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Batch Variation and Pharmacokinetics of Oral Sustained Release Melatonin-loaded Sugar Spheres in Human Subjects

  • Lee, Beom-Jin;Ryu, Seung-Goo;Choi, Han-Gon;Kim, Chong-Kook;Parrott, Keith-A.;Ayres, James-W.;Sack, Robert-L.
    • Archives of Pharmacal Research
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    • v.20 no.6
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    • pp.555-559
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    • 1997
  • The three different batches of an oral sustained release melatonin (MT) delivery system were prepared by aqueous-based fluid-bed coating of the sugar spheres for the evaluation of in vitro release characteristics and plasma concentration profiles in human subjects. The MT contents in 20% coated sugar spheres of three batches (B1, B2 and B3) were $3.3{\pm}0.08$, $2.4{\pm}0.1$ and $2.5{\pm}0.13$ mg per gram of coated sugar spheres, respectively. The release profiles of three different batches had a very similar fashion. However, the release profiles of three different batches had a very similar fashion. However, the release half-lives $(T_{50%})$ of MT from B1, B2 and B3 was $3.70{\pm}0.2$, $5.2{\pm}0.2$ and $4.9{\pm}0.07h$, respectively. Plasma concentration profiles of sustained release 0.2mg melatonin-loaded sugar spheres containing 10% immediate release melatonin in gelatin capsules (B1 and B2) were then evaluated in human subjects. The in vivo plasma concentration profies of the two batches (B1 and B2) were very similar each other and located between the physiological endogenous ranges. The time to reach the peak concentration $(T_max)$ was more advanced in case of B1 when compared to B2. However, there was no statistically significant difference in the maximum concentration $(C_max)$ and the area under the curve (AUC) between B1 and B2. The AUC of melatonin-loaded sugar spheres containing 10% and 20% immediate release MT in human subjects had a good linearity between dose and AUC, regardless of the fraction of immediate release MT, indicating the first order elimination process of MT within these doses. The current oral sustained release MT delivery system may be utilized to treat circadian rhythm disorders if it is proven to be more clinically useful when compared to immediate release MT.

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Egg Development and Morphology of Larva and Juvenile of the Konoshiro Gizzard Shad, Konosirus punctatus (전어(Konosirus punctatus)의 난발생 및 자치어 형태 발달)

  • Kim, Kwan-Seok;Han, Kyeong-Ho;Lee, Jung-Hyun;Lee, Sung-Hun;Kim, Chun-Chel;Ko, Hyun-Jung;Jeong, Kwan-Sik
    • Development and Reproduction
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    • v.11 no.2
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    • pp.127-135
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    • 2007
  • In order to monitor the developmental features of embryos, larvae, and juveniles of Konoshiro Gizzard Shad Konosirus punctatus, the fertilized eggs were gotton using artificial insemination. Konosirus punctatus were caught in Mankyung-myeon, Kimjae, Jeollabuk-do at June of 2004, and experiments were carried out in Ichthyology laboratory in Chonnam National University. Konosirus punctatus spawned draft egg from March to June. The fertilized eggs were cultured in $19.0{\sim}23.0^{\circ}C$(mean, $21.2^{\circ}C)$. The eggs had spherical shape and the diameter is $1.14{\sim}1.34\;mm$(mean, 1.21 mm). The lens began to appear from 35 hr 53 min after fertilization. At the moment, the movement of larvae was more active, and the tail was separated completely from yolk, the heart had forms, and melanophore appeared. Hatching was observed from 37 hr 10 min after fertilization. The total length of the hatched larvae was $4.26{\sim}5.30\;mm$(mean, 4.96 mm), but the mouth and anus were not opened at the time when the larva had yolk sack, and had $22{\sim}27$ myometium, and the anus located just abdominal front of the tail fin, and melanophore accumulated in the eye. Post-larvae used yolk completely after 2 day of hatching, and the total length was $4.96{\sim}5.74\;mm$(mean, 5.24 mm). From 16 days after hatching, the tail had curved tail end, and appeared the stems for pectoral, dorsal, and caudal fins. At 53 days after hatching, the total length of post-larvae was $27.11{\sim}34.09\;mm$(mean, 30.11 mm), and the frontal part of head developed like an adult one. At this time, fins and body are transferred to those of adult Konosirus punctatus. Fishes have a different shape and location of melanophore even in the same family. This research was tried to elucidate the early developmental features of Konosirus punctatus, together with species-specific pattern of melanophore.

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Modern Paper Quality Control

  • Olavi Komppa
    • Proceedings of the Korea Technical Association of the Pulp and Paper Industry Conference
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    • 2000.06a
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    • pp.16-23
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    • 2000
  • The increasing functional needs of top-quality printing papers and packaging paperboards, and especially the rapid developments in electronic printing processes and various computer printers during past few years, set new targets and requirements for modern paper quality. Most of these paper grades of today have relatively high filler content, are moderately or heavily calendered , and have many coating layers for the best appearance and performance. In practice, this means that many of the traditional quality assurance methods, mostly designed to measure papers made of pure. native pulp only, can not reliably (or at all) be used to analyze or rank the quality of modern papers. Hence, introduction of new measurement techniques is necessary to assure and further develop the paper quality today and in the future. Paper formation , i.e. small scale (millimeter scale) variation of basis weight, is the most important quality parameter of paper-making due to its influence on practically all the other quality properties of paper. The ideal paper would be completely uniform so that the basis weight of each small point (area) measured would be the same. In practice, of course, this is not possible because there always exists relatively large local variations in paper. However, these small scale basis weight variations are the major reason for many other quality problems, including calender blacking uneven coating result, uneven printing result, etc. The traditionally used visual inspection or optical measurement of the paper does not give us a reliable understanding of the material variations in the paper because in modern paper making process the optical behavior of paper is strongly affected by using e.g. fillers, dye or coating colors. Futhermore, the opacity (optical density) of the paper is changed at different process stages like wet pressing and calendering. The greatest advantage of using beta transmission method to measure paper formation is that it can be very reliably calibrated to measure true basis weight variation of all kinds of paper and board, independently on sample basis weight or paper grade. This gives us the possibility to measure, compare and judge papers made of different raw materials, different color, or even to measure heavily calendered, coated or printed papers. Scientific research of paper physics has shown that the orientation of the top layer (paper surface) fibers of the sheet paly the key role in paper curling and cockling , causing the typical practical problems (paper jam) with modern fax and copy machines, electronic printing , etc. On the other hand, the fiber orientation at the surface and middle layer of the sheet controls the bending stiffness of paperboard . Therefore, a reliable measurement of paper surface fiber orientation gives us a magnificent tool to investigate and predict paper curling and coclking tendency, and provides the necessary information to finetune, the manufacturing process for optimum quality. many papers, especially heavily calendered and coated grades, do resist liquid and gas penetration very much, bing beyond the measurement range of the traditional instruments or resulting invonveniently long measuring time per sample . The increased surface hardness and use of filler minerals and mechanical pulp make a reliable, nonleaking sample contact to the measurement head a challenge of its own. Paper surface coating causes, as expected, a layer which has completely different permeability characteristics compared to the other layer of the sheet. The latest developments in sensor technologies have made it possible to reliably measure gas flow in well controlled conditions, allowing us to investigate the gas penetration of open structures, such as cigarette paper, tissue or sack paper, and in the low permeability range analyze even fully greaseproof papers, silicon papers, heavily coated papers and boards or even detect defects in barrier coatings ! Even nitrogen or helium may be used as the gas, giving us completely new possibilities to rank the products or to find correlation to critical process or converting parameters. All the modern paper machines include many on-line measuring instruments which are used to give the necessary information for automatic process control systems. hence, the reliability of this information obtained from different sensors is vital for good optimizing and process stability. If any of these on-line sensors do not operate perfectly ass planned (having even small measurement error or malfunction ), the process control will set the machine to operate away from the optimum , resulting loss of profit or eventual problems in quality or runnability. To assure optimum operation of the paper machines, a novel quality assurance policy for the on-line measurements has been developed, including control procedures utilizing traceable, accredited standards for the best reliability and performance.

Study on the Herb Remedies of ENT, Eyes, Teeth and Skin Problems (이비인후, 안, 치아 및 피부증상의 민간요법에 관한 고찰)

  • Cho, Kyoul-Ja;Kang, Hyun-Sook
    • Journal of East-West Nursing Research
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    • v.1 no.1
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    • pp.50-71
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    • 1997
  • The intention of this study is to apprehend the con. tents and methods of herb remedies that are commonly conducted when there are health-problem cases of ENT, eyes, teeth and skin. Methods of this study are divided into two stages : 1) For a period of six months from December 1994 to June 1995, some 40 persons who are believed to be well versed with herb remedies have been randomly chosen, and we made a survey on herb remedies by symptoms: and 2) we have endeavored to make their grounds evident through the studies on literatures with the focus on the basic data collected. Their results are as follows: 1) When one feels a pain in ears, such herb remedies are employed as pouring the vapor into ears, which is made by steaming Alaska pollack, or as applying or wiping with the juices of radish or the ginkgo, or' alum. Applying the radish juice is effective for sterilization and fever removal: and applying the ginkgo juice is effective for cleanliness. But, plastering alum, sesame oil or castor oil, or pouring the vapor of Alaska pollack into ears are perhaps effective but do not have any pharmacologic grounds. 2) When one bleeds at the nose, such kinds of herb remedies are applied as stimulating nose or head with cold water, pressing nose or ridge of nose, or filling up nares with mashed mugworts. In addition, they have utilized garlic or leeks. Such methods as stimulating with cold water or just pressing nose and ridge of nose is based on reasonable grounds, i.e. vasoconstriction and vascular compression ; and applying mashed garlic on the sole of foot is good for the circulation of Qui ; and the use of mugworts and leeks is based upon the pharmacological function of hemostasis. 3) When one feels a sore throat such kinds of herb remedies are employed as gargling or rinsing throat with brine, drinking hot gruel or water, or drinking the juice of mugwort, radish, ginger or Chinese quince. Gargling with brine or drinking the juice of mugwort, radish or ginger is based upon the pharmacological function of pain alleviation, fever removal, and detoxication. 4) When a boil is formed in mouth, such herb remedies are applied as spreading honey, brine or alum water, and taking gall nut, Chinese matrimony vine, lotus root, etc, for drugs. Spreading honey, brine or water that is made by infusing gallnut, Chinese matrimony vine, lotus root is based upon such functions as hematosis, astriction, antibacterial, and antiphlogistic, Alum, eggplant and licorice are said to be effective, but their pharmacological effects have no grounds. 5) When one has conjunctivitis such herb remedies are commonly applied as irrigation with brine and dropping breast milk in eyes. Moreover, such other drugs are used as plantain. shepherd's purse, and purslane, etc. The use of brine, breast milk, plantain, shepherd's purse and purslane is based upon such functions as sterilization, antiphlogistic, disinfection and pain relieving. Eriocaulon sieboldianum, bean stem, bean pod and narcissus leaves are said to be effective, but their pharmacological action have no basis. When one has a stye, such herb remedies are applied as extracting eyelashes, stimulating by a massage of middle finger, third finger or big toe, as well as sear ing with a heated bamboo comb that is fine-toothed. Other than these, plantain and nightshade's nuts are used as drugs for it. Extracting eyelashes corresponds with exclusing suppurative node and draining the stye of pus ; and the use of plantain is based upon disinfection: and nightshade's nuts are said to be effective, however, their pharmacological action has no grounds. 6) For a treatment of toothache, such herb remedies are commonly employed as rinsing mouth with brine and holding cold water or gasoline in the mouth ; and as the drugs that are believed to be effective have been Welsh onion, ginger and castor-oil, plant, etc. The use of Welsh onion is based upon pain killing, antiinflammatory actions, and the use of ginger is based upon detoxication and disinfection ; and seeds of castor-oil plants are said to be effective, but they have no pharmacological basis. 7) When one has hives, such herb remedies are commonly applied as rubbing burned straw in affected parts, exposing to its smoke, rubbing with salt, sweeping down with a broom, and spreading and drinking boiled water of trifoliate orange. The use of cassia tora seeds, walnut, aloe and radish is said to be effective. The use of cassia tor a seeds has the functions of intestinal order, anti-paralysis, etc. The use of walnut has resulted in an increase of blood by invigorating spirits ; and the use of aloe is based upon disinfection, antibiotic, anti-salt, antihistamine and detoxication action. But, the effects of radish juice and straw's smoke have no pharmacological grounds. 8) When one gets a boil, such herb remedies are commonly used as applying a plaster, paste of flour mixed with yolk, soy sauce or honey, as well as spreading pounded elm tree. Other remedies that have been said to be effective are ; heating with mugwort, brine, wild rocambole, aloe, onion, squid's bone, etc. The use of mugwort is based upon pain killing, astringent antiinflammatory and tranquility. Wild rocambole is based upon the generation and maintenance functions of cell-joining textures ; elm tree upon antiphlogistic ; aloe upon fever removal and antiphlogistic ; onion on pain killing, fever removal, antiphlogistic and tranquility ; squid's bone on astriction: and brine or vinegar on sterilization. Pine resin and gardenia seed are said to be effective, but they have no pharmacological basis. 9) When one cuts his skin, such herb remedies are commonly employed as spreading mugwort's juice or squid's bone powder, or pressing the wounds. In addition, kalopanax, onion and fine soil are employed. The use of mugwort, kalopanax and squid's bone is based upon such functions as hemostasis, sedation, pain killing, antibacterial ; and fine soil is said to be effective, but it has no pharmacological basis. 10) When one suffers from whitlow, such herb remedies are commonly utilized as heating with boiled soy sauce, spreading soybean paste, or dipping into eggs, etc. Other drugs that have been employed are onion root, brine, eggplant, potato, loach, etc. The use of onion is based upon pain killing and antiphlogistic functions ; and that of brine upon antiphlogistic function. The use of soy sauce or soybean paste, fomentation, eggplant, potato and loach is said to be effective, but it has no pharmacblogic ground. 11) For the treatment of frostbite, such herb remedies are commonly used as dipping the affected part into frozen soybean sack, using boiled water of eggplant stem, garlic caulis, onion, hot pepper, caulis. Onion is based upon antiphlogistic and tranquility actions garlic upon disintection, metabolic exacerbation, tonic and aphrodisiac actions and the use of eggplant and hot pepper is based upon help blood circulation, dissolution and excretion of waste matters in vein. 12) For the treatment of burn, such herb remedies or drugs are commonly used as cleansing with Korean gin, spreading eggs, cleansing with cold water and soap water ; and as brine, cactus, moss, soybean paste, oil, etc. The cleansing with Korean gin, cold water, soap water, brine, vinegar is based upon cleaning and sterilizing functions ; and the use of cucumber is based upon nu. trition provision, and strengthening of resisting power by adjustment of metabolism. The use of potato, cactus, moss, oil and eggs is said to be effective, but their phamacological functions are not clarified. In view of the above results, we can realize that the drugs that have been employed in herb remedies are quite diverse. However, in regard to majority of herb remedies that have been employed by symptoms, the pharmacological functions of their drugs have not been clarified, and they are merely known as effective. Furthermore, they have not been recorded in the literature as yet ; and we confirm that there have been many herb remedies that were executed without the proper knowlege of their effects. It is now our view that the results of this survey may be utilized for consulting data in regard to the use of herb remedies.

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