacol. (1976) 296:5-14). The antipsychotic activity of these compounds was determined using the method of Martin (J. Pharmacol. Exp. Therap. (1984) 229:706-711). The affinity for the dopamine D₂ receptor was also assayed for the compounds using the method of Fields (Brain Res. (1977) 136:578). Affinity for the 5HT_1A receptor was determined by the method of Hall et al. (J. Neurochem. (1985) 44:1685). The specified compound gave 64% (limbic) and 66% (striatal) inhibition of 0.15 mg ip and receptor affinities (IC₅₀) of 51 nM (D₂) and 8 nM (5HT_1A). Results for nineteen compounds are presented in a table.

Chemistry: Synthesis of the compounds are described in nineteen examples. N-[3-(3-aminophenoxy)propyl]-2,3-dihydro-7-hydroxy-1,4-benzodioxin-2-metanamine is one of fifteen specifically claimed compounds.     

Patent Evaluation: Guanidine-like Anti-arrhythmic Agents

Summary

Novelty: Novel aryl-fused and hetaryl-fused 2,4-diazepines, benzodiazocines and benzodiazepines are said to possess anti-arrhythmic activity. Some novel intermediates which are used in the preparation of the inventive compounds are also disclosed.

Biology: Anti-arrhythmic activity was demonstrated using electrophysiological techniques in guinea pigs. In an assay to assess the dose which causes a 20% increase in the effective refrectory period (ERP). The most active compounds had ED₂₀ values of 0.01 to 0.05 mg/kg.

Chemistry: (R)-(+)-4,5-Dihydro-4-methyl-1-phenyl-3-(2-phenylethyl)-1H-2,4-benzodiazepine is one of eleven specifically claimed compounds.

Structure:      

Patent Evaluation: Leustroducsin Antifungal Agents

Summary

Novelty: Leustroducsins A, B and C have been isolated from a new non-pigmented strain of Streptomyces platensis. They appear to be distinct from similar pyranone derivatives isolated from S. platensis SAM-0654 or phospholine produced by S. hygroscopicus.

Biology: These leustroducsins have been shown to stimulate GM-CSF and G-CSF production by KM-102 cells and nerve growth factor production by L-M cells in vitro. A direct antifungal effect has been demonstrated quantitatively in vitro using Trichophyton mentagrophytes. Based on these limited observations, claimed are made for utility in the treatment or prophylaxis of adverse reactions resulting from cancer chemotherapy or radiotherapy, infections, cancer, cerebral dysfunction and fungal infections.

Structure:      

Patent Evaluation: Erythromycin Antibacterial Agents

Summary

Novelty: A novel method of preparing novel 9-deoxo-8a-aza-8a-homoerythromycin A and its 8a-alkyl derivatives, and 8a-aza-8a-homoerthythromycin cylic iminoethers is claimed. The compounds are antibiotics and may be used to treat bacterial infections; they may also be used as intermediates for the synthesis of other compounds.

Biology: Antibacterial activity of two compounds was assayed against fifteen bacterial strains in vitro. MIC values were determined turbidimetrically in brain heart infusion broth and are 0.06 to 128 μg/ml for the preferred compound. The spectrum of activity of the compounds is said to be similar to erythromycin A. Their in vivo activity is more limited, although they are active against Gram-positive and certain Gram-negative bacteria.

Chemistry: Synthesis is by multistep reactions by standard techniques, starting from 8a-aza-8a-homoerythromycin cyclic iminoethers (in EP-508726-A) and 9-deoxy-9(Z)-hydroxyiminoerythromycin A (in EP-508725-A). Eleven examples are given in each application. Characterization is by mp, IR, NMR, MS and elemental analysis. The preferred compound is 9-deoxo-8a-methyl-8a-aza-8a-homoerythromycin A (in EP-508726-A) and 9-deoxy-6,9-epoxy-8a,9-didehydro-8a-aza-8a-homoerthromycin A (in EP-508725-A).     

促胃肠动力药的进展与临床评价

目的：了解胃肠道促动力剂的最新动态。方法：查阅国内外文献,结合基础研究成果对各种药物在治疗消化不良中的地位和疗效进行讨论。结果及结论：胃肠促动力药具有疗效好、不良反应少等特点,除用于消化不良外,尚可治疗食管反流性疾病、慢性胃炎、便秘等,在胃肠疾病的治疗中显示出良好的前景。     

Influence of Chinoin-170, a Novel Antitussive,on the Mucociliary Activity in Respiratory Airways of Rats,Rabbits, Guinea-pigs and Man

Abstract— Chinoin-170 (Ch-170; 3,7-dihydro-1,3-dimethyl-7-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]1H-purine-2,6-dione) is a new antitussive with bronchodilating activity. Its effects on the ciliary beating frequency (CBF) and mucociliary clearance were studied. In tracheal explants of rats, Ch-170 dose-dependently at concentrations 2 and 5 mg mL^?1 depressed CBF by 24 and 33%, respectively. In human mucosal explants, however, no effects were seen at concentrations up to 5 mg mL^?1. In anaesthetized guinea-pigs, an intravenous 50 mg kg^?1 dose of Ch-170 caused no changes, and 100 mg kg^?1 increased the CBF by 15%. Intravenous Ch-170 dose-dependently increased by 93 (50 mg kg^?1), 179 (70 mg kg^?1) and 253% (100 mg kg^?1) the tracheobronchial mucociliary clearance in rabbits. The effect, studied using ^99mTc-labelled red blood cells as a marker, was of similar quantity to that brought about by administering 16, 25 and 40 mg kg^?1 doses of bromhexine. It is concluded that unlike many older antitussives, Ch-170 in-vitro only slightly decreases the CBF in rats and has no adverse effects on the CBF in human mucosal explants at concentrations up to 5 mg mL^?1. In-vivo, Ch-170 does not significantly alter the CBF in guinea-pigs, but dose-dependently increases the mucociliary clearance in rabbits. The increase is most probably a result of changes in the production and the properties of respiratory mucus.     

In-vivo Evaluation in Man of a Hydrophilic Matrix Containing Propylthiouracil

To reduce the number of administrations of propylthiouracil required to treat hyperthyroidism, the bioavailability and sustained-release characteristics of 300 mg propylthiouracil formulated in hydrophilic matrix tablets were evaluated after single oral administration in healthy male volunteers. A conventional tablet was chosen as the reference formulation. For tablets formulated from three different types of hydroxypropylmethylcellulose, K15M, K4M and K100LV, propylthiouracil dissolution in-vitro was 40%, 51% and 100%, respectively, in 8 h. The three matrix formulations showed sustained plasma concentration-time profiles. The relative bioavailability was 50, 51 and 87%, respectively, for K4M, K15M and K.100LV hydroxypropylmethylcellulose matrix tablets. When reverse triiodothyronine concentrations were plotted against the corresponding propylthiouracil concentrations, an antihysteresis loop was observed with the conventional tablets and the K100LV matrix tablet. A linear concentration-response curve was obtained for both the K4M and K15M formulations. The results showed that the K100LV matrix tablet gave a sustained plasma concentration-time profile and a bioavailability and extrathyroidal effect similar to that of a conventional tablet.     

和肤洗剂中抑菌剂的抑菌效力评价

目的:探索适用和肤洗剂的抑菌剂及其最适浓度.方法:山梨酸钾、苯甲酸钠、羟苯乙酯三种抑菌剂结合不同浓度,考察其抑菌效力,筛选出适宜的抑菌剂以及浓度.参照《中国药典》2015年版四部通则1121抑菌效力检查法的相关规定进行研究试验,测试不同抑菌剂不同浓度对微生物的抑制情况.结果:0.2％苯甲酸钠、苯甲酸钠0.1％+羟苯乙酯...