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1. 发明授权

US5929055A Therapeutic method for management of diabetes mellitus 失效
标题翻译：治疗糖尿病的治疗方法
公开(公告)号：US5929055A
公开(公告)日：1999-07-27
申请号：US880945
申请日：1997-06-23
申请人： Maria Emanuel Ryan , Lorne M. Golub , Nungavaram S. Ramamurthy , Thomas F. McNamara
发明人： Maria Emanuel Ryan , Lorne M. Golub , Nungavaram S. Ramamurthy , Thomas F. McNamara
IPC分类号： A61K45/00 , A61K31/155 , A61K31/175 , A61K31/426 , A61K31/65 , A61K38/28 , A61P3/10
CPC分类号： A61K38/28 , Y10S514/866
摘要： A method for treating diabetes in a mammal by moderately controlling blood glucose concentration in the mammal together with administering to the mammal an amount of a tetracycline compound effective to reduce complications associated with diabetic hyperglycemia. The method enables long term management of diabetes by avoiding the problems associated with tight control of blood glucose concentrations, i.e., hypoglycemia tolerance and seizures, while simultaneously avoiding the problems associated with conventional moderate control of blood glucose concentrations, i.e., pathological complications associated with hyperglycemia, such as nephropathy, retinopathy, etc. Blood glucose concentration can be controlled by moderate administration (e.g., fewer injections per day) of insulin or another glucose-modulating agent, while pathological complications characteristic of diabetic hyperglycemia are ameliorated through the activity of tetracycline compound, the latter preferably administered in an amount that is substantially non-antimicrobial.
摘要翻译：一种通过适度控制哺乳动物中的血糖浓度来治疗哺乳动物的糖尿病的方法，同时向哺乳动物施用一定量的有效减少与糖尿病性高血糖相关并发症的四环素化合物。该方法能够通过避免与血糖浓度的严格控制（即低血糖耐受和癫痫发作）相关的问题，同时避免与常规的中度控制血糖浓度相关的问题，即与高血糖相关的病理性并发症，如肾病，视网膜病变等。血糖浓度可以通过中度给药（例如，每天更少的注射）胰岛素或另一种葡萄糖调节剂来控制，而通过四环素化合物的活性来改善糖尿病性高血糖症状的病理并发症，后者优选以基本上非抗微生物的量施用。

2. 发明授权

US5827840A Promotion of wound healing by chemically-modified tetracyclines 失效
标题翻译：通过化学改性的四环素促进伤口愈合
公开(公告)号：US5827840A
公开(公告)日：1998-10-27
申请号：US691135
申请日：1996-08-01
申请人： Nungavaram S. Ramamurthy , Lorne M. Golub , Thomas F. McNamara
发明人： Nungavaram S. Ramamurthy , Lorne M. Golub , Thomas F. McNamara
IPC分类号： A61K31/65 , A61K45/06 , A61L15/44 , A61P17/02
CPC分类号： A61L15/44 , A61K31/65 , A61K45/06 , A61L2300/406 , A61L2300/41 , A61L2300/412
摘要： A method for improving the healing response of epithelialized tissue (e.g., skin, mucosae) to acute traumatic injury is disclosed. The method includes employing a tetracycline compound, having substantially no antibacterial activity, to improve the capacity of the epithelialized tissue to heal acute wounds. Specifically, the method involves increasing the rate of collagen accumulation of the healing epithelialized tissue above that associated with wound healing in the individual. The method decreases proteolytic activity in the epithelialized tissue by means of the tetracycline compound, most commonly decreasing collagenolytic activity and/or decreasing gelatinolytic activity. Collagenase and gelatinase activity have been shown to be decreased by the method of the invention. Preferably, the method is employed to improve the wound healing capacity of human or animal subjects in whom such capacity is impaired. Also, the non-antibiotic tetracycline is preferably administered topically at the site of the wound.
摘要翻译：公开了一种改善上皮组织（例如皮肤，粘膜）对急性创伤性损伤的愈合反应的方法。该方法包括使用基本上没有抗菌活性的四环素化合物，以改善上皮组织治愈急性创伤的能力。具体地说，该方法包括增加愈合上皮组织的胶原蛋白积累速率高于个体伤口愈合以上。该方法通过四环素化合物降低上皮组织中的蛋白水解活性，最常降低胶原分解活性和/或降低明胶溶解活性。通过本发明的方法已显示胶原酶和明胶酶活性降低。优选地，该方法用于改善受损的人或动物受试者的伤口愈合能力。此外，非抗生素四环素优选在伤口部位局部施用。

3. 发明授权

US4704383A Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same 失效
公开(公告)号：US4704383A
公开(公告)日：1987-11-03
申请号：US699048
申请日：1985-02-07
申请人： Thomas F. McNamara , Nungavaram S. Ramamurthy , Lorne M. Golub
发明人： Thomas F. McNamara , Nungavaram S. Ramamurthy , Lorne M. Golub
IPC分类号： A23K1/165 , A23K1/16 , A23K1/17 , A61K31/65 , A61P1/02 , A61P3/00 , A61P43/00
CPC分类号： A61K31/65
摘要： Tetracyclines having substantially no effective antibiotic or antibacterial activity and possessing anti-collagen-destructive enzyme activity or anti-collagenase activity and compositions containing the same have been found useful as anti-collagenolytic agents. Such tetracyclines and compositions containing the same are useful in the treatment of periodontal diseases, corneal ulcers, bone deficiency disorders, rheumatoid arthritis diseases characterized by excessive collagen destruction. A special aspect of this invention involves the incorporation of such tetracyclines in animal feed compositions for improved animal nutrition, such as may be evidenced by increased weight gain.

4. 发明授权

US4935411A Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same 失效
公开(公告)号：US4935411A
公开(公告)日：1990-06-19
申请号：US117376
申请日：1987-10-28
申请人： Thomas F. McNamara , Nungavaram S. Ramamurthy , Lorne M. Golub
发明人： Thomas F. McNamara , Nungavaram S. Ramamurthy , Lorne M. Golub
IPC分类号： A61K31/65
CPC分类号： A61K31/65
摘要： Tetracyclines having substantially no effective antibiotic or antibacterial activity and possessing anti-collagen-destructive enzyme activity or anti-collagenase activity and compositions containing the same have been found useful as anti-collagenolytic agents. Such tetracyclines and compositions containing the same are useful in the treatment of periodontal diseases, corneal ulcers, bone deficiency disorders, rheumatoid arthritis diseases characterized by excessive collagen destruction. A special aspect of this invention involves the incorporation of such tetracyclines in animal feed compositions for improved animal nutrition, such as may be evidenced by increased weight gain.

5. 发明授权

US4925833A Use of tetracycline to enhance bone protein synthesis and/or treatment of osteoporosis 失效
标题翻译：使用四环素来增强骨蛋白合成和/或治疗骨质疏松症
公开(公告)号：US4925833A
公开(公告)日：1990-05-15
申请号：US946726
申请日：1986-12-29
申请人： Thomas F. McNamara , Lorne M. Golub , Nungavaram S. Ramamurthy
发明人： Thomas F. McNamara , Lorne M. Golub , Nungavaram S. Ramamurthy
IPC分类号： A61K31/65
CPC分类号： A61K31/65
摘要： Tetracyclines, antibacterial and non-antibacterial tetracyclines, have been found to be useful in the treatment of osteoporosis in humans by administering to the human suffering from osteoporosis an effective amount of a tetracycline to enhance bone protein synthesis. Tetracyclines which have been found to be effective in the treatment of osteoporosis in humans include minocycline, doxycycline and dedimethylaminotetracyline.
摘要翻译：已经发现四环素类抗生素和非抗菌四环素通过对患有骨质疏松症的人施用有效量的四环素来增强骨蛋白质合成，可用于治疗人类的骨质疏松症。已发现在人类骨质疏松症治疗中有效的四环素包括米诺环素，多西环素和去二甲基氨基四环素。

6. 发明授权

US06429204B1 Method of inhibiting cancer growth 有权
标题翻译：抑制癌症生长的方法
公开(公告)号：US06429204B1
公开(公告)日：2002-08-06
申请号：US09542402
申请日：2000-04-03
申请人： Lorne M. Golub , Thomas F. McNamara , Nungavaram S. Ramamurthy , Hsi-Ming Lee , Sanford Simon , Balakrishna L. Lokeshwar , Marie G. Selzer , Norman L. Block
发明人： Lorne M. Golub , Thomas F. McNamara , Nungavaram S. Ramamurthy , Hsi-Ming Lee , Sanford Simon , Balakrishna L. Lokeshwar , Marie G. Selzer , Norman L. Block
IPC分类号： A61K3165
CPC分类号： A61K31/65 , A61K31/00
摘要： The invention is a method of inhibiting a sarcoma, such as Kaposi's sarcoma, in a mammal. The method employs 6-demethyl-6-deoxy-4-de(dimethylamino)tetracycline (CMT-3.)
摘要翻译：本发明是哺乳动物抑制肉瘤如卡波西肉瘤的方法。该方法采用6-脱甲基-6-脱氧-4-脱（二甲氨基）四环素（CMT-3）

7. 发明授权

US6100248A Method of inhibiting cancer growth 失效
标题翻译：抑制癌症生长的方法
公开(公告)号：US6100248A
公开(公告)日：2000-08-08
申请号：US7645
申请日：1998-01-15
申请人： Lorne M. Golub , Thomas F. McNamara , Nungavaram S. Ramamurthy , Hsi-Ming Lee , Sanford Simon , Balakrishna L. Lokeshwar , Marie G. Selzer , Norman L. Block
发明人： Lorne M. Golub , Thomas F. McNamara , Nungavaram S. Ramamurthy , Hsi-Ming Lee , Sanford Simon , Balakrishna L. Lokeshwar , Marie G. Selzer , Norman L. Block
IPC分类号： A61K31/00 , A61K31/65 , A61P35/00 , A01N37/18
CPC分类号： A61K31/65 , A61K31/00
摘要： The invention is a method of inhibiting cancer growth, by inhibiting cellular proliferation, invasiveness, or metastasis, or by inducing cytotoxicity against cancer in mammals. The method employs 6-demethyl-6-deoxy-4-de(dimethylamino)tetracycline (CMT-3) and other functionally related chemically modified, preferably non-antibacterial, tetracycline compounds to inhibit cancer growth. The method is particularly effective to inhibit the establishment, growth, and metastasis of solid tumors, such as tumors derived from colon cancer cells, breast cancer cells, melanoma cells, prostatic carcinoma cells, or lung cancer cells.
摘要翻译：本发明是通过抑制细胞增殖，侵袭或转移，或通过诱导哺乳动物对癌症的细胞毒性来抑制癌症生长的方法。该方法采用6-脱甲基-6-脱氧-4-脱（二甲基氨基）四环素（CMT-3）和其他功能相关的化学修饰，优选非抗菌四环素化合物以抑制癌症生长。该方法特别有效地抑制了实体瘤如来自结肠癌细胞，乳腺癌细胞，黑素瘤细胞，前列腺癌细胞或肺癌细胞的肿瘤的建立，生长和转移。

8. 发明授权

US5919775A Method for inhibiting expression of inducible nitric oxide synthase with tetracycline 失效
标题翻译：用四环素抑制诱导型一氧化氮合酶表达的方法
公开(公告)号：US5919775A
公开(公告)日：1999-07-06
申请号：US61286
申请日：1998-04-16
申请人： Ashok R. Amin , Steven B. Abramson , Lorne M. Golub , Nungavaram S. Ramamurthy , Thomas F. McNamara , Robert A. Greenwald , Howard Trachtman
发明人： Ashok R. Amin , Steven B. Abramson , Lorne M. Golub , Nungavaram S. Ramamurthy , Thomas F. McNamara , Robert A. Greenwald , Howard Trachtman
IPC分类号： A61K31/65 , A61P13/12 , A61P19/02 , A61P29/00 , A61P43/00
CPC分类号： A61K31/65
摘要： The invention is a method of inhibiting the production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo biological system. The method employs a tetracycline compound to inhibit the production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the biological system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.
摘要翻译：本发明是一种在体内，体外或离体生物体系中抑制一氧化氮（NO）的产生的方法。该方法采用四环素化合物抑制NO的产生和/或抑制一氧化氮合酶（iNOS）的诱导型异构体的表达或活性。优选地，四环素化合物对金属蛋白酶具有抑制活性。此外，优选的是，四环素化合物以系统中几乎没有或没有抗菌活性的量提供给生物系统。因此，优选的四环素化合物是四环素化合物，其被修饰以降低或消除其抗微生物活性。该方法可用于治疗以iNOS介导的NO产生为特征的哺乳动物的医疗状况，包括例如炎性病症。

9. 发明授权

US5837696A Method of inhibiting cancer growth 失效
标题翻译：抑制癌症生长的方法
公开(公告)号：US5837696A
公开(公告)日：1998-11-17
申请号：US783655
申请日：1997-01-15
申请人： Lorne M. Golub , Thomas F. McNamara , Nungavaram S. Ramamurthy , Hsi-Ming Lee , Sanford Simon , Balakrishna L. Lokeshwar , Marie G. Selzer , Norman L. Block
发明人： Lorne M. Golub , Thomas F. McNamara , Nungavaram S. Ramamurthy , Hsi-Ming Lee , Sanford Simon , Balakrishna L. Lokeshwar , Marie G. Selzer , Norman L. Block
IPC分类号： A61K31/00 , A61K31/65 , A61P35/00 , A01N37/18
CPC分类号： A61K31/65 , A61K31/00
摘要： The invention is a method of inhibiting cancer growth, including cellular proliferation, invasiveness, or metastasis in mammals. The method employs 6-demethyl-6-deoxy-4-dedimethylaminotetracycline (CMT-3) and other functionally related chemically modified, preferably non-antibacterial, tetracycline compounds to inhibit cancer growth. The method is particularly effective to inhibit the establishment, growth, and metastasis of solid tumors, such as tumors derived from colon cancer cells, breast cancer cells, melanoma cells, prostatic carcinoma cells, or lung cancer cells.
摘要翻译：本发明是抑制哺乳动物癌细胞增殖，包括细胞增殖，侵袭或转移的方法。该方法采用6-脱甲基-6-脱氧-4-脱二甲基氨基四环素（CMT-3）和其他功能相关的化学修饰的，优选非抗菌的四环素化合物以抑制癌症生长。该方法特别有效地抑制了实体瘤如来自结肠癌细胞，乳腺癌细胞，黑素瘤细胞，前列腺癌细胞或肺癌细胞的肿瘤的建立，生长和转移。

10. 发明授权

US5789395A Method of using tetracycline compounds for inhibition of endogenous nitric oxide production 失效
标题翻译：使用四环素化合物抑制内源性一氧化氮产生的方法
公开(公告)号：US5789395A
公开(公告)日：1998-08-04
申请号：US697815
申请日：1996-08-30
申请人： Ashok R. Amin , Steven B. Abramson , Lorne M. Golub , Nungavaram S. Ramamurthy , Thomas F. McNamara , Robert A. Greenwald , Howard Trachtman
发明人： Ashok R. Amin , Steven B. Abramson , Lorne M. Golub , Nungavaram S. Ramamurthy , Thomas F. McNamara , Robert A. Greenwald , Howard Trachtman
IPC分类号： A61K31/65 , A61P13/12 , A61P19/02 , A61P29/00 , A61P43/00 , C12N9/99 , C12N9/04 , C12N9/06
CPC分类号： A61K31/65
摘要： A method is disclosed for inhibiting endogenous production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo mammalian system. The method employs a tetracycline compound to inhibit production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the mammalian system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.
摘要翻译：公开了用于抑制体内，体外或离体哺乳动物系统中一氧化氮（NO）的内源性产生的方法。该方法采用四环素化合物抑制NO的产生和/或抑制一氧化氮合酶（iNOS）的诱导型亚型的表达或活性。优选地，四环素化合物对金属蛋白酶具有抑制活性。此外，优选的是，四系环化合物以系统中几乎没有或没有抗菌活性的量提供给哺乳动物系统。因此，优选的四环素化合物是四环素化合物，其被修饰以降低或消除其抗微生物活性。该方法可用于治疗以iNOS介导的NO产生为特征的哺乳动物的医疗状况，包括例如炎性病症。

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