National Institute on Drug Abuse research monograph series最新文献

National Institute on Drug Abuse research monograph series Pub Date : 1976-10-01

M Bateman

引用次数: 0

National Institute on Drug Abuse research monograph series Pub Date : 1976-10-01

L N Robins

引用次数: 0

Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists. 合成多肽在制备麻醉拮抗剂可生物降解递送载体中的应用。

National Institute on Drug Abuse research monograph series Pub Date : 1976-01-01

K R Sidman, D L Arnold, W D Steber, L Nelsen, F E Granchelli, P Strong, S G Sheth

{"title":"Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists.","authors":"K R Sidman, D L Arnold, W D Steber, L Nelsen, F E Granchelli, P Strong, S G Sheth","doi":"","DOIUrl":"","url":null,"abstract":"Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10-7 cm2/hr to 120 x 10-7 cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphene sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.","PeriodicalId":76198,"journal":{"name":"National Institute on Drug Abuse research monograph series","volume":" 4","pages":"33-8"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12149878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

History of drug use. 药物使用史。

National Institute on Drug Abuse research monograph series Pub Date : 1976-01-01 DOI: 10.1037/e497482006-004

L. Robins

引用次数: 10

Testing of drug delivery systems for use in the treatment of narcotic addiction. 用于麻醉成瘾治疗的药物输送系统的试验。

National Institute on Drug Abuse research monograph series Pub Date : 1976-01-01

R H Reuning, L Malspeis, S Frank, R E Notari

{"title":"Testing of drug delivery systems for use in the treatment of narcotic addiction.","authors":"R H Reuning, L Malspeis, S Frank, R E Notari","doi":"","DOIUrl":"","url":null,"abstract":"The evaluation of the drug release characteristic of four naltrexone delivery systems has been carried out together with the development of analytical techniques and an investigation of the metabolic profile of naltrexone. Pharmacologic evaluation of the four delivery systems in the mouse indicated significant analgesic antagonism for a period of from 16-22 days. Further evaluation of one of these systems by measurement of the rate of excretion of radioactivity after administration of radiolabelled naltrexone in the delivery system confirmed that significant release occurs for a time period of about 15 days. Electron capture gas-liquid chromatographic assays for naltrexone and naloxone in plasma or urine have been developed that yield linear calibration curves and are sensitive to one ng/ml. Studies on naltrexone disposition indicate that (a) binding to plasma proteins in several species varies from 20-26%, (b) distribution of drug from blood is extremely rapid and extensive, (c) beta-naltrexol is a major metabolite of naltrexone in man, monkey and guinea pig among six species studies, whereas alpha-naltrexol is a minor metabolite in the monkey and guinea pig only, and (d) metabolic reduction of naltrexone occurs in the 100,000 x g supernatant of guinea pig liver. Pharmacokinetic studies of naltrexone in the dog and monkey indicate that the drug is rapidly distributed and eliminated, has a very large apparent volume of distribution and a total body clearance greater than the rate of liver blood flow.","PeriodicalId":76198,"journal":{"name":"National Institute on Drug Abuse research monograph series","volume":" 4","pages":"43-5"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12008783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of injectable microcapsules for use in the treatment of narcotic addiction. 麻醉成瘾治疗用注射微胶囊的研制。

National Institute on Drug Abuse research monograph series Pub Date : 1976-01-01

C Thies

引用次数: 0

Development of Chronomers tm for narcotic antagonists. 麻醉拮抗剂Chronomers tm的研究进展。

National Institute on Drug Abuse research monograph series Pub Date : 1976-01-01

R C Capozza, E E Schmitt, L R Seńdelbeck

{"title":"Development of Chronomers tm for narcotic antagonists.","authors":"R C Capozza, E E Schmitt, L R Seńdelbeck","doi":"","DOIUrl":"","url":null,"abstract":"The object of this program is to prepare a bioerodable naltrexone delivery system which can be implanted subcutaneously in humans and which can relieve the narcotic antagonist over 1-6 months at relatively constant and sufficient rates to block the euphoric effect of morphine based drugs. The system is composed of naltrexone uniformly dispered in a solid hydropholic CHRONOMER TM matrix which undergoes predictable surface erosion when exposed to an aqueous medium. Kinetic studies in vitro have been carried out during the course of the program to determine the best composition for the system. Toxilogical studies conducted at ALZA during the past 2 years have not revealed limiting adverse effects of either the CHRONOMER TM materials or their hydrolysis products. The tail-flick test procedure was used to measure the effectiveness of naltrexone to antagonize the analgesis of morphine in rats. Naltrexone infused intravenously at doses of 4 and 16 ug/kg/hr resulted in, after 6 hours, 54 and 89% antagonism, respectively, against a 63.5% effective dose of morphine. Perliminary sterilization studies showed that no adverse effects to CHRONOMER TM/naltrexone systems occurred after exposure to 2.5 or 5.0 mrads of 60CO irradiation.","PeriodicalId":76198,"journal":{"name":"National Institute on Drug Abuse research monograph series","volume":" 4","pages":"39-42"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12149879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-acting narcotic antagonist complexes. 长效麻醉拮抗剂复合物。

National Institute on Drug Abuse research monograph series Pub Date : 1976-01-01

A P Gray, W J Guardina

{"title":"Long-acting narcotic antagonist complexes.","authors":"A P Gray, W J Guardina","doi":"","DOIUrl":"","url":null,"abstract":"We evaluated the ability of close to 100 organic acids to form water-soluble salts with methadone, cyclazocine, naloxone, naltrexone and, more recently, diprenorphine. About half the acids yielded insoluble salts. Polybasic acids affording insoluble salts were evaluated for their ability to form drug:acid:metal complexes with the polyvalent metal ions, Zn++, Al+++, Mg++ and Ca++. Optimum conditions for forming complexes have been developed and the consistency of their composition has been established. Salts were analyzed spectrophotometrically for drug content, and complexes were analyzed for drug and metal content. The in vitro degree of dissociation at equilibrium was measured for the preparations suspended in a simulated physiological buffer, pH 7.3. Preparations of the narcotic antagonist drugs showing relatively low degrees of dissociation in vitro, since it early appeared that a high degree of dissociation contraindicated a prolonged duration of pharmacological action, were evaluated in mice after intramuscular administration at several dose levels by the mouse tail-flick test for the potency and duration of their morphine antagonist activity. Our most promising preparations to date, showing the most prolonged durations of action without evidence of gross toxicity, are naltrexone zinc tannate and naltrexone aluminum tannate. These are undergoing detailed evaluation as potential clinical candidates. Thus far, the most useful of several dosage forms studied is a suspension in an aluminum monostearate gel.","PeriodicalId":76198,"journal":{"name":"National Institute on Drug Abuse research monograph series","volume":" 4","pages":"21-6"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12149876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sustained release of naltrexone from glyceride implants. 甘油植入物中纳曲酮的缓释。

National Institute on Drug Abuse research monograph series Pub Date : 1976-01-01

M F Sullivan, D R Kalkwarf

引用次数: 0

Development of polylactic/glycolic acid delivery systems for use in treatment of narcotic addiction. 用于麻醉成瘾治疗的聚乳酸/乙醇酸递送系统的研制。

National Institute on Drug Abuse research monograph series Pub Date : 1976-01-01

A D Schwope, D L Wise, J F Howes

{"title":"Development of polylactic/glycolic acid delivery systems for use in treatment of narcotic addiction.","authors":"A D Schwope, D L Wise, J F Howes","doi":"","DOIUrl":"","url":null,"abstract":"Implantable polylactic/glycolic acid matrix systems have successfully provided the sustained release of naltrexone to mice for periods of up to 200 days. In vitro and in vivo release rates have been determined by measuring chemical concentrations in pH 7 buffer solution and urine, respectively, and in vivo efficacy has been measured by direct challenge with morphine (Dewey-Harris mouse tail-flick test). Dosage forms of small implantable cylinders, 1/16'' diameter, (25 mg/rod, one rod/mouse) containing 33% by weight naltrexone pamoate in 90 L(+)/10 polylactic/glycolic acid have sustained the delivery of chemical for 20 days. Delivery of chemical from dosage forms of 1/16'' diameter spherical beads (3 mg/bead, 3 beads/mouse) containing 33% by weight naltrexone base in 90 L(+)/10 polylactic/glycolic acid was sustained for 60 days. Earlier a similar bead type dosage form of 75 L(+)/25 polylactic/glycolic acid containing 50% by weight naltrexone base and coated with the pure polymer provided controlled release for 25 days. Polymerization conditions which incorporate the use of pharmacologically suitable catalysts and yield products reproducibly have have been delineated. Techniques for sterilization of the final implant have been screened.","PeriodicalId":76198,"journal":{"name":"National Institute on Drug Abuse research monograph series","volume":" 4","pages":"13-8"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11978849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0