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1. 发明申请

WO2019169141A1 PRODUCTION AND USE OF EXTRACELLULAR VESICLES 审中-公开
公开(公告)号：WO2019169141A1
公开(公告)日：2019-09-06
申请号：PCT/US2019/020064
申请日：2019-02-28
申请人： LESTER SMITH MEDICAL RESEARCH INSTITUTE
发明人： CORONADO, Ramon
IPC分类号： A61L15/44 , A61K35/28 , A61K35/48 , A61K35/545 , A61K38/12 , A61K38/16 , A61K38/18 , A61P35/04 , C12N15/88
摘要： The invention provides a method of producing and using extracellular vesicles (ECVs) derived from activated stromal cells for the treatment of certain disease and conditions. Specifically, ECVs derived from preactivated mesenchymal cells are effective in reducing cancer cell growth and metastasis as well as inducing tolerogenesis in immature dendritic cells. Additionally, ECVs derived from umbilical cord blood may be useful for immunosuppression and reduction of inflammation.

2. 发明申请

WO2017197016A1 MELATONIN-BASED NASAL COMPOSITIONS AND USES THEREOF 审中-公开
标题翻译：基于褪黑素的鼻用组合物及其用途
公开(公告)号：WO2017197016A1
公开(公告)日：2017-11-16
申请号：PCT/US2017/032008
申请日：2017-05-10
申请人： THE LESTER SMITH MEDICAL RESEARCH INSTITUTE, LLC
发明人： CORONADO, Ramon
IPC分类号： A61K9/00 , A61K31/4045 , A61K31/405 , A61P25/20
摘要： Disclosed is an improved composition characterized in containing a combination of melatonin and 5-HTP in a nasal administration for the rapid treatment of insomnia, anxiety, and related disorders in mammals, including humans. The present invention relates also to a pharmaceutical composition comprising 5-HTP and melatonin which utilizes the known effects of two substances to provide sleep improvement, relaxation, and reduced anxiety via rapid delivery of the combination, via nasal administration, for short-term alleviation of sleep disorder and anxiety-related symptoms. The combined effects of 5-HTP and melatonin in the present invention provide a short-term increase in blood plasma levels of melatonin while simultaneously increasing the production of serotonin for purposes of achieving natural melatonin biosynthesis in combination with the increased melatonin content in blood plasma.
摘要翻译：公开了一种改进的组合物，其特征在于在鼻腔施用中含有褪黑激素和5-HTP的组合，用于快速治疗哺乳动物包括人的失眠，焦虑和相关病症。本发明还涉及包含5-HTP和褪黑激素的药物组合物，其利用两种物质的已知作用通过经鼻施用快速递送组合以提供睡眠改善，松弛和减轻的焦虑，用于短期缓解睡眠障碍和焦虑相关症状。本发明中5-HTP和褪黑激素的联合作用提供了褪黑激素的血浆水平的短期增加，同时增加了血清素的产生，以实现天然褪黑激素生物合成并结合血浆中褪黑激素含量的增加。

3. 发明专利

GB606482A Improvements in and relating to the purification of penicillin salts 未知
公开(公告)号：GB606482A
公开(公告)日：1948-08-13
申请号：GB274046
申请日：1946-01-28
申请人： GLAXO LAB LTD , ERNEST LESTER SMITH , AUSTIN ERNEST BIDE
IPC分类号： C07D499/00 , C07D499/24
摘要： Pure penicillin is prepared by a process in which free penicillin dissolved in a solvent is treated with a primary amine. The resultant precipitate of a penicillin primary amine salt may be converted into corresponding metallic salts. It has been found desirable to dissolve the penicillin in a main solvent, subsequently to add a secondary solvent and finally to add the primary amine. Suitable primary amines are cyclohexylamine, 2, 3 or 4 methyl cyclohexyl amine, monoethylamine, isopropylamine and n-butylamine. Preferred main solvents are ether, amyl acetate, methyl isobutyl ketone and, using a modified process, chloroform. Preferred secondary solvents are ethyl alcohol, acetone and methyl ethyl ketone. In examples: (I) and (IV) an ethereal extract of an acidified penicillin solution was diluted with acetone and treated with cyclohexylamine; (II) the cyclohexylamine salt was similarly prepared using methyl isobutyl ketone as the solvent, and (III) the isopropylamine salt was prepared using ether as the main solvent with acetone as a secondary solvent.

4. 发明专利

GB604563A Improvements in and relating to the purification of penicillin salts 未知
公开(公告)号：GB604563A
公开(公告)日：1948-07-06
申请号：GB3203245
申请日：1945-11-27
申请人： GLAXO LAB LTD , AUSTIN ERNEST BIDE , WILLIAM GRAHAM , ERNEST LESTER SMITH , PETER ALFRED WILKINSON
IPC分类号： C07D499/00 , C07D499/26
摘要： Salts of penicillin of a high degree of purity are prepared by dissolving a crude metallic (preferably sodium or calcium) salt of penicillin (preferably of not less than 20 per cent purity) in water (preferably in such quantity as to give a concentration of about 1 per cent w/v.), acidifying (preferably to about pH 2.5) with a strong acid, and combining the liberated penicillin acid with one or more tertiary organic bases selected from N-alkylated piperidines, with or without one or more methyl groups as substituents on the carbon atoms of the ring, or N-alkylated pyrrolidines, with or without one or more methyl or ethyl groups (or both) as substituents on the carbon atoms of the ring, the total number of exocyclic carbon atoms in either case not exceeding 5. Preferably, the free penicillin is extracted, before combination with the base, into a suitable solvent (i.e. one into which penicillin can be extracted readily from acidified aqueous solution and which is relatively inert to penicillin, and in which the tertiary base salts of penicillin are relatively insoluble), preferably so as to give a concentration of penicillin therein of 0.25-5 per cent w/v, and advantageously after adding to the aqueous solution a highly soluble neutral inorganic salt commonly used for salting out purposes, and there is added to the extract a suitable secondary solvent (capable of retaining the tertiary base salts of the impurities in solution). As an alternative or in addition to adding the secondary solvent, the precipitate subsequently produced by the addition of at least (and usually considerably more than) one molar equivalent of the tertiary base or bases is washed with (or crystallized from) the secondary solvent or a mixture thereof with the first solvent, and may, if desired, be further purified by recrystallization from an organic solvent or mixture of solvents. To obtain a metal salt of penicillin of a similar high degree of purity, an aqueous solution of the tertiary base salt is treated with a mineral acid, the liberated penicillin is extracted into an organic solvent, and there is added to the extract an aqueous solution or suspension of a metallic hydroxide. In examples: (1) crude penicillin sodium or calcium salt is dissolved in ice-cold water with the addition of sodium chloride followed by ether and then by dilute phosphoric acid, the ether layer is separated the residue extracted with more ether, the combined ethered extracts filtered at -80 DEG C. and shaken with charcoal which is separated by filtration and eluted with ether, then acetone is added to the eluate, followed by a solution of N-ethyl-piperidine in ether, the precipitated salt is filtered off, washed with acetone, dried, and recrystallized if desired by dissolving in warm methylene chloride, adding acetone and then slowly adding carbon tetrachloride; the product may be converted into the pure sodium salt by dissolving it in ice-cold water, shaking with chloroform while adding dilute phosphoric acid, again extracting the aqueous layer with chloroform, neutralizing the combined extracts with aqueous sodium hydroxide, freeze-drying and crystallizing from acetone; (2) the ethereal solution obtained as in (1) is treated with N-n-propylpiperidine, either with the preliminary addition of acetone or with recrystallization of the precipitated salt therefrom; (3) crude penicillin calcium salt is treated as in (1) but using methyl isobutyl ketone instead of ether; (4) crude penicillin calcium salt is treated as in (1) but using methyl ethyl ketone as the secondary solvent and N-ethylhexahydro-a -picoline as the base; (5) the N-ethylpiperidine in (1) is replaced by N-ethylpyrrolidine. Amyl acetate is additionally specified as a suitable first solvent, and sodium nitrate, sodium sulphate, ammonium sulphate, magnesium sulphate and potassium chloride as salting out agents.

5. 发明专利

GB586930A Improvements in or relating to the manufacture of penicillin 未知
公开(公告)号：GB586930A
公开(公告)日：1947-04-08
申请号：GB1328844
申请日：1944-07-11
申请人： GLAXO LAB LTD , BRITISH DRUG HOUSES LTD , AUSTIN ERNEST BIDE , THOMAS HOBSON MEAD , ERNEST LESTER SMITH , MAURICE VINCENT STACK
摘要： A process for the manufacture of Penicillin comprises growing Penicillium notatum or other Penicillin producing mould on a synthetic culture medium or a medium comprising corn steep liquor to which has been added a substance of the general formula R.C6H4.CH2Y where R represents a hydrogen atom or a para hydroxyl group and Y is a carboxylic acid, carboxylic acid amide, an aldehyde or an aminomethyl (-CH2NH2) group or some other group which under the prevailing conditions of biological growth is readily convertible into one or other of these groups. Specified substances of this type are b -phenylethylamine, b -para-hydroxyphenylethylamine, b -phenyl-a -alanine, phenyl pyruvic acid, phenylacetronitrile, c-phenyl-acetamidine, phenylacetylglycine, phenylacetic acid, phenyl acetamide and phenyl acetaldehyde, and in the cases in which these are acids or bases they may be added as salts. The culture media may comprise glucose, lactose, or corn steep liquors to which may be added salts such as sodium nitrate, sodium citrate, sodium sulphate, magnesium sulphate, potassium dihydrogen phosphate, potassium iodide, ferrous sulphate, cupric sulphate, zinc sulphate, manganese sulphate, ammonium molybdate and vanadium trichloride, boric acid and also hydrolysates from zinc and casein and cystine, or protein hydrolysates rich in cystine. The process may be applied to tray, bottle, column or submerged culture.

6. 发明专利

GB668076A Improvements in or relating to boxes adapted to contain powdered material 未知
公开(公告)号：GB668076A
公开(公告)日：1952-03-12
申请号：GB2481748
申请日：1948-09-22
申请人： ROBINSON E S & A LTD , KENNETH WILLIAM DAVIES , CLIFFORD LESTER SMITH
IPC分类号： A45D33/00
摘要： 668,076. Powder boxes. ROBINSON, Ltd., E. S. & A., DAVIS, K. W., and SMITH, C. L. Feb. 21, 1949 [Sept. 22, 1948], No. 24817/48. Classes 18 and 66 A powder box with the top, base and side wall formed as a single unit has an aperture in the base closed by a removable transparent disc or lid 7 having an inwardly directed dished portion with an inclined wall to engage the edge of the aperture and an annular flange 9 to rest in a depression 10 in the base. An annular bead 11 is provided on the disc to facilitate its removal. A paper covering 4 is gummed to the top, side wall and part of the base.

7. 发明专利

GB620211A An improved process for the removal of mineral acid from protein hydrolysates 未知
公开(公告)号：GB620211A
公开(公告)日：1949-03-22
申请号：GB67847
申请日：1947-01-08
申请人： GLAXO LAB LTD , ERNEST LESTER SMITH , JAMES ERNEST PAGE
IPC分类号： A23J3/32
摘要： Mineral acids are extracted from protein hydrolysates by treating with an organic base of the formula where R1 is hydrogen or an aliphatic or cycloaliphatic group, and R2 and R3 are aliphatic or cycloaliphatic groups or together form part of a piperidine ring which may contain one or more methyl substituents, the base in all cases containing 12 or more carbon atoms, preferably with tertiary bases containing 16 or more carbon atoms, in an amount equivalent to or in excess of the acid, and separating the relatively insoluble salts produced. Suitable bases are methyldioctyl (or nonyl) amine, trioctylamine, decylpiperidine, triamylamine, n-amyloctylmethylamine, dihexylamine, dinonylamine, and octylcyclohexylamine. Mineral acids comprise strong and weak inorganic acids, e.g. hydrochloric, nitric, sulphuric and phosphoric. Repeated extractions with the bases are generally necessary for removal of weak acids. Solutions of bases in, for example, chloroform, nitrobenzene or light petroleum, may be used, and solvents added during the extraction. In examples, casein, haemoglobin and gelatin are hydrolysed with hydrochloric acid and the solutions extracted with methyldioctylamine in chloroform.

8. 发明专利

GB610731A Improvements in or relating to the purification of penicillin salts 未知
公开(公告)号：GB610731A
公开(公告)日：1948-10-20
申请号：GB420246
申请日：1946-02-11
申请人： GLAXO LAB LTD , ERNEST LESTER SMITH , AUSTIN ERNEST BIDE
IPC分类号： C07D499/00 , C07D499/22
摘要： In an improved process for the preparation of primary amine salts of penicillin, an aqueous solution of a metallic salt of penicillin is treated directly with a salt of a compound of the formula RNH2, where R is a cyclohexyl residue which may contain alkyl substituents containing less than 9 carbon atoms and which compound has a pKH value of not less than 10.2. Preferably, the cooled aqueous solution of the penicillin metallic salt, containing a high concentration of a salting out substance, e.g. sodium chloride, sodium sulphate or potassium chloride, is agitated with a salt of the primary amine causing the primary amine salt of penicillin to separate. Suitable salts of primary amines are those formed with strong mineral acids, specifically such salts of cyclohexylamine and 2-, 3- or 4-methyl cyclohexylamine. In examples: (I) and (III) cyclohexylamine hydrochloride of sodium penicillin react to give cyclohexylamine penicillin, and (II) methyl cyclohexylamine reacts with penicillin to give the methyl cyclohexylamine salt of penicillin. The Provisional Specification includes also the use of additional primary amine salts. Specification 606,482 is referred to.

9. 发明申请

US20170333906A1 SYSTEM AND METHOD FOR MAGNETIC SUSPENSION OF LABORATORY OBJECTS 审中-公开
公开(公告)号：US20170333906A1
公开(公告)日：2017-11-23
申请号：US15397381
申请日：2017-01-03
申请人： Lester Smith Medical Research Institute
发明人： Ramon Coronado , Lauren E. Cornell
IPC分类号： B01L9/02 , F16B1/00 , B01L9/00 , F16M13/02
CPC分类号： F16B1/00 , B01L3/50825 , B01L9/00 , B01L9/02 , B01L9/06 , B01L9/50 , B01L9/52 , B01L2200/141 , B01L2300/16 , F16B11/006 , F16B2001/0035 , F16M13/022 , F16M13/027
摘要： Disclosed is a system and method for aiding the sterility of a laboratory by suspending items using magnetic force to a laboratory object, such as a cap or a lid, wherein such cap may be suspended on a rack or stand comprising an arm extending horizontally. The system allows for suspension of items rather than placing them on surfaces, which may lead to contamination. The system may further prevent mixing of lids by increasing organizational capability by magnetic suspension of the caps or lids. The disclosed system supports a wide variety of scenarios for laboratory settings and related products and services.

10. 发明申请

US20170326105A1 MELATONIN-BASED NASAL COMPOSITIONS AND USES THEREOF 审中-公开
公开(公告)号：US20170326105A1
公开(公告)日：2017-11-16
申请号：US15592005
申请日：2017-05-10
申请人： The Lester Smith Medical Research Institute, LLC
发明人： Ramon Coronado
IPC分类号： A61K31/405 , A61K31/4045 , A61K9/00 , A61K47/40
CPC分类号： A61K31/405 , A61K9/0043 , A61K9/0073 , A61K9/08 , A61K31/4045 , A61K47/10 , A61K47/40 , A61K47/6951 , A61K2300/00
摘要： Disclosed is an improved composition characterized in containing a combination of melatonin and 5-HTP in a nasal administration for the rapid treatment of insomnia, anxiety, and related disorders in mammals, including humans. The present invention relates also to a pharmaceutical composition comprising 5-HTP and melatonin which utilizes the known effects of two substances to provide sleep improvement, relaxation, and reduced anxiety via rapid delivery of the combination, via nasal administration, for short-term alleviation of sleep disorder and anxiety-related symptoms. The combined effects of 5-HTP and melatonin in the present invention provide a short-term increase in blood plasma levels of melatonin while simultaneously increasing the production of serotonin for purposes of achieving natural melatonin biosynthesis in combination with the increased melatonin content in blood plasma.

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