公开(公告)号：US20050123484A1

公开(公告)日：2005-06-09

申请号：US10956819

申请日：2004-10-01

申请人： Jane Hirsh ,  Donald Tibbetts ,  Mark Hirsh

发明人： Jane Hirsh ,  Donald Tibbetts ,  Mark Hirsh

IPC分类号： A61K9/12 ,  A61K31/00 ,  A61K31/24 ,  A61K31/245 ,  A61K45/06 ,  A61P23/02 ,  A61L9/04

CPC分类号： A61K31/245 ,  A61K9/12 ,  A61K31/00 ,  A61K31/24 ,  A61K45/06 ,  A61K2300/00

摘要： A topical liquid aerosol formulation for accurate metered dose delivery has been developed which includes a concentrate comprising a local anesthetic in a non-alcohol solvent and a hydrofluorocarbon (HFC) propellant. In the preferred embodiment, the concentration of the non-alcohol solvent in the concentrate is between about 75% and 85% by weight of the formulation. In the most preferred embodiment, the non-alcohol solvent is a water-soluble polyol such as ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, oligoalkylene glycols, liquid polyalkylene glycols, or combinations thereof. In one embodiment, the concentration of the local anesthetic in the concentrate is between about 15% and 25% by weight. In the preferred embodiment, the hydrofluorocarbon propellant is 1,1,1,2-tetrafluoroethane 1,1,1,2,3,3,3-heptafluoropropane or combinations thereof, in a concentration between about 35% and 65% by weight of the final formulation, more preferably between about 45% and 55% by weight of the final formulation. A particularly preferred formulation includes benzocaine, tetracaine, and butylaminobenzoate, wherein the concentration of benzocaine in the concentrate is 14% by weight, the concentration of tetracaine in the concentrate is 2% by weight, and the concentration of butylaminobenzoate in the concentrate is 2% by weight. It has been found that the formulation is more stable in the substantial absence of oxygen. The formulation is preferably administered using a metered dose device for release of a controlled amount of the local anesthetic.

摘要翻译： 已经开发了用于精确计量剂量递送的局部液体气溶胶制剂，其包括在非醇溶剂中的局部麻醉剂和氢氟烃（HFC）推进剂的浓缩物。 在优选的实施方案中，浓缩物中非醇溶剂的浓度为制剂重量的约75％至85％。 在最优选的实施方案中，非醇溶剂是水溶性多元醇，例如乙二醇，丙二醇，甘油，二甘醇，二丙二醇，低聚亚烷基二醇，液体聚亚烷基二醇或其组合。 在一个实施方案中，浓缩物中局部麻醉剂的浓度为约15重量％至25重量％。 在优选的实施方案中，氢氟烃推进剂是1,1,1,2-四氟乙烷1,1,1,2,3,3,3-七氟丙烷或其组合，其浓度为约35-65重量％ 最终制剂，更优选为最终制剂重量的约45％至55％。 特别优选的制剂包括苯佐卡因，丁卡因和丁基氨基苯甲酸酯，其中浓缩物中苯佐卡因的浓度为14重量％，浓缩物中丁卡因的浓度为2重量％，浓缩物中丁基氨基苯甲酸酯的浓度为2重量％ 重量。 已经发现，在基本不存在氧的情况下，制剂更加稳定。 制剂优选使用计量剂量装置施用以释放受控量的局部麻醉剂。

公开(公告)号：US20050255048A1

公开(公告)日：2005-11-17

申请号：US11128947

申请日：2005-05-13

申请人： Mark Hirsh ,  Jane Hirsh ,  Ira Skolnik ,  Mark Trumbore

发明人： Mark Hirsh ,  Jane Hirsh ,  Ira Skolnik ,  Mark Trumbore

IPC分类号： A61K9/12 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/496 ,  A61K31/58 ,  A61K31/65 ,  A61K31/704 ,  A61K31/7048

CPC分类号： A61K31/58 ,  A61K9/0014 ,  A61K9/06 ,  A61K9/122 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/496 ,  A61K31/65 ,  A61K31/704 ,  A61K31/7048 ,  A61K45/06 ,  A61K2300/00

摘要： A topical spray or foam, methods of making the formulation, and methods of use thereof, has been developed. In one preferred embodiment, the composition includes one or more active agents and exhibits both antibacterial activity and antifungal activity. Excipients such as chemical disinfectants, anti-pruritic agents to minimize itching, and skin protective compounds may be added. The composition may be formulated to be dispensed as a spray or foam and the spray or foam may be administered either by a hand pump or by an aerosolizing propellant. A second single phase formulation has also been developed. The formulation comprises a first drug which is water soluble or hydrophilic and a second drug which is lipid soluble or hydrophobic, wherein at least one of the drugs is bound to an ion-exchange resin. The use of binding resins, such as ion-exchange resins, allows drugs with incompatible solvent requirements to be prepared in a single-phase formulation.

摘要翻译： 已经开发了局部喷雾或泡沫，制备方法及其使用方法。 在一个优选的实施方案中，组合物包含一种或多种活性剂并且表现出抗菌活性和抗真菌活性。 可以加入赋形剂如化学消毒剂，抗瘙痒剂以最小化瘙痒和皮肤保护性化合物。 组合物可以配制成以喷雾或泡沫的形式分配，并且喷雾或泡沫可以通过手泵或雾化推进剂施用。 还开发了第二个单相制剂。 该制剂包含水溶性或亲水性的第一药物和脂溶性或疏水性的第二药物，其中至少一种药物与离子交换树脂结合。 使用结合树脂，例如离子交换树脂，可以在单相制剂中制备具有不相容溶剂要求的药物。

公开(公告)号：US07585520B2

公开(公告)日：2009-09-08

申请号：US10943311

申请日：2004-09-17

申请人： Mark Hirsh ,  Jane Hirsh ,  Whe-Yong Lo

发明人： Mark Hirsh ,  Jane Hirsh ,  Whe-Yong Lo

IPC分类号： A61K9/24 ,  A61K9/20 ,  A61K9/22 ,  A61K9/28 ,  A61K9/14

CPC分类号： A61K45/06 ,  A61K9/209 ,  A61K9/5084 ,  A61K31/00 ,  A61K2300/00

摘要： Compositions containing both a sedative compound and a non-sedative antihistamine are provided. More particularly, compositions for administration at bedtime containing a sedating antihistamine or other sedating compound in immediate release form and a non-sedating antihistamine in delayed-release form are described. Alternatively, a composition, for administrating upon awakening, containing a non-sedating antihistamine in immediate release form, and a sedating antihistamine or other sedative in delayed-release form is described. Methods of inhibiting the release of histamines by administration of the compositions to a mammalian subject are also provided. The dosage forms may comprise other medications, such as leukotriene receptor antagonists, to enhance the suppression of histamine symptoms.

摘要翻译： 提供了含有镇静化合物和非镇静抗组胺剂的组合物。 更具体地，描述了在睡前给药的组合物，其含有立即释放形式的镇静抗组胺药或其他镇静化合物和延迟释放形式的非镇静抗组胺药。 或者，描述了用于在觉醒时施用含有立即释放形式的非镇静抗组胺剂的组合物，以及缓释形式的镇静抗组胺药或其他镇静剂。 还提供了通过将哺乳动物受试者施用组合物来抑制组胺释放的方法。 剂型可以包含其他药物，例如白三烯受体拮抗剂，以增强组胺症状的抑制。

公开(公告)号：US20070232695A1

公开(公告)日：2007-10-04

申请号：US11534552

申请日：2006-09-22

申请人： Mark Hirsh ,  Jane Hirsh ,  Mark Trumbore

发明人： Mark Hirsh ,  Jane Hirsh ,  Mark Trumbore

IPC分类号： A61K31/325

CPC分类号： A61K31/325 ,  A61K9/006 ,  A61K9/0063 ,  A61K31/245 ,  A61K45/06 ,  A61K2300/00

摘要： A composition for anesthetizing oral or buccal tissues, especially periodontal pockets, is provided. The composition has a high concentration of topical anesthetic carried in a non-aqueous liquid vehicle containing a gelling agent. The anesthetics are optionally stabilized in the solution by ion-exchange complexation. The composition can anesthetize the gingivae for an extended period, such as 30 minutes or longer. Preferred anesthetics include tetracaine, benzocaine, butamben, and mixtures of these.

摘要翻译： 提供了用于麻醉口腔或颊组织，特别是牙周袋的组合物。 该组合物在含有胶凝剂的非水液体载体中携带高浓度的局部麻醉剂。 麻醉剂任选地通过离子交换络合稳定在溶液中。 组合物可以长时间麻醉牙龈，例如30分钟或更长时间。 优选的麻醉剂包括丁卡因，苯佐卡因，丁苯丁酸及其混合物。

公开(公告)号：US20090010869A9

公开(公告)日：2009-01-08

申请号：US11843158

申请日：2007-08-22

申请人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

发明人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

IPC分类号： A61K31/74 ,  A61K33/38 ,  A61K35/00 ,  A61K38/43 ,  A61P17/00

CPC分类号： A61K9/0014 ,  A61K9/12 ,  A61K33/18 ,  A61K33/38 ,  A61K36/48 ,  A61K38/482 ,  A61K38/4826 ,  A61K38/4873 ,  A61K38/4886 ,  A61K47/44 ,  A61L15/34 ,  A61L15/38 ,  A61L15/48 ,  A61K2300/00

摘要： Formulations are described for the treatment by enzymatic debridement of wounds and ulcers. The formulations have a clear, transparent composition that allows for easy visualization of the wound, and are non-staining for easy clean up. These formulations can also exhibit increased enzymatic debridement activity, improved post-treatment lubricity and coating occlusivity, and stability. The formulations, optionally containing non-animal source biologics, may be in the form of lotions, aerosols to provide a spray, or a foam. A non-reactive substrate may be used as a composition carrier. A non-aqueous lotion formulation having improved enzymatic activity is provided. The non-aqueous lotion viscosity is adjusted to achieve high enzymatic activity while maintaining the application benefits of high viscosity non-aqueous lotions. The lotion formulation may be delivered in a patch.

摘要翻译： 描述了用于通过创伤和溃疡的酶清除治疗的制剂。 制剂具有清晰，透明的组合物，其允许容易地观察伤口，并且是无污染的以便于清洁。 这些制剂还可以表现出增加的酶清除活性，改善的后处理润滑性和涂层封闭性以及稳定性。 任选地含有非动物源生物制剂的制剂可以是洗剂，提供喷雾剂或泡沫剂的气溶胶的形式。 非反应性底物可以用作组合物载体。 提供了具有改善的酶活性的非水性乳液制剂。 调节非水性乳液粘度以达到高酶活性，同时保持高粘度非水性乳液的应用益处。 洗剂制剂可以在贴剂中递送。

公开(公告)号：US20060188449A1

公开(公告)日：2006-08-24

申请号：US10565346

申请日：2004-10-04

申请人： Jane Hirsh ,  John Willis ,  Mark Hirsh

发明人： Jane Hirsh ,  John Willis ,  Mark Hirsh

IPC分类号： A61K31/573 ,  A61L9/04 ,  A61K31/56 ,  A61K31/24

CPC分类号： A61K31/24 ,  A61K9/0014 ,  A61K9/122 ,  A61K9/124 ,  A61K31/56 ,  A61K31/573

摘要： A stable topical aerosol foam is provided. The foam-forming formulation includes a HFA propellant and an active agent in an emulsion. The emulsion has an oil phase and an aqueous, i.e. water-containing, phase. The active agent may be present in either phase or dispersed in the emulsion. The oil phase may consist at least in part of the HFA propellant. Either or both of the oil phase and the aqueous phase may contain one or more surfactants, emulsifiers, emulsion stabilizers, buffers, and other excipients. In an alternative embodiment, the aqueous phase contains a water-soluble active agent, for example, a local anesthetic, and the oil phase contains a water-insoluble second active agent. The foam is stable on the skin, for example for at least 10 minutes at body temperature, and will disappear into the skin upon rubbing or after prolonged standing. The formulation has the advantage of an inert non-flammable hydrofluorocarbon propellant without requiring the use of additional co-solvents or co-propellants. The composition is administered to the skin or mucous membranes.

摘要翻译： 提供稳定的局部气溶胶泡沫。 泡沫形成制剂包括HFA推进剂和乳液中的活性剂。 乳液具有油相和含水相，即含水相。 活性剂可以以任一相存在或分散在乳液中。 油相可以至少部分地由HFA推进剂组成。 油相和水相中的任一种或两者可以含有一种或多种表面活性剂，乳化剂，乳液稳定剂，缓冲剂和其它赋形剂。 在另一个实施方案中，水相含有水溶性活性剂，例如局部麻醉剂，油相含有水不溶性第二活性剂。 泡沫在皮肤上是稳定的，例如在体温下至少10分钟，并且在摩擦或长时间放置后将消失在皮肤中。 该配方具有惰性不易燃氢氟烃推进剂的优点，而不需要使用额外的共溶剂或共推进剂。 将组合物施用于皮肤或粘膜。

公开(公告)号：US20050281806A1

公开(公告)日：2005-12-22

申请号：US11147567

申请日：2005-06-08

申请人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

发明人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

IPC分类号： A61K9/00 ,  A61K9/12 ,  A61K33/18 ,  A61K33/36 ,  A61K33/38 ,  A61K36/48 ,  A61K38/46 ,  A61K38/48 ,  A61K47/44 ,  A61K35/78

CPC分类号： A61K9/0014 ,  A61K9/12 ,  A61K33/18 ,  A61K33/38 ,  A61K36/48 ,  A61K38/482 ,  A61K38/4826 ,  A61K38/4873 ,  A61K38/4886 ,  A61K47/44 ,  A61L15/34 ,  A61L15/38 ,  A61L15/48 ,  A61K2300/00

摘要： Formulations are described for the treatment by enzymatic debridement of wounds and ulcers. The formulations have a clear, transparent composition that allows for easy visualization of the wound, and are non-staining for easy clean up. These formulations can also exhibit increased enzymatic debridement activity, improved post-treatment lubricity and coating occlusivity, and stability. The formulations, optionally containing non-animal source biologics, may be in the form of lotions, aerosols to provide a spray, or a foam. A non-reactive substrate may be used as a composition carrier. A non-aqueous lotion formulation having improved enzymatic activity is provided. The non-aqueous lotion viscosity is adjusted to achieve high enzymatic activity while maintaining the application benefits of high viscosity non-aqueous lotions. The lotion formulation may be delivered in a patch.

摘要翻译： 描述了用于通过创伤和溃疡的酶清除治疗的制剂。 制剂具有清晰，透明的组合物，其允许容易地观察伤口，并且是无污染的以便于清洁。 这些制剂还可以表现出增加的酶清除活性，改善的后处理润滑性和涂层封闭性以及稳定性。 任选地含有非动物源生物制剂的制剂可以是洗剂，提供喷雾剂或泡沫剂的气溶胶的形式。 非反应性底物可以用作组合物载体。 提供了具有改善的酶活性的非水性乳液制剂。 调节非水性乳液粘度以达到高酶活性，同时保持高粘度非水性乳液的应用益处。 洗剂制剂可以在贴剂中递送。

公开(公告)号：US06863901B2

公开(公告)日：2005-03-08

申请号：US10015930

申请日：2001-11-30

申请人： Jane Hirsh ,  Kamal Midha ,  Mark Hirsh ,  Whe-Yong Lo

发明人： Jane Hirsh ,  Kamal Midha ,  Mark Hirsh ,  Whe-Yong Lo

IPC分类号： A61J3/10 ,  A61K9/00 ,  A61K9/22 ,  A61K9/24 ,  A61K9/26 ,  A61K9/30 ,  A61K9/36 ,  A61K9/42 ,  A61K45/00 ,  A61K47/12 ,  A61K47/14 ,  A61K47/16 ,  A61K47/32 ,  A61K47/36 ,  A61K47/38 ,  A61K47/44 ,  A61P9/00 ,  A61P19/00 ,  A61P25/00 ,  A61P37/00 ,  A61K9/20 ,  A61K9/46

CPC分类号： A61K9/209 ,  A61K9/0056

摘要： New pharmaceutical compositions in unit dosage form are disclosed for both intraoral and oral administration to a patient, said unit dosage form configured to be placed intraorally of said patient, which comprises: (a) as a first portion, at least one discrete molded triturate tablet comprising a therapeutically effective amount of at least one pharmaceutically active ingredient capable of intraoral administration; and (b) as a second portion located around the said first portion, a therapeutically effective amount of at least one pharmaceutically active ingredient capable of oral administration and which is releasable and orally ingestible by the patient after the molded triturate tablet has disintegrated or has dissolved intraorally.

摘要翻译： 公开了单位剂量形式的新的药物组合物，用于向患者进行口内和口服给药，所述单位剂型被配置为置于所述患者的口内，其包括：（a）作为第一部分，至少一个离散的模制成型的片剂 包括治疗有效量的至少一种能口内给药的药物活性成分; 和（b）作为位于所述第一部分周围的第二部分，治疗有效量的至少一种能够口服给药的药学活性成分，并且其在模制的特定片剂崩解或溶解之后由患者可释放和口服摄入 口语

公开(公告)号：US20080014169A1

公开(公告)日：2008-01-17

申请号：US11843158

申请日：2007-08-22

申请人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

发明人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

IPC分类号： A61K31/74 ,  A61K33/38 ,  A61K35/00 ,  A61K38/43 ,  A61P17/00

CPC分类号： A61K9/0014 ,  A61K9/12 ,  A61K33/18 ,  A61K33/38 ,  A61K36/48 ,  A61K38/482 ,  A61K38/4826 ,  A61K38/4873 ,  A61K38/4886 ,  A61K47/44 ,  A61L15/34 ,  A61L15/38 ,  A61L15/48 ,  A61K2300/00

摘要： Formulations are described for the treatment by enzymatic debridement of wounds and ulcers. The formulations have a clear, transparent composition that allows for easy visualization of the wound, and are non-staining for easy clean up. These formulations can also exhibit increased enzymatic debridement activity, improved post-treatment lubricity and coating occlusivity, and stability. The formulations, optionally containing non-animal source biologics, may be in the form of lotions, aerosols to provide a spray, or a foam. A non-reactive substrate may be used as a composition carrier. A non-aqueous lotion formulation having improved enzymatic activity is provided. The non-aqueous lotion viscosity is adjusted to achieve high enzymatic activity while maintaining the application benefits of high viscosity non-aqueous lotions. The lotion formulation may be delivered in a patch.

摘要翻译： 描述了用于通过创伤和溃疡的酶清除治疗的制剂。 制剂具有清晰，透明的组合物，其允许容易地观察伤口，并且是无污染的以便于清洁。 这些制剂还可以表现出增加的酶清除活性，改善的后处理润滑性和涂层封闭性以及稳定性。 任选地含有非动物源生物制剂的制剂可以是洗剂，提供喷雾剂或泡沫剂的气溶胶的形式。 非反应性底物可以用作组合物载体。 提供了具有改善的酶活性的非水性乳液制剂。 调节非水性乳液粘度以达到高酶活性，同时保持高粘度非水性乳液的应用益处。 洗剂制剂可以在贴剂中递送。

公开(公告)号：US20070036843A1

公开(公告)日：2007-02-15

申请号：US11341016

申请日：2006-01-27

申请人： Jane Hirsh ,  Roman Rariy ,  Mark Trumbore ,  Alison Fleming ,  Mark Hirsh

发明人： Jane Hirsh ,  Roman Rariy ,  Mark Trumbore ,  Alison Fleming ,  Mark Hirsh

IPC分类号： A61K9/70 ,  A61K9/22

CPC分类号： A61K31/4402 ,  A61K9/006 ,  A61K9/5026 ,  A61K31/137 ,  A61K47/585

摘要： An improved controlled release composition for non-parenteral administration of active agents and other therapeutics, particularly for oral or topical administration, has been developed. The composition is made by dispersing a complex formed of an active agent bound to an ion-exchange resin or to another form of resin or carrier, in a non-ionic non-aqueous (“NINA”) vehicle. The complexes are optionally coated with one or more layers of coating material to provide a controlled pattern of release of active agent from the carrier. Replacing the usual aqueous vehicle with a NINA vehicle, such as an oil or an ointment, allows the active agent-carrier complexes, with or without coatings, to be both orally and topically administered. The compositions can be formulated as powders, liquids, liquid suspensions, gels, capsules, soft gelatin capsules, tablets, chewable tablets, topical ointments, lotions, pourable or pumpable fluids, semisolid, crushable tablets, and unit-of-use sachets or capsules for reconstitution or direct application. The combination of multiple active agents is possible with this system, in which one or more active agents are bound to particles and one or more active agents are dissolved or dispersed in the NINA vehicle. This allows the combination of two or more active agents, which are otherwise incompatible, into a single dosage form.

摘要翻译： 已经开发了用于非肠胃外给药活性剂和其它治疗剂，特别是用于口服或局部给药的改进的控释组合物。 该组合物通过在非离子非水（“NINA”）载体中分散由与离子交换树脂结合的活性剂形成的络合物或另一种形式的树脂或载体。 复合物任选地涂覆有一层或多层涂层材料，以提供活性剂从载体中释放的受控模式。 用诸如油或软膏的NINA载体代替普通的水性载体，允许具有或不具有涂层的活性剂 - 载体复合物均经口和局部施用。 组合物可以配制成粉末，液体，液体悬浮液，凝胶，胶囊，软明胶胶囊，片剂，咀嚼片，局部软膏，洗剂，可倾倒或可泵送的液体，半固体，可压碎片剂和单位使用的小袋或胶囊 用于重组或直接应用。 该系统可以使用多种活性剂的组合，其中一种或多种活性剂与颗粒结合，一种或多种活性剂溶解或分散在NINA载体中。 这允许将两种或更多种否则不相容的活性剂组合成单一剂型。