公开(公告)号：US20060093670A1

公开(公告)日：2006-05-04

申请号：US10516122

申请日：2003-06-09

申请人： Yutaka Mizushima ,  Yukie Takagi ,  Tomomi Hagi ,  Toshiyuki Ikoma

发明人： Yutaka Mizushima ,  Yukie Takagi ,  Tomomi Hagi ,  Toshiyuki Ikoma

IPC分类号： A61K38/39 ,  A61K31/737 ,  A61K9/22

CPC分类号： A61K9/0024 ,  A61K9/143 ,  A61K9/1611

摘要： The present invention provides a sustained-release composition by which a sustained-release effect can be obtained for a long time when injecting microparticles of the composition in an amount that can be subcutaneously or intramuscularly injected to a human with ease and without pain. The composition comprises porous hydroxyapatite microparticles having pores embolized by filling the pores in the microparticles with a biologically active drug, a human serum protein, and a mucopolysaccharide, and adding a divalent metal ion. Alternatively, the composition comprises porous hydroxyapatite microparticles having pores embolized in the outer layer by filling the pores in the microparticles with a biologically active drug, a human serum protein, and a water-soluble calcium salt one after another or at one time, and then adding sodium carbonate, sodium hydrogen carbonate, or an aqueous carbonate ion solution.

摘要翻译： 本发明提供了一种持续释放组合物，通过该缓释组合物，将组合物的微粒注入可以皮下或肌肉内注射的人容易且无疼痛的长时间下，可以获得持续释放作用。 该组合物包含通过用生物活性药物，人血清蛋白质和粘多糖填充微粒中的孔而堵塞孔的多孔羟基磷灰石微粒，并加入二价金属离子。 或者，组合物包含多孔羟基磷灰石微粒，其通过用生物活性药物，人血清蛋白和水溶性钙盐一次又一次或一次填充微粒中的孔，在外层中堵塞孔，然后 加入碳酸钠，碳酸氢钠或碳酸氢钠水溶液。

公开(公告)号：US08313767B2

公开(公告)日：2012-11-20

申请号：US12837810

申请日：2010-09-02

申请人： Yutaka Mizushima ,  Yasuaki Ogawa ,  Junzo Tanaka ,  Toshiyuki Ikoma

发明人： Yutaka Mizushima ,  Yasuaki Ogawa ,  Junzo Tanaka ,  Toshiyuki Ikoma

IPC分类号： A61K9/22 ,  A61K9/14 ,  A61K33/30 ,  A61K38/00 ,  A61K31/70 ,  A61K31/7088 ,  A61K31/56 ,  A61K31/315

CPC分类号： A61K31/00 ,  A61K9/1611 ,  A61K33/30 ,  A61K33/42 ,  A61K45/06 ,  A61K2300/00

摘要： Sustained release microparticles suitable for various types of drugs, or drug-containing sustained release microparticles capable of sustained release of drugs over a period of three days or more and capable of inhibiting initial burst release; a process for producing the same; and preparations containing the microparticles are disclosed. The drug-containing sustained release microparticles comprise a drug other than human growth hormone and a porous apatite derivative, and optionally include a water-soluble bivalent metal compound. The drug-containing sustained release microparticles can be produced by dispersing under agitation microparticles of a porous apatite derivative in an aqueous solution containing a drug so that the aqueous solution infiltrates into the porous apatite derivative; optionally adding an aqueous solution containing a water-soluble bivalent metal compound that may infiltrate into the porous apatite derivative; further adding additives such as a stabilizer to the mixture; and effecting lyophilization or vacuum drying.

摘要翻译： 适用于各种类型药物的持续释放微粒，或能够在三天或更长时间内持续释放药物并且能够抑制初始爆发释放的药物持续释放微粒; 其制造方法; 并且公开了含有微粒的制剂。 含药物的缓释微粒包含除人生长激素以外的药物和多孔磷灰石衍生物，任选地包含水溶性二价金属化合物。 含药缓释微粒可以通过将多孔磷灰石衍生物的微粒分散在含有药物的水溶液中分散而制成，使得水溶液渗透到多孔磷灰石衍生物中; 任选地加入含有可渗透到多孔磷灰石衍生物中的水溶性二价金属化合物的水溶液; 进一步向混合物中加入稳定剂等添加剂; 并进行冻干或真空干燥。

公开(公告)号：US20060153930A1

公开(公告)日：2006-07-13

申请号：US10559512

申请日：2004-06-11

申请人： Yutaka Mizushima ,  Yasuaki Ogawa ,  Junzo Tanaka ,  Toshiyuki Ikoma

发明人： Yutaka Mizushima ,  Yasuaki Ogawa ,  Junzo Tanaka ,  Toshiyuki Ikoma

IPC分类号： A61K33/42

CPC分类号： A61K31/00 ,  A61K9/1611 ,  A61K33/30 ,  A61K33/42 ,  A61K45/06 ,  A61K2300/00

摘要： Sustained release microparticles suitable for various types of drugs, or drug-containing sustained release microparticles capable of sustained release of drugs over a period of three days or more and capable of inhibiting initial burst release; a process for producing the same; and preparations containing the microparticles are disclosed. The drug-containing sustained release microparticles comprise a drug other than human growth hormone and a porous apatite derivative, and optionally include a water-soluble bivalent metal compound. The drug-containing sustained release microparticles can be produced by dispersing under agitation microparticles of a porous apatite derivative in an aqueous solution containing a drug so that the aqueous solution infiltrates into the porous apatite derivative; optionally adding an aqueous solution containing a water-soluble bivalent metal compound that may infiltrate into the porous apatite derivative; further adding additives such as a stabilizer to the mixture; and effecting lyophilization or vacuum drying.

摘要翻译： 适用于各种类型药物的持续释放微粒，或能够在三天或更长时间内持续释放药物并且能够抑制初始爆发释放的药物持续释放微粒; 其制造方法; 并且公开了含有微粒的制剂。 含药物的缓释微粒包含除人生长激素以外的药物和多孔磷灰石衍生物，任选地包含水溶性二价金属化合物。 含药缓释微粒可以通过将多孔磷灰石衍生物的微粒分散在含有药物的水溶液中分散而制成，使得水溶液渗透到多孔磷灰石衍生物中; 任选地加入含有可渗透到多孔磷灰石衍生物中的水溶性二价金属化合物的水溶液; 进一步向混合物中加入稳定剂等添加剂; 并进行冻干或真空干燥。

公开(公告)号：US20100322902A1

公开(公告)日：2010-12-23

申请号：US12837810

申请日：2010-09-02

申请人： Yutaka Mizushima ,  Yasuaki Ogawa ,  Junzo Tanaka ,  Toshiyuki Ikoma

发明人： Yutaka Mizushima ,  Yasuaki Ogawa ,  Junzo Tanaka ,  Toshiyuki Ikoma

IPC分类号： A61K38/21 ,  A61K47/02 ,  A61K31/573

CPC分类号： A61K31/00 ,  A61K9/1611 ,  A61K33/30 ,  A61K33/42 ,  A61K45/06 ,  A61K2300/00

摘要： Sustained release microparticles suitable for various types of drugs, or drug-containing sustained release microparticles capable of sustained release of drugs over a period of three days or more and capable of inhibiting initial burst release; a process for producing the same; and preparations containing the microparticles are disclosed. The drug-containing sustained release microparticles comprise a drug other than human growth hormone and a porous apatite derivative, and optionally include a water-soluble bivalent metal compound. The drug-containing sustained release microparticles can be produced by dispersing under agitation microparticles of a porous apatite derivative in an aqueous solution containing a drug so that the aqueous solution infiltrates into the porous apatite derivative; optionally adding an aqueous solution containing a water-soluble bivalent metal compound that may infiltrate into the porous apatite derivative; further adding additives such as a stabilizer to the mixture; and effecting lyophilization or vacuum drying.

摘要翻译： 适用于各种类型药物的持续释放微粒，或能够在三天或更长时间内持续释放药物并且能够抑制初始爆发释放的药物持续释放微粒; 其制造方法; 并且公开了含有微粒的制剂。 含药物的缓释微粒包含除人生长激素以外的药物和多孔磷灰石衍生物，任选地包含水溶性二价金属化合物。 含药缓释微粒可以通过将多孔磷灰石衍生物的微粒分散在含有药物的水溶液中分散而制成，使得水溶液渗透到多孔磷灰石衍生物中; 任选地加入含有可渗透到多孔磷灰石衍生物中的水溶性二价金属化合物的水溶液; 进一步向混合物中加入稳定剂等添加剂; 并进行冻干或真空干燥。

公开(公告)号：US20100143321A1

公开(公告)日：2010-06-10

申请号：US12519437

申请日：2007-12-19

申请人： Kouji Shirai ,  Tatsuo Kawashima ,  Toshihisa Kuroda ,  Yutaka Mizushima ,  Ayako Mizushima ,  Masahiro Murakami ,  Tomoharu Fukuzaki

发明人： Kouji Shirai ,  Tatsuo Kawashima ,  Toshihisa Kuroda ,  Yutaka Mizushima ,  Ayako Mizushima ,  Masahiro Murakami ,  Tomoharu Fukuzaki

IPC分类号： A61K38/44 ,  A61P11/00

CPC分类号： A61K31/573 ,  A61K9/0019 ,  A61K38/00 ,  A61K47/26 ,  A61K47/544 ,  C12N9/0089

摘要： A therapeutic agent for interstitial pneumonia is provided which effectively exploits the effect of superoxide dismutase (SOD). The therapeutic composition for interstitial pneumonia contains 10 to 100 mg of lecithinized superoxide dismutase represented by the following general formula (I): SOD′(Q-B)m   (I) (wherein SOD′ is a residue of superoxide dismutase; Q is a chemical crosslink; B is a residue of lysolecithin having the hydrogen atom of the hydroxyl group at position 2 of its glycerol moiety removed; and m is the average number of lysolecithin molecules bound to one molecule of the superoxide dismutase and is an integer of 1 or greater) and further contains sucrose to give it a stable form suitable for intravenous administration.

摘要翻译： 提供间质性肺炎治疗剂，有效利用超氧化物歧化酶（SOD）的作用。 间质性肺炎的治疗组合物含有10-100mg由以下通式（I）表示的卵磷脂化超氧化物歧化酶：SOD'（QB）m（I）（其中SOD'是超氧化物歧化酶的残基; Q是化学交联 ; B是除去其甘油部分的位置2处的羟基的氢原子的溶血卵磷脂的残基; m是与1分子超氧化物歧化酶结合的溶血卵磷脂分子的平均数，为1以上的整数） 并且还含有蔗糖以使其具有适于静脉内施用的稳定形式。

公开(公告)号：US20100129456A1

公开(公告)日：2010-05-27

申请号：US12597969

申请日：2008-04-11

申请人： Tsutomu Ishihara ,  Yutaka Mizushima ,  Ayako Mizushima ,  Toru Mizushima

发明人： Tsutomu Ishihara ,  Yutaka Mizushima ,  Ayako Mizushima ,  Toru Mizushima

IPC分类号： A61K9/14

CPC分类号： A61K9/5153 ,  A61K9/19 ,  A61K9/5192 ,  A61K31/00 ,  A61K45/06

摘要： A nanoparticle containing a low-molecular-weight drug having a negatively charged group is provided that is effectively targeted to an affected site, is capable of sufficiently sustained release of the drug, and has a reduced tendency to accumulate in the liver to cause reduced side effects. The nanoparticle containing a low-molecular-weight drug having a negatively charged group is obtained by hydrophobicizing the low-molecular-weight drug having a negatively charged group with a metal ion, and reacting the hydrophobicized drug with poly L-lactic acid or poly(L-lactic acid/glycolic acid) copolymer and poly DL- or L-lactic acid-polyethylene glycol block copolymer or poly(DL- or L-lactic acid/glycolic acid)-polyethylene glycol block copolymer.

摘要翻译： 提供了含有具有带负电荷的基团的低分子量药物的纳米粒子，其有效靶向受影响部位，能够充分持续释放药物，并且具有减少的积聚在肝脏中的趋势，导致减少的侧面 效果。 含有带负电荷基团的低分子量药物的纳米粒子是通过用金属离子疏水化具有带负电荷的基团的低分子量药物，并使疏水化药物与聚-L-乳酸或聚（ L-乳酸/乙醇酸）共聚物和聚DL-或L-乳酸 - 聚乙二醇嵌段共聚物或聚（DL-或L-乳酸/乙醇酸） - 聚乙二醇嵌段共聚物。

公开(公告)号：US07642230B2

公开(公告)日：2010-01-05

申请号：US10555191

申请日：2004-04-01

申请人： Michio Kimura ,  Tomoko Eto ,  Yutaka Mizushima

发明人： Michio Kimura ,  Tomoko Eto ,  Yutaka Mizushima

IPC分类号： A61K38/02 ,  A61K33/30 ,  A61K33/42

CPC分类号： C07K16/241 ,  A61K9/0019 ,  A61K9/10 ,  A61K33/30 ,  A61K38/193 ,  A61K38/212 ,  A61K38/27 ,  A61K45/06 ,  A61K47/02 ,  A61K2300/00

摘要： With a simple and high-yield production method, a zinc-containing sustained-release composition capable of stabilizing a physiologically active protein or peptide, typically G-CSF by precipitation and retaining drug efficacy for several days in a living body owing to its sustained releasability is provided. Concretely, a zinc-containing sustained-release composition produced by forming a precipitate by mixing a physiologically active protein or peptide, a water-soluble zinc salt, a water-soluble carbonate and/or a water soluble phosphate aqueous solution. The zinc-containing sustained-release composition may be administered as a zinc-containing sustained preparation by adding a pharmaceutically acceptable additive as is necessary.

摘要翻译： 通过简单且高产量的生产方法，能够通过沉淀稳定生理活性蛋白质或肽，通常为G-CSF的锌含量缓释组合物，由于其具有持续的释放性，在活体中保持药物疗效几天 被提供。 具体地说，通过混合生理活性蛋白质或肽，水溶性锌盐，水溶性碳酸盐和/或水溶性磷酸盐水溶液形成沉淀物而制备的含锌缓释组合物。 含锌持续释放组合物可以通过根据需要添加药学上可接受的添加剂作为含锌缓释制剂施用。

公开(公告)号：US20080113014A1

公开(公告)日：2008-05-15

申请号：US10597483

申请日：2004-12-15

申请人： Toru Mizushima ,  Yutaka Mizushima

发明人： Toru Mizushima ,  Yutaka Mizushima

IPC分类号： A61K9/127 ,  G01N33/92 ,  A61K31/192 ,  A61K31/60 ,  A61K31/56

CPC分类号： G01N33/5076 ,  G01N33/5008 ,  G01N33/5014 ,  G01N33/5432 ,  G01N33/582 ,  G01N33/586 ,  G01N2500/00

摘要： A method for screening for compounds or salts thereof, in particular nonsteroidal anti-inflammatory compounds or salts thereof, that are safe for gastric mucosa and cause little gastrointestinal side effects. The method uses a particular liposome to serve as a cell membrane model. The liposome encapsulates a fluorescent dye, in particular, calcein and is formed of phospholipids, such as phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, and phosphatidylinositol. A test compound is allowed to react with the liposome and the leakage of the fluorescent dye from the liposome is evaluated. As a result, compounds safe for gastric mucosa, in particular, anti-inflammatory compounds can be screened.

摘要翻译： 用于筛选其对胃粘膜安全并且引起很少胃肠道副作用的化合物或其盐，特别是非甾体抗炎化合物或其盐的方法。 该方法使用特定的脂质体作为细胞膜模型。 脂质体封装荧光染料，特别是钙黄绿素，并由磷脂形成，例如磷脂酰胆碱，磷脂酰甘油，磷脂酰丝氨酸和磷脂酰肌醇。 使测试化合物与脂质体反应，并评估荧光染料从脂质体的泄漏。 因此，可以筛选对胃粘膜，特别是抗炎化合物安全的化合物。

公开(公告)号：US5120870A

公开(公告)日：1992-06-09

申请号：US597870

申请日：1990-10-12

申请人： Yutaka Mizushima ,  Toshihide Inomata ,  Arata Yasuda

发明人： Yutaka Mizushima ,  Toshihide Inomata ,  Arata Yasuda

IPC分类号： A61K9/107 ,  A61K31/557 ,  A61K31/5575 ,  A61P43/00 ,  C07C69/732 ,  C07C405/00

CPC分类号： C07C405/00 ,  A61K31/557 ,  A61K9/1075 ,  B82Y5/00 ,  C07C69/732 ,  Y02P20/55

摘要： An emulsion of lipid containing a prostaglandin analogue of the formula (1): ##STR1## wherein R.sup.1 is an alkanoyl group, R.sup.2 is a hydrogen atom or an alkyl group, each of R.sup.3 and R.sup.4 is a hydrogen atom or a protective group for an alcohol, R.sup.5 is an alkyl group which may have a substituent, and is a single bond or a double bond.

公开(公告)号：US20090317479A1

公开(公告)日：2009-12-24

申请号：US12159023

申请日：2006-11-29

申请人： Tsutomu Ishihara ,  Yutaka Mizushima ,  Ayoko Mizushima

发明人： Tsutomu Ishihara ,  Yutaka Mizushima ,  Ayoko Mizushima

IPC分类号： A61K9/14 ,  A61K31/57 ,  A61K31/19 ,  A61P29/00 ,  A61P35/00 ,  A61P31/00

CPC分类号： A61K9/5153 ,  A61K9/0019 ,  A61K9/0024 ,  A61K9/19 ,  A61K9/5192 ,  A61K31/5575 ,  A61K31/56 ,  A61K33/24 ,  A61K33/26 ,  A61K33/30 ,  A61K33/32 ,  A61K33/34 ,  A61K45/06 ,  A61K47/34 ,  A61K47/38

摘要： Drug-containing nanoparticles are provided that enable effective targeting and sustained-release of a water-soluble, non-peptide, low-molecular weight drug and cause reduced accumulation of the drug in the liver. The nanoparticles containing a water-soluble, non-peptide, low-molecular weight drug are obtained by hydrophobicizing the water-soluble, non-peptide, low-molecular weight drug by a metal ion, and reacting the hydrophobicized drug with a poly(lactic acid)-polyethylene glycol block copolymer or a poly(lactic-co-glycolic acid)-polyethylene glycol block copolymer. The nanoparticles have favorable targeting and sustained-release properties and cause reduced accumulation of the drug in the liver.

摘要翻译： 提供含有药物的纳米颗粒，其能够有效靶向和持续释放水溶性，非肽，低分子量药物，并导致药物在肝脏中的积累减少。 含有水溶性非肽低分子量药物的纳米颗粒是通过金属离子疏水化水溶性非肽低分子量药物，并将疏水化药物与聚（乳酸 酸） - 聚乙二醇嵌段共聚物或聚（乳酸 - 共 - 乙醇酸） - 聚乙二醇嵌段共聚物。 纳米颗粒具有有利的靶向和持续释放性质，并且导致药物在肝脏中的积累减少。