CN1111509A - 含氯林可霉素棕榈酸酯的延迟释放剂型 - Google Patents
含氯林可霉素棕榈酸酯的延迟释放剂型 Download PDFInfo
- Publication number
- CN1111509A CN1111509A CN95101443A CN95101443A CN1111509A CN 1111509 A CN1111509 A CN 1111509A CN 95101443 A CN95101443 A CN 95101443A CN 95101443 A CN95101443 A CN 95101443A CN 1111509 A CN1111509 A CN 1111509A
- Authority
- CN
- China
- Prior art keywords
- clindamycin
- clindamycin palmitate
- palmitate
- implant
- tangible
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
本发明涉及用氯林可霉素棕榈酸酯制备延迟释
放抗菌活性化合物氯林可霉素的药物剂型,以及相应
的药物剂型,优选以有形植入物的剂型使用。
Description
本发明涉及用氯林可霉素棕榈酸酯制备延迟释放抗菌活性化合物氯林可霉素的药物剂型,以及相应的药物剂型,特别是有形植入物的剂型。
氯林可霉素是通常公认有价值的抗菌素。它对于革兰阳性生物体如葡萄球菌和链球菌以及革兰阴性厌氧菌特别有效。因此该抗菌素用于治疗广谱疾病,例如控制消化道、皮肤和软组织感染,还可用于治疗脊髓炎和妇科感染。此外氯林可霉素成功地用于预防和治疗细菌性心内膜炎。
在上述适应症中,该抗菌素以生理可接受的盐如氯林可霉素盐酸盐、氯林可霉素磷酸盐或游离氯林可霉素碱的形式使用。
棕榈酸酯形式的氯林可霉素也是已知的。氯林可霉素棕榈酸酯本身是微生物学惰性的。但是它容易被小肠的酶水解,并从该形式释放出活性氯林可霉素碱。该活性化合物的血浆半衰期是约2小时。由于这种性质,发现以盐酸盐形式使用氯林可霉素棕榈酸酯易溶于含水介质中,作为快速和短期作用的抗菌素治疗形式,该活性化合物口服给药。游离的氯林可霉素棕榈酸酯(即非盐酸盐形式)实际上不溶于含水介质中,因此直到现在仍然是药理学上不重要的。
现在出人意料地发现,氯林可霉素棕榈酸酯不仅可以在胃肠道水解成活性氯林可霉素,也可以在体液如血清和血液的影响下在身体的其他部位发生水解。通过体外实验发现在血清或全血中或在巨噬细胞影响下,活性氯林可霉素在几天至几周时间内,以大约恒定的速度缓慢地从氯林可霉素棕榈酸酯释放出来。由于这些发现,形成了氯林可霉素棕榈酸酯本身作为储存抗菌素局部使用(例如用于手术创伤部位)以用于预防和治疗感染的基本适应性,它可以延迟释放活性化合物氯林可霉素。
氯林可霉素棕榈酸酯尤其适用于制备可延迟释放抗菌活性化合物氯林可霉素的药物剂型。
因此本发明涉及用氯林可霉素棕榈酸酯制备延迟释放抗菌活性化合物氯林可霉素的药物剂型。
本发明还涉及延迟释放抗菌活性化合物氯林可霉素的药物剂型,这些剂型含有氯林可霉素棕榈酸酯。
本发明尤其涉及有形植入物形式的药物剂型。
本发明氯林可霉素棕榈酸酯作为储存抗菌素用于制备延迟释放活性化合物的剂型的适用性,一方面是由于其在含水介质和生理介质中的低溶解性,另一方面是由于迄今尚未发现的其通过体液代谢过程释放出活性氯林可霉素碱以及可以显示其抗菌素活性。在体外研究中,例如于大鼠血液中培养4小时后氯林可霉素棕榈酸酯水解达70%,24小时后水解达100%。在人血清和马血清中,在此阶段后35%该酯裂解为活性氯林可霉素碱。给大鼠的股肌植入数片氯林可霉素棕榈酸酯浸透的PTFE无纺布进行体内实验,实验表明在14天内动物尿中的氯林可霉素碱的分泌是恒定至少量增加的,同时未检出氯林可霉素棕榈酸酯。此外在植入物周围的肌肉组织中可以检测到氯林可霉素碱。
根据本发明,氯林可霉素棕榈酸酯可以有利的用于延迟释放活性化合物氯林可霉素的药物剂型中。此类药物剂型优选制成有形植入物形式。这些有形植入物主要用于骨替代治疗或恢复由意外伤害或疾病引起的骨损伤。此外相应的有形植入物还可以用于替代其他器官部分,例如人工心脏瓣膜、人工瓣膜缝合环、人造血管或其他外科缝合材料。有形植入物还可以仅仅用作局部释放活性化合物以控制或预防感染的储存植入物。
有利的是,此类有形植入物含有5-250mg/cm3氯林可霉素棕榈酸酯。在此浓度范围内,对于常规的适应症可保证释放活性量的氯林可霉素持续足够长的时间。
氯林可霉素棕榈酸酯与一种或多种其他药物活性成分结合是有利的,尤其是那些也具有抗菌作用的。在这种情况下,抗菌作用谱可以被加宽和/或暂时和定量所合并的不同抗菌素的不同释放速度。
可以与氯林可霉素棕榈酸酯结合的此类抗菌素的其他实例是硫酸庆大霉素,以及特别是庆大霉素与3-对甲氧基亚苄基-6-羟基-4′-甲氧基-黄烷酮-6-磷酸的盐。后一庆大霉素盐是难溶的,因此提供了延迟释放的庆大霉素储存剂型。
本发明氯林可酶素棕榈酸酯用于制备延迟释放药物剂型的用途可以方便地通过用氯林可霉素棕榈酸酯浸透合适的载体材料进行,该载体材料以有形植入物的形式出现或者可以进一步加工成有形植入物,这样其游离的外表面,以及如果需要,其内表面和/或基质材料尽可能均匀地载负活性化合物。该渗透可以方便地用氯林可霉素棕榈酸酯液体制剂进行,该液体制剂容易湿润或渗入有形植入物。所述液体制剂可以是活性化合物的悬浮液或优选溶液。
研究发现,7-9份体积四氢呋喃和3-1份体积水的混合物是氯林可霉素棕榈酸酯的特别好的溶剂。在此类四氢呋喃/水的混合物中,氯林可霉素可被溶解至约33%重量。如果氯林可霉素棕榈酸酯与上述储存形式的庆大霉素结合使用,这类溶剂混合物也是特别有益的。根据德国专利申请P4314871,该类型的混合物对于庆大霉素盐是极好的溶剂,否则庆大霉素盐将仅仅是难溶的。
适用于氯林可霉素棕榈酸酯和可能的其他药物活性化合物的载体材料主要是多孔材料,该材料容易吸收活性化合物溶液。生物活性以及特别是生物可吸收的材料是优选的,它们优选为有形植入的形式或者可以被进一步加工成有形植入物。有形植入物的典型多孔生物材料是磷酸钙,特别是例如磷酸钙陶瓷。通常这些材料由合成的或天然的羟基磷灰石组成。骨灰磁是优选的,它可以这样获得,即从天然骨中除去有机部分并烧结矿物相得到该陶瓷。由于泡沫陶瓷的天然高孔隙度,它特别适合于用活性化合物浸润。其他磷酸钙材料是磷酸三钙和磷酸四钙,它们也可以被相似地利用。
生物惰性聚合材料例如聚四氟乙烯(“Teflon”)或生物聚合物例如胶原、明胶、几丁质、脱乙酰几丁质、聚交酯、聚乙交酯的多孔模制植入物也可以按照本发明的方法用氯林可霉素棕榈酸酯浸润。优选地,这些材料为具有多孔非纺织或纺织纤维结构的吸收性结构形式,或者是凝胶或蜡质材料。由生物陶瓷和生物聚合物制备的多孔复合材料也适于用作活性化合物的载体。
使多孔活性化合物载体载负氯林可霉素棕榈酸酯可以方便地如下进行,即通过用活性化合物溶液浸润或滴加至有吸收力的体积完全被溶液充满,对该载体进行处理。然后将载体干燥,优选用热空气流干燥。对于四氢呋喃,干燥较快速地发生,这样可以使大部分溶剂混合物快速蒸发。通过这种方法,有形植入物的内、外表面涂上一层活性化合物,该涂层是均匀的,从而达到最大可能的容量。在某些情况下如何需要进行灭菌,之后无菌包装,则载负有活性化合物的有形植入物已预制备用。
按照用氯林可霉素棕榈酸酯处理的类似方法,非多孔或仅仅粗表面的植入物也可以用活性化合物层涂覆。此类延迟释放活性化合物的抗菌素涂层对于由金属、陶瓷或塑料制备的许多种内假体(en-doprostheses)是有利的。除了该溶液的高活性化合物浓度外,在此情况下该涂层的附加优点是:它能够快速润湿并均匀地涂覆这些材料。例如,髋假体的股骨体抗菌素涂层以及心脏瓣膜缝合环的抗菌素浸润是有益的。
用含有氯林可霉素棕榈酸酯的有形植入物进行的体外和体内实验表明:延迟、均匀地释放抗菌活性氯林可霉素碱,同时未表明释放出非活性的氯林可霉素棕榈酸酯,或仅仅表明释放出极少量的氯林可霉素棕榈酸酯。
实施例1
从在25ml水中的1g氯林可霉素棕榈酸酯盐酸盐溶液开始,通过加入10ml 0.1%当量NaOH溶液使氯林可霉素棕榈酸酯沉淀,滤出,用水洗涤并干燥。
实施例2
将0.1g实施例1的氯林可霉素棕榈酸酯悬浮于100ml 1.5%液体琼脂溶液中。固化后,将该材料切成约0.725cm3的有形制品。
用新鲜的活性人血清洗脱这些有形制品。对洗脱液中氯林可霉素的活性进行生物学测定。结果表明在多于20天的时间内以大约10μg/ml的浓度零级释放。
实施例3
在25℃和搅拌条件下,将实施例1的氯林可霉素棕榈酸酯溶于9份体积THF和1份体积水的混合物中,得到含0.33g/ml氯林可霉素棕榈酸酯的溶液。
实施例4
从天然海绵矿物制备12.5×12.5×10mm尺寸的多孔羟基磷灰石陶瓷块,用实施例3的溶液将其浸透。取出用该溶液饱和的陶瓷块,在热空气流中干燥2小时。该预制备用的陶瓷块含有约120mg氯林可霉素棕榈酸酯。
实施例5
将直径0.5cm和厚0.2cm的圆形Teflon无纺布浸入实施例3的溶液中,直到其完全饱和。然后将其取出,并在热空气流中干燥约30分钟。该预制备用的无防布含有25mg氯林可霉素棕榈酸酯。
实施例6
在6只大鼠的股肌中植入实施例5的Teflon无防布。将动物放入代谢笼内。在2周期间内每天对所收集的尿进行抗菌素释放测定。
图1表明了该结果。
在试验期间,在尿中未检测到氯林可霉素棕榈酸酯,但是测得抗菌活性的氯林可霉素略微增加,从16至32μg/ml。
实施例7
首先用含有0.33g/ml氯林可霉素棕榈酸酯和0.1g/ml庆大霉素与3-对甲氧基亚苄基-6-羟基-4′-甲氧基-黄烷酮-6-磷酸的盐的9份体积THF和1份体积水的溶液浸润心脏瓣膜缝合环片段(Sorin,Italy),并干燥。然后将此片段浸入含0.03g/ml硫酸庆大霉素的水溶液中,并再次干燥。以此方式得到缝合环片段,它含有20mg氯林可霉素棕榈酸酯、14mg难溶的庆大霉素盐和4mg硫酸庆大霉素。
将这些片段植入5只大鼠的股肌中。将动物放入代谢笼内。在2周期间内每天对所收集的尿进行抗菌素释放测定。
图2表明了该结果。
在试验期间,在尿中未检测到氯林可霉素棕榈酸酯,但是测得约14μg/ml恒定含量的氯林可霉素。庆大霉素的释放曲线表明:在最初24小时内初始峰值为290μg/ml,随后延迟释放,从38μg/ml降至3.5μg/ml。
Claims (10)
1、用氯林可霉素棕榈酸酯制备延迟释放抗菌活性化合物氯林可霉素的药物剂型的用途。
2、延迟释放抗菌活性化合物氯林可霉素的药物剂型,其特征在于它含有氯林可霉素棕榈酸酯。
3、根据权利要求2的药物剂型,其特征在于它是有形植入物。
4、根据权利要求3的有形植入物,其特征在于它含有5-250mg/cm3氯林可霉素棕榈酸酯。
5、根据权利要求3或4的有形植入物,其特征在于它含有与一种或多种其他药物活性化合物、特别是具有抗菌作用的化合物结合的氯林可霉素棕榈酸酯。
6、根据权利要求5的有形植入物,其特征在于它含有与硫酸庆大霉素和/或庆大霉素与3-对甲氧基亚苄基-6-羟基-4′-甲氧基-黄烷酮-6-磷酸的盐结合的氯林可霉素棕榈酸酯。
7、根据权利要求3-6的有形植入物,其特征在于它由用氯林可霉素棕榈酸酯浸透的活性化合物载体组成。
8、根据权利要求7的有形植入物,其特征在于该活性化合物载体由生物惰性或生物可吸收的聚合材料组成,该材料是多孔的非纺织或纺织纤维结构。
9、根据权利要求7的有形植入物,其特征在于该活性化合物载体由多孔陶瓷材料、特别是磷酸钙基的材料组成。
10、制备可植入的延迟释放抗菌活性化合物氯林可霉素的药物剂型的方法,其特征在于将氯林可霉素棕榈酸酯,以及如果需要,将其他药物活性化合物溶于7-9份体积四氢呋喃和3-1份体积水的混合物中,用该溶液处理活性化合物载体,然后干燥除去溶剂。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEP4404018.0 | 1994-02-09 | ||
DE4404018A DE4404018A1 (de) | 1994-02-09 | 1994-02-09 | Protrahiert freisetzende Darreichungsformen enthaltend Clindamycin-Palmitat |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1111509A true CN1111509A (zh) | 1995-11-15 |
Family
ID=6509827
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN95101443A Pending CN1111509A (zh) | 1994-02-09 | 1995-01-31 | 含氯林可霉素棕榈酸酯的延迟释放剂型 |
Country Status (11)
Country | Link |
---|---|
US (1) | US5607685A (zh) |
EP (1) | EP0667161B1 (zh) |
JP (1) | JPH07277992A (zh) |
KR (1) | KR950031055A (zh) |
CN (1) | CN1111509A (zh) |
AT (1) | ATE177639T1 (zh) |
CZ (1) | CZ32695A3 (zh) |
DE (2) | DE4404018A1 (zh) |
ES (1) | ES2130455T3 (zh) |
PL (1) | PL179298B1 (zh) |
TW (1) | TW282405B (zh) |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006111636A (ja) * | 1997-12-26 | 2006-04-27 | Astellas Pharma Inc | 徐放性医薬組成物 |
DE19856668A1 (de) * | 1998-12-09 | 2000-06-15 | Aesculap Ag & Co Kg | Wirkstoffmatrix in Form eines biologisch resorbierbaren porösen Vlieses, Verfahren zu ihrer Herstellung und Verwendung |
US7169373B2 (en) * | 1999-07-14 | 2007-01-30 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) having calcium phosphate whisker on surface and process for preparing the same |
US7270705B2 (en) * | 1999-07-14 | 2007-09-18 | Jiin-Huey Chern Lin | Method of increasing working time of tetracalcium phosphate cement paste |
US7094282B2 (en) * | 2000-07-13 | 2006-08-22 | Calcitec, Inc. | Calcium phosphate cement, use and preparation thereof |
US6840995B2 (en) * | 1999-07-14 | 2005-01-11 | Calcitec, Inc. | Process for producing fast-setting, bioresorbable calcium phosphate cements |
US6960249B2 (en) * | 1999-07-14 | 2005-11-01 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) having calcium phosphate whisker on surface |
US6544555B2 (en) * | 2000-02-24 | 2003-04-08 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
US6565882B2 (en) * | 2000-02-24 | 2003-05-20 | Advancis Pharmaceutical Corp | Antibiotic composition with inhibitor |
US7204876B2 (en) * | 2000-07-13 | 2007-04-17 | Calcitec, Inc. | Calcium phosphate cements made from (TTCP) with surface whiskers and process for preparing same |
US7156915B2 (en) * | 2000-07-13 | 2007-01-02 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) with surface whiskers and method of making same |
US6541014B2 (en) * | 2000-10-13 | 2003-04-01 | Advancis Pharmaceutical Corp. | Antiviral product, use and formulation thereof |
US20020068078A1 (en) * | 2000-10-13 | 2002-06-06 | Rudnic Edward M. | Antifungal product, use and formulation thereof |
US20020197314A1 (en) * | 2001-02-23 | 2002-12-26 | Rudnic Edward M. | Anti-fungal composition |
DE10114364A1 (de) * | 2001-03-22 | 2002-10-02 | Heraeus Kulzer Gmbh & Co Kg | Verfahren zur Herstellung von antibiotischen Kompositen |
DE10114244A1 (de) * | 2001-03-22 | 2002-10-02 | Heraeus Kulzer Gmbh & Co Kg | Antibiotikum-/Antibiotika-Zubereitung mit retardierender Wirkstofffreisetzung |
DE10114245A1 (de) * | 2001-03-22 | 2002-10-02 | Heraeus Kulzer Gmbh & Co Kg | Herstellung und Verwendung einer Antibiotikum-/Antibiotika-Zubereitung |
IS6390A (is) | 2001-08-31 | 2003-03-03 | Heraeus Kulzer Gmbh & Co. Kg | Reynsla af sýklalyfjahúðun skrokka sem í eru örholrými, þannig húðuðum skrokkum og einnig af notkunþeirra |
US20040131754A1 (en) * | 2001-10-24 | 2004-07-08 | Howmedica Osteonics Corp. | Antibiotic calcium phosphate coating |
US6596338B2 (en) * | 2001-10-24 | 2003-07-22 | Howmedica Osteonics Corp. | Antibiotic calcium phosphate coating |
WO2003053402A1 (en) * | 2001-12-20 | 2003-07-03 | Pharmacia Corporation | Zero-order sustained released dosage forms and method of making the same |
US20030216777A1 (en) * | 2002-05-16 | 2003-11-20 | Yin-Chun Tien | Method of enhancing healing of interfacial gap between bone and tendon or ligament |
DE10262176B4 (de) * | 2002-06-21 | 2007-10-04 | Heraeus Kulzer Gmbh | Verfahren zur Herstellung von antibiotisch beschichteten porösen Körpern sowie Verwendung |
CA2501324A1 (en) * | 2002-10-30 | 2004-05-21 | Pharmacia Corporation | Oral extended release tablets and methods of making and using the same |
US8313776B2 (en) * | 2003-07-21 | 2012-11-20 | Shionogi Inc. | Antibiotic product, use and formulation thereof |
EP1648418A4 (en) * | 2003-07-21 | 2011-11-16 | Middlebrook Pharmaceuticals Inc | ANTIBIOTIC PRODUCT, ITS USE AND FORMULATION |
AU2004258953B2 (en) * | 2003-07-21 | 2011-02-10 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
US7163651B2 (en) * | 2004-02-19 | 2007-01-16 | Calcitec, Inc. | Method for making a porous calcium phosphate article |
US7118705B2 (en) * | 2003-08-05 | 2006-10-10 | Calcitec, Inc. | Method for making a molded calcium phosphate article |
US6994726B2 (en) * | 2004-05-25 | 2006-02-07 | Calcitec, Inc. | Dual function prosthetic bone implant and method for preparing the same |
EP1653925A1 (en) * | 2003-08-11 | 2006-05-10 | Advancis Pharmaceutical Corporation | Robust pellet |
AU2004264356B2 (en) | 2003-08-12 | 2011-01-27 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
JP5686494B2 (ja) * | 2003-08-29 | 2015-03-18 | シオノギ インコーポレイテッド | 抗生物質製剤、その使用法及び作成方法 |
WO2005027877A1 (en) * | 2003-09-15 | 2005-03-31 | Advancis Pharmaceutical Corporation | Antibiotic product, use and formulation thereof |
US20050101964A1 (en) * | 2003-11-07 | 2005-05-12 | Calcitec, Inc. | Spinal fusion procedure using an injectable bone substitute |
EP1701705A4 (en) * | 2003-12-24 | 2007-08-08 | Advancis Pharmaceutical Corp | IMPROVED ABSORPTION OF MODIFIED RELEASE DOSAGE FORMS |
JP2008505124A (ja) * | 2004-07-02 | 2008-02-21 | アドバンシス ファーマスーティカル コーポレイション | パルス送達用錠剤 |
DE102005002703C5 (de) | 2005-01-19 | 2013-07-04 | Heraeus Kulzer Gmbh | Antibiotische Beschichtung von Implantaten sowie Verfahren zur antibiotischen Beschichtung |
US20070213835A1 (en) * | 2005-11-04 | 2007-09-13 | Markus Wimmer | Plastic implant impregnated with an antibiotic |
US8778924B2 (en) * | 2006-12-04 | 2014-07-15 | Shionogi Inc. | Modified release amoxicillin products |
US8357394B2 (en) | 2005-12-08 | 2013-01-22 | Shionogi Inc. | Compositions and methods for improved efficacy of penicillin-type antibiotics |
DE102006007245A1 (de) * | 2006-02-15 | 2007-08-23 | Heraeus Kulzer Gmbh | Implantatmaterial |
DE102006016598A1 (de) * | 2006-04-06 | 2007-11-15 | Heraeus Kulzer Gmbh | Beschichtete Vaskulärimplantate |
US8299052B2 (en) | 2006-05-05 | 2012-10-30 | Shionogi Inc. | Pharmaceutical compositions and methods for improved bacterial eradication |
DE102007063395A1 (de) * | 2007-12-31 | 2009-07-02 | Ossacur Ag | Transport-, Weitergabe- und/oder Wirksystem in aseptischer Darreichung |
DE102010020940B4 (de) | 2010-05-19 | 2014-09-25 | Heraeus Medical Gmbh | Antibiotische Beschichtung |
DE102010055559B4 (de) | 2010-12-23 | 2015-10-29 | Heraeus Medical Gmbh | Beschichtungsverfahren und Beschichtungsvorrichtung |
DE102010055562B4 (de) | 2010-12-23 | 2015-07-09 | Heraeus Medical Gmbh | Beschichtungsvorrichtung und Beschichtungsverfahren |
DE102010055561B4 (de) | 2010-12-23 | 2015-12-31 | Heraeus Medical Gmbh | Beschichtungsverfahren und Beschichtungsvorrichtung |
DE102010055560B4 (de) | 2010-12-23 | 2017-02-23 | Heraeus Medical Gmbh | Beschichtungsvorrichtung |
WO2012177986A2 (en) | 2011-06-22 | 2012-12-27 | Vyome Biosciences | Conjugate-based antifungal and antibacterial prodrugs |
DE102011117526B4 (de) | 2011-11-03 | 2015-07-30 | Heraeus Medical Gmbh | Beschichtungsverfahren und Beschichtungsvorrichtung für medizinische Implantate |
CN114230619A (zh) * | 2022-01-05 | 2022-03-25 | 浙江天台药业股份有限公司 | 一种盐酸克林霉素棕榈酸酯杂质的分离纯化方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4539234A (en) * | 1981-05-27 | 1985-09-03 | Unitika Ltd. | Urethral catheter capable of preventing urinary tract infection and process for producing the same |
US5202128A (en) * | 1989-01-06 | 1993-04-13 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
AU1579092A (en) * | 1991-02-27 | 1992-10-06 | Nova Pharmaceutical Corporation | Anti-infective and anti-inflammatory releasing systems for medical devices |
AU1797592A (en) * | 1991-04-12 | 1992-11-17 | Upjohn Company, The | Vaginal drug delivery device |
-
1994
- 1994-02-09 DE DE4404018A patent/DE4404018A1/de not_active Withdrawn
-
1995
- 1995-01-26 DE DE59505344T patent/DE59505344D1/de not_active Expired - Lifetime
- 1995-01-26 TW TW084100701A patent/TW282405B/zh active
- 1995-01-26 AT AT95101011T patent/ATE177639T1/de active
- 1995-01-26 EP EP95101011A patent/EP0667161B1/de not_active Expired - Lifetime
- 1995-01-26 ES ES95101011T patent/ES2130455T3/es not_active Expired - Lifetime
- 1995-01-31 CN CN95101443A patent/CN1111509A/zh active Pending
- 1995-02-06 KR KR1019950002043A patent/KR950031055A/ko not_active Application Discontinuation
- 1995-02-07 JP JP7019396A patent/JPH07277992A/ja not_active Withdrawn
- 1995-02-08 US US08/385,428 patent/US5607685A/en not_active Expired - Lifetime
- 1995-02-08 PL PL95307159A patent/PL179298B1/pl unknown
- 1995-02-08 CZ CZ95326A patent/CZ32695A3/cs unknown
Also Published As
Publication number | Publication date |
---|---|
ES2130455T3 (es) | 1999-07-01 |
JPH07277992A (ja) | 1995-10-24 |
ATE177639T1 (de) | 1999-04-15 |
PL307159A1 (en) | 1995-08-21 |
DE59505344D1 (de) | 1999-04-22 |
EP0667161A1 (de) | 1995-08-16 |
KR950031055A (ko) | 1995-12-18 |
CZ32695A3 (en) | 1995-10-18 |
EP0667161B1 (de) | 1999-03-17 |
PL179298B1 (pl) | 2000-08-31 |
US5607685A (en) | 1997-03-04 |
TW282405B (zh) | 1996-08-01 |
DE4404018A1 (de) | 1995-08-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1111509A (zh) | 含氯林可霉素棕榈酸酯的延迟释放剂型 | |
Lee et al. | Application of materials as medical devices with localized drug delivery capabilities for enhanced wound repair | |
US10500317B2 (en) | Antibacterial coatings that inhibit biofilm formation on implants | |
US8546529B2 (en) | Injectable bone regeneration gel containing bone formation enhancing peptide | |
Ruszczak et al. | Collagen as a carrier for on-site delivery of antibacterial drugs | |
US4975526A (en) | Bone collagen matrix for zenogenic implants | |
US6110205A (en) | Implant material having an excipient/active compound combination | |
CN103705294B (zh) | 多功能复合药物涂层缓释系统及其制备方法 | |
CA2200052A1 (en) | Bone-forming graft | |
WO1996003165A1 (en) | Prostheses for the abdominal wall | |
CN104105500A (zh) | 基于牛磺罗定和鱼精蛋白组合的广谱抗微生物组合物以及包含此类组合物的医疗装置 | |
CN110234365A (zh) | 医学植入物和涂覆医学植入物的方法 | |
US20200246511A1 (en) | Methods and devices to reduce the risk of infection | |
JPH05503286A (ja) | 骨における薬物送達のための生体侵食性ポリマー | |
KR20170056783A (ko) | 항생제 및 성장인자가 탑재된 bcp계 마이크로채널 주사형 뼈 이식재 | |
EP0652017A1 (de) | Beschichtung für Biomaterial | |
EP2953657B1 (en) | Tissue substitute material with biologically active coating | |
JPH04327525A (ja) | 徐放性薬剤含有セラミックス多孔体 | |
RU2260446C2 (ru) | Эндопротез с долговременной стабильностью | |
WO2020051646A1 (en) | Artificial periosteum | |
KR20150000670A (ko) | 표면에 생리활성 물질이 고정된 임플란트의 제조방법 및 이에 따라 제조된 임플란트 | |
TWI697335B (zh) | 藥物載體組合、藥物組合物、其用途、其製備方法及其使用方法 | |
KR102666722B1 (ko) | 약물 캐리어의 조성물, 그 의약적 조성물, 그 제조 방법 및 이용 방법 | |
KR101943432B1 (ko) | 서방성 주사용 골 이식재의 제조방법 | |
CN111228216B (zh) | 药物载体组合、药物组合物、其用途、其制备方法及其使用方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
AD01 | Patent right deemed abandoned | ||
C20 | Patent right or utility model deemed to be abandoned or is abandoned |