CN1345213A - 具有烟碱并添加单萜酮的经皮治疗系统 - Google Patents
具有烟碱并添加单萜酮的经皮治疗系统 Download PDFInfo
- Publication number
- CN1345213A CN1345213A CN00805525A CN00805525A CN1345213A CN 1345213 A CN1345213 A CN 1345213A CN 00805525 A CN00805525 A CN 00805525A CN 00805525 A CN00805525 A CN 00805525A CN 1345213 A CN1345213 A CN 1345213A
- Authority
- CN
- China
- Prior art keywords
- therapeutic system
- nicotine
- quintessence oil
- monoterpene ketone
- menthone
- 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.)
- Granted
Links
- 229930003658 monoterpene Natural products 0.000 title claims abstract description 44
- 235000002577 monoterpenes Nutrition 0.000 title claims abstract description 44
- -1 monoterpene ketones Chemical class 0.000 title claims abstract description 43
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 title claims abstract description 41
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 229960002715 nicotine Drugs 0.000 title claims abstract description 41
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 18
- 239000010410 layer Substances 0.000 claims abstract 4
- 230000001070 adhesive effect Effects 0.000 claims abstract 2
- 239000011241 protective layer Substances 0.000 claims abstract 2
- 230000002159 abnormal effect Effects 0.000 claims description 28
- 230000035943 smell Effects 0.000 claims description 28
- ULDHMXUKGWMISQ-UHFFFAOYSA-N carvone Chemical compound CC(=C)C1CC=C(C)C(=O)C1 ULDHMXUKGWMISQ-UHFFFAOYSA-N 0.000 claims description 26
- NFLGAXVYCFJBMK-UHFFFAOYSA-N Menthone Chemical compound CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 claims description 23
- NFLGAXVYCFJBMK-RKDXNWHRSA-N (+)-isomenthone Natural products CC(C)[C@H]1CC[C@@H](C)CC1=O NFLGAXVYCFJBMK-RKDXNWHRSA-N 0.000 claims description 13
- 239000005973 Carvone Substances 0.000 claims description 13
- 229930007503 menthone Natural products 0.000 claims description 13
- NFLGAXVYCFJBMK-IUCAKERBSA-N (-)-isomenthone Chemical compound CC(C)[C@@H]1CC[C@H](C)CC1=O NFLGAXVYCFJBMK-IUCAKERBSA-N 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- NZGWDASTMWDZIW-MRVPVSSYSA-N (+)-pulegone Chemical compound C[C@@H]1CCC(=C(C)C)C(=O)C1 NZGWDASTMWDZIW-MRVPVSSYSA-N 0.000 claims description 7
- NZGWDASTMWDZIW-UHFFFAOYSA-N Pulegone Natural products CC1CCC(=C(C)C)C(=O)C1 NZGWDASTMWDZIW-UHFFFAOYSA-N 0.000 claims description 7
- USMNOWBWPHYOEA-UHFFFAOYSA-N alpha-thujone Natural products CC1C(=O)CC2(C(C)C)C1C2 USMNOWBWPHYOEA-UHFFFAOYSA-N 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 229930007459 p-menth-8-en-3-one Natural products 0.000 claims description 7
- 239000000758 substrate Substances 0.000 claims description 7
- YSTPAHQEHQSRJD-UHFFFAOYSA-N 3-Carvomenthenone Chemical compound CC(C)C1CCC(C)=CC1=O YSTPAHQEHQSRJD-UHFFFAOYSA-N 0.000 claims description 6
- 229930006968 piperitone Natural products 0.000 claims description 6
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims 1
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 1
- 239000011707 mineral Substances 0.000 claims 1
- 235000006679 Mentha X verticillata Nutrition 0.000 abstract description 2
- 235000002899 Mentha suaveolens Nutrition 0.000 abstract description 2
- 235000001636 Mentha x rotundifolia Nutrition 0.000 abstract description 2
- 239000000341 volatile oil Substances 0.000 abstract 2
- 239000003921 oil Substances 0.000 description 32
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 14
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 11
- 229940041616 menthol Drugs 0.000 description 9
- 239000000654 additive Substances 0.000 description 8
- 241000894007 species Species 0.000 description 8
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 6
- NFLGAXVYCFJBMK-BDAKNGLRSA-N (-)-menthone Chemical compound CC(C)[C@@H]1CC[C@@H](C)CC1=O NFLGAXVYCFJBMK-BDAKNGLRSA-N 0.000 description 6
- 230000000996 additive effect Effects 0.000 description 5
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 3
- 244000246386 Mentha pulegium Species 0.000 description 3
- 235000016257 Mentha pulegium Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229960005233 cineole Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229960004873 levomenthol Drugs 0.000 description 3
- 150000002773 monoterpene derivatives Chemical class 0.000 description 3
- 235000007586 terpenes Nutrition 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- RFFOTVCVTJUTAD-UHFFFAOYSA-N cineole Natural products C1CC2(C)CCC1(C(C)C)O2 RFFOTVCVTJUTAD-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000003097 mucus Anatomy 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000012744 reinforcing agent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003505 terpenes Chemical class 0.000 description 2
- 150000003648 triterpenes Chemical class 0.000 description 2
- JGVWYJDASSSGEK-UHFFFAOYSA-N 5-methyl-2-propan-2-ylidenecyclohexan-1-ol Chemical compound CC1CCC(=C(C)C)C(O)C1 JGVWYJDASSSGEK-UHFFFAOYSA-N 0.000 description 1
- 101100232929 Caenorhabditis elegans pat-4 gene Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 235000008418 Hedeoma Nutrition 0.000 description 1
- NOOLISFMXDJSKH-OPRDCNLKSA-N Isomenthol Chemical compound CC(C)[C@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-OPRDCNLKSA-N 0.000 description 1
- NOOLISFMXDJSKH-LPEHRKFASA-N Isomenthol Natural products CC(C)[C@@H]1CC[C@H](C)C[C@H]1O NOOLISFMXDJSKH-LPEHRKFASA-N 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 235000005135 Micromeria juliana Nutrition 0.000 description 1
- 240000002114 Satureja hortensis Species 0.000 description 1
- 235000007315 Satureja hortensis Nutrition 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 125000002272 menthone group Chemical group 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930007461 neoisomenthol Natural products 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000010913 used oil Substances 0.000 description 1
Images
Classifications
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/465—Nicotine; Derivatives thereof
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Addiction (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
一种经皮治疗系统,它具有一个背层、至少一个含有尼古丁层或矿物区域,它也能呈现粘附性质,以及一个可重复移除和再施加的保护层,其特征在于含有至少一种得自薄荷的精油或在这种精油中找到的单萜酮。
Description
本发明是关于添加气味改进物质至含有烟碱的经皮治疗系统(TTSs)中。更具体地，它是关于包含此类添加物的含有烟碱的TTSs，以及用以掩盖这种TTSs的令人不愉快气味的方法，并且关于气味改进物质的用途，用以掩盖因烟碱含量所引起的这种TTSs的令人不愉快的气味。
在全世界，含有烟碱的TTSs是广泛地被用于戒烟的治疗上。然而，在市场上可获得的系统显示明显的烟碱气味，当从包装中取出该系统并在其使用时，特别会被察觉到。
在一般2至3年储藏期的过程中，由于部分分解，会发生这种气味明显加强，并且变成在主观上非常令人不愉快之类的气味。
WO95/08324 A1叙述至少两层的TTSs的制造方法，它是使用高挥发性的成分作为专有的溶剂。这些TTSs可含有不同的活性剂，包括烟碱、以及特别是薄荷醇、或其他的挥发性萜衍生物作为皮肤渗透增进剂。已叙述到在含烟碱的TTSs中的这些添加物，对气味方面没有特别的作用。关于“挥发性的萜衍生物”，在单萜醇类以及单萜酮类之间并没有区别。
EP 0 356 382 A2揭示基于某些嵌段共聚物的TTSs，其中也可使用烟碱作为活性剂。为了改进皮肤渗透性，提出了桉叶油素或桉树油类，特别强调以桉树脑为主要的组份；没有考虑薄荷油类的原料。在包含烟碱的贴片的令人不愉快气味方面，同样地未被考虑。
美国专利US 5 599 554 A是关于经粘液或经皮使用的烟碱，其中所使用的组合物也可包含芳香的物质或香料。所提及的有烟碱的特征气味是真的，但是其未被叙述为一种缺点。芳香族化合物，例如：薄荷醇或桉叶油素，被提及作为可选择的原料，但不是必要的薄荷油类或萜酮类。没有指出那些添加物的功能。可能其作为在口服施用中改进味道。
美国专利US 5 593 684 A叙述一种基于同时经粘液及经皮施用的烟碱的治疗的方法。在此，含有萜的植物分泌物在口服片剂中被用作“醚性油类”，以掩盖烟碱的令人不悦的气味。
美国专利US 4 933 184是关于已改进的经皮传送活性物质的TTSs，特别是用于烟碱的，而薄荷醇被用做增强剂；没有提及存在于薄荷类的醚性油类的其他物质，例如：单萜酮。薄荷油被用作增强剂，作为薄荷醇的替代物，但是令人惊奇的是没有产生该效果。对于其它的，这出版物只是关于活性物质渗透的改进，而不是涉及改进TTSs气味的方法。
因此，在含烟碱的TTSs的本发明目的，是根据权利要求1的介绍部分，通过添加适当的芳香物质，以中和这一特征性气味、或以更令人愉快的气味来掩盖之。
现在已发现的解决方法，是添加不同薄荷物种或其组份的精油类，特别是单萜酮类。根据本发明，这些添加物可用来掩盖或改进包含烟碱的TTSs的令人不悦气味。根据本发明的TTSs具有萃自薄荷物种的至少一种精油、或存在于这些精油类中的单萜酮的含量。
不同薄荷物种的精油类的组分，是以萜的代谢的产物为主，更精确的是以单萜类为主。
通常薄荷油的特征是其令人愉快的新鲜气味。所用的油类的实例为洋薄荷(peppermint)油、留兰香油或欧洲胡薄荷(poleimin)油，每一种都是萃自不同的植物。包含于这些油类的独特单萜类，可被分为单萜醇类及单萜酮类。
一般，单萜醇类为：薄荷醇、异薄荷醇、新薄荷醇、新异薄荷醇、及异长叶薄荷醇。一般的单萜酮类为薄荷酮、异薄荷酮、香芹酮、胡椒酮、长叶薄荷酮及异长叶薄荷酮。实际上，所有的这些代表物都是以对映异构体存在，都有光学上左旋及右旋的两种形式。
作为这组的代表物检测的有洋薄荷(Oleum Menthae peperitae)、留兰香(Oleum Menthae crispae)及(日本)薄荷(Oleum Menthae arvensis)的精油类。
洋薄荷油且特别是薄荷油，是以单萜醇类为主，特别是薄荷醇。相对地，留兰香油，包含上述所有的单萜酮类，特别是香芹酮(参照：在1997年版的欧洲药典中的论文“Pfefferminzol”[洋薄荷油])；在1997年版的德国药典中的论文“Minzol”[薄荷油]；以及G.施耐德(Schneider)在1998处所著的第2版Pharmazeutische Biologie[医药生物学]，BI学术出版社[BIWissenschaftsverlag]343-345页)。
做为单一物质，(-)-薄荷醇以及(-)-薄荷酮分别被做为一般的单萜醇及一般的单萜酮来测试。
实施例：
为了检验这种添加物的效果，设计出简化气味测试的模式。
烟碱以7％重量浓度与miglyol 812混合。Miglyol 812是一种饱和的三酸甘油酯，用作一种无气味的载体。7％重量浓度的烟碱相对应于在TTSs中所使用活性物质浓度约5-10％重量。对miglyol中的烟碱而言，造成与TTSs可比较的蒸气压以及因此类似强度的气味。在这测试混合物中添加5个测试物质或测试混合物：
(-)-薄荷醇、(-)-薄荷酮、洋薄荷油(根据欧洲药典的品质)、留兰香油(根据Deutscher Arzneimittel Codex DAC[德国医药法典]的品质)以及薄荷油(根据德国药典的品质)。
在每一个情况下所添加的量是0.5、1.0以及2.0％重量的份量。
产生了15个测试样品。另外，有一个样品的制备是没有气味改进添加物的。
这16个样品以6个人员来评估气味，各别添加物的种类以及量对该人员不是已知的。
评估的标准及等级数包含：
1.烟碱气味：感觉不到(4)；微弱(3)；中等(2)；明显(1)
2.整体的印象：令人不悦(1)；中等(2)；令人愉快(3)；有香味(4)
在将每一个样品及人员的两个数值相加之前，整体印象的评估是乘以因数2，用来更强调针对烟碱的气味。较高的数值代表较良好的评估。所用的等级数字用来形成平均值。理论的最小值是3.0，且理论最大值是12.0。
结果显示于表1中：
| 测试的产品/份量 | 0.5％重量 | 1.0％重量 | 2.0％重量 |
| (-)-薄荷醇 | 4.0 | 4.1 | 4.9 |
| (-)-薄荷酮 | 6.6 | 6.4 | 8.6 |
| 洋薄荷油 | 6.9 | 8.7 | 9.3 |
| 留兰香油 | 7.3 | 7.7 | 9.6 |
| 薄荷油 | 6.0 | 7.0 | 9.0 |
没有添加物的产品产生的值为4.0。
结果的图示列于图1中。
这表示薄荷酮超过薄荷醇的非常令人惊讶的清楚优点。与一般包含高至32％的薄荷酮(1997年的欧洲药典)的洋薄荷油比较，以薄荷醇为主(G.施耐德[Schneider]在1998年所著的第2版的医药生物学[PharmazeutischeBiologie]，BI学术出版社[BI Wissenschaftsverlag]，第345页)的薄荷油的较差的结果，是这些发现的支持证据。
最后，以香芹酮为主、并且实际上没有薄荷醇的留兰香油，产生最佳的结果。
总之，这说明单萜酮类、或单萜醇类与单萜酮类的混合物，超过纯单萜醇类的一个清楚优点。
因为该物质的高挥发性，根据本发明对含有烟碱的TTSs添加该物质的实际实施，具有某些困难；然而，这些困难可以参照PCT/WO 95 08324的介绍而排除。
根据本发明，在气味改进的TTSs的包含烟碱基质中，所含的单萜酮(类)或其精油的量是0.1至5.0％重量，优选为0.5至2％重量的量。
因此根据本发明，将物质添加到含有烟碱的TTSs中，造成一种有用的方式，用来改进这种TTSs的令人不悦的气味。
如权利要求1中介绍部分中所叙述的，该TTSs具有的特性是如上面所提及的，含有至少一种萃自薄荷物种中的精油、或存在于这些精油类的单萜酮。
优选地，单萜酮可以得自香芹酮、二氢基香芹酮、薄荷酮、异长叶薄荷酮、异薄荷酮、新薄荷酮、新异薄荷酮、或洋薄荷酮中之一。单萜酮类可以以纯的对映异构体或其混合物使用。
作为精油，特佳的是使用留兰香油(Oleum Menthae crispae)。
在含有尼古丁的基质中，单萜酮(类)或其精油类的含量优选是0.1至5％重量，特别是0.5至2％重量。
本发明还关于经皮治疗系统中掩盖由烟碱含量所引起的令人不悦气味的方法，这方法的特征在于添加至少一种气味改进物质到含有烟碱的经皮治疗系统，该物质是一种萃自薄荷物种的精油、或包含于萃自薄荷物种的精油中的单萜酮。
在此，优选地，上面所提及的单萜酮或洋薄荷油可被分别以单萜酮类或精油使用，其可以以纯的对映异构体或其混合物来使用。
含有烟碱基质中的单萜酮(类)或精油(类)，优选使用的浓度是0.1至5.0％重量，特别优选的浓度是0.5至2％重量。
另外，本发明包含萃自薄荷物种的精油、和/或包含于萃自薄荷物种的精油中的单萜酮，用以掩盖经皮治疗系统中的令人不悦的气味，该气味是由该经皮治疗系统中的烟碱的含量所引起的。
优选地，所使用的单萜酮是得自香芹酮、二氢基香芹酮、薄荷酮、异长叶薄荷酮、异薄荷酮、新薄荷酮、新异薄荷酮、或洋薄荷酮中之一，其可以以纯的对映异构体或其混合物。
做为精油，特别优选的是使用洋薄荷油(Oleum Menthae crispae)。
根据本发明，在使用用来掩盖含有烟碱的经皮治疗系统的令人不悦气味时，将单萜酮(类)或精油添加到含有烟碱的基质中，加入量优选的浓度为0.1至5.0％重量比，特别优选的浓度为0.5至2％重量。
Claims (13)
1.一种经皮治疗系统，具有一个背层、至少一个含有尼古丁层或矿物区域，其可具有压敏的粘着性质，以及一个可移除的保护层，其特征在于，含有至少一种萃自薄荷物种中的精油，或至少一种包含于这些精油类中的单萜酮。
2.根据权利要求1的经皮治疗系统，其特征在于，该单萜酮是选自香芹酮、二氢基香芹酮、薄荷酮、异长叶薄荷酮、异薄荷酮、新薄荷酮、新异薄荷酮、或洋薄荷酮中之一。
3.根据权利要求2的经皮治疗系统，其特征在于，该单萜酮是以纯的对映异构体或其混合物而使用。
4.根据权利要求1的经皮治疗系统，其特征在于，该精油是留兰香油(Oleum Menthae crispae)。
5.根据权利要求之一或以上的经皮治疗系统，其特征在于，在含烟碱的基质中的单萜酮(类)的含量为0.1至5.0％重量，优选为0.5至2％重量。
6.用来掩盖由烟碱含量所引起的经皮治疗系统的令人不悦气味的方法，其特征在于，添加至少一种气味改进物质至含有烟碱的经皮治疗系统中，该物质是一种萃自薄荷物种中的精油、或包含于萃自薄荷物种中的精油中的一种单萜酮。
7.根据权利要求6的方法，其特征在于，该精油是洋薄荷油(OleumMenthae crispae)。
8.根据权利要求6的方法，其特征在于，该单萜酮是得自香芹酮、二氢基香芹酮、薄荷酮、异长叶薄荷酮、异薄荷酮、新薄荷酮、新异薄荷酮、或洋薄荷酮中之一。
9.根据权利要求8的方法，其特征在于将该单萜酮(类)添加到含有烟碱的基质中，优选的浓度为0.1至5.0％重量，特别优选的浓度为0.5至2％重量。
10.一种萃自薄荷物种中的精油及或包含于萃自薄荷物种中的精油中的一种单萜酮的用途，其是用以掩盖经皮治疗系统的令人不悦的气味，该气味由该经皮治疗系统中的烟碱含量所引起。
11.根据权利要求10的用途，其特征在于，该单萜酮是得自香芹酮、二氢基香芹酮、薄荷酮、异长叶薄荷酮、异薄荷酮、新薄荷酮、新异薄荷酮、或洋薄荷酮中之一。
12.根据权利要求11的用途，其特征在于，将该单萜酮(类)添加到含有烟碱的基质中，优选的浓度为0.1至5.0％重量，特别优选的浓度为0.5至2％重量。
13.根据权利要求10的用途，其特征在于，该精油是洋薄荷油(OleumMenthae crispae)。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19913732.3 | 1999-03-26 | ||
| DE19913732A DE19913732A1 (de) | 1999-03-26 | 1999-03-26 | Nikotin-TTS mit einem Zusatz von Monoterpenketonen |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1345213A true CN1345213A (zh) | 2002-04-17 |
| CN1199623C CN1199623C (zh) | 2005-05-04 |
Family
ID=7902491
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB008055254A Expired - Lifetime CN1199623C (zh) | 1999-03-26 | 2000-03-21 | 具有烟碱并添加单萜酮的经皮治疗系统 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7029692B1 (zh) |
| EP (1) | EP1164996B1 (zh) |
| JP (1) | JP4750282B2 (zh) |
| KR (1) | KR100597802B1 (zh) |
| CN (1) | CN1199623C (zh) |
| AR (1) | AR027485A1 (zh) |
| AT (1) | ATE252356T1 (zh) |
| AU (1) | AU769656B2 (zh) |
| BR (1) | BR0010515A (zh) |
| CA (1) | CA2367615C (zh) |
| CZ (1) | CZ300409B6 (zh) |
| DE (2) | DE19913732A1 (zh) |
| DK (1) | DK1164996T3 (zh) |
| ES (1) | ES2211523T3 (zh) |
| HU (1) | HUP0200189A3 (zh) |
| IL (1) | IL145502A0 (zh) |
| NZ (1) | NZ514423A (zh) |
| PT (1) | PT1164996E (zh) |
| RU (1) | RU2228740C2 (zh) |
| TR (1) | TR200102605T2 (zh) |
| TW (1) | TWI227666B (zh) |
| WO (1) | WO2000057824A1 (zh) |
| ZA (1) | ZA200107864B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264277B (zh) * | 2008-04-16 | 2012-09-26 | 冯冲 | 一种控烟戒烟复方精油 |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7198801B2 (en) * | 2000-08-03 | 2007-04-03 | Antares Pharma Ipl Ag | Formulations for transdermal or transmucosal application |
| US8980290B2 (en) | 2000-08-03 | 2015-03-17 | Antares Pharma Ipl Ag | Transdermal compositions for anticholinergic agents |
| ATE355854T1 (de) * | 2000-08-03 | 2007-03-15 | Antares Pharma Ipl Ag | Neue zusammensetzung zur transdermalen und/oder transmukosalen wirkstoffanwendung mit geeignetem therapeutischen spiegel |
| US20070225379A1 (en) * | 2001-08-03 | 2007-09-27 | Carrara Dario Norberto R | Transdermal delivery of systemically active central nervous system drugs |
| EP1670433B1 (en) * | 2003-10-10 | 2011-11-23 | Antares Pharma IPL AG | Transdermal pharmaceutical formulation for minimizing skin residues |
| US7387788B1 (en) | 2003-10-10 | 2008-06-17 | Antares Pharma Ipl Ag | Pharmaceutical compositions of nicotine and methods of use thereof |
| WO2007124250A2 (en) * | 2006-04-21 | 2007-11-01 | Antares Pharma Ipl Ag | Methods of treating hot flashes with formulations for transdermal or transmucosal application |
| WO2006125642A1 (en) * | 2005-05-27 | 2006-11-30 | Antares Pharma Ipl Ag | Methods and apparatus for transdermal or transmucosal application of testosterone |
| KR100699582B1 (ko) | 2005-07-11 | 2007-03-23 | 삼성전기주식회사 | 출력 버퍼회로 |
| DE102005033543A1 (de) * | 2005-07-14 | 2007-01-18 | Grünenthal GmbH | Ein einen Duftstoff aufweisendes transdermales therapeutisches System |
| IL177071A0 (en) * | 2005-08-01 | 2006-12-10 | Nitto Denko Corp | Method of preparing a nicotine transdermal preparation |
| ES2499067T3 (es) | 2005-10-13 | 2014-09-26 | Nitto Denko Corporation | Preparación transdérmica de nicotina y método de producción de la misma |
| WO2008067991A2 (en) * | 2006-12-08 | 2008-06-12 | Antares Pharma Ipl Ag | Skin-friendly drug complexes for transdermal administration |
| RU2573293C2 (ru) * | 2010-03-26 | 2016-01-20 | Филип Моррис Продактс С.А. | Ингибирование раздражающих ощущений при потреблении некурительных табачных продуктов |
| JP5730355B2 (ja) * | 2013-07-24 | 2015-06-10 | 学校法人近畿大学 | Ｃｙｐ２ａ１３阻害剤 |
| JP6888974B2 (ja) * | 2016-01-27 | 2021-06-18 | 学校法人近畿大学 | Ｃｙｐ２ａ１３阻害活性を有する化合物及びｃｙｐ２ａ１３阻害剤 |
| WO2019055880A2 (en) | 2017-09-15 | 2019-03-21 | Ampersand Biopharmaceuticals, Inc. | METHOD OF ADMINISTRATION AND TREATMENT |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3559655A (en) * | 1969-02-25 | 1971-02-02 | Sutton Res Corp | Oxidized cellulose substitute smoking material and method of making same |
| US4039653A (en) * | 1974-01-23 | 1977-08-02 | Defoney, Brenman, Mayes & Baron | Long-acting articles for oral delivery and process |
| US4933184A (en) * | 1983-12-22 | 1990-06-12 | American Home Products Corp. (Del) | Menthol enhancement of transdermal drug delivery |
| JPH01157921A (ja) * | 1987-12-15 | 1989-06-21 | Tsumura & Co | 二重盲検試験用製剤の製造方法 |
| JPH01290608A (ja) * | 1988-05-18 | 1989-11-22 | Sunstar Inc | 殺菌剤組成物 |
| EP0356382B1 (de) * | 1988-08-02 | 1994-02-16 | Ciba-Geigy Ag | Mehrschichtiges Pflaster |
| JP2905210B2 (ja) * | 1989-01-23 | 1999-06-14 | フロイント産業株式会社 | 経皮、経粘膜吸収促進剤および経皮、経粘膜製剤 |
| JPH0748190B2 (ja) * | 1990-01-22 | 1995-05-24 | 株式会社東芝 | キャッシュメモリ内蔵マイクロプロセッサ |
| JPH0679002A (ja) * | 1993-12-14 | 1994-03-22 | Hisamitsu Pharmaceut Co Inc | 経皮投与用パッチシステム |
| JPH06181972A (ja) * | 1992-12-18 | 1994-07-05 | Kanebo Ltd | 煙草臭消臭剤 |
| US5520924A (en) * | 1993-07-09 | 1996-05-28 | Mizu Systems Corporation | Methods and articles for administering drug to the oral cavity |
| US5362496A (en) * | 1993-08-04 | 1994-11-08 | Pharmetrix Corporation | Method and therapeutic system for smoking cessation |
| DE4332094C2 (de) * | 1993-09-22 | 1995-09-07 | Lohmann Therapie Syst Lts | Lösemittelfrei herstellbares Wirkstoffpflaster und Verfahren zu seiner Herstellung |
| JPH07133490A (ja) * | 1993-11-10 | 1995-05-23 | Pola Chem Ind Inc | 消臭剤 |
| AU2703795A (en) * | 1994-06-23 | 1996-01-19 | Procter & Gamble Company, The | Treatment of nicotine craving and/or smoking withdrawal symptoms with a transdermal or transmucosal composition containing nicotine and caffeine or xanthine |
| JPH09110680A (ja) * | 1995-10-19 | 1997-04-28 | Yuutoku Yakuhin Kogyo Kk | 皮膚炎治療貼付剤 |
| JPH10130118A (ja) * | 1996-10-25 | 1998-05-19 | Lion Corp | 外用剤組成物 |
| JPH10306030A (ja) * | 1997-05-07 | 1998-11-17 | Taisho Pharmaceut Co Ltd | 外用剤組成物 |
-
1999
- 1999-03-26 DE DE19913732A patent/DE19913732A1/de not_active Withdrawn
-
2000
- 2000-03-21 AU AU38134/00A patent/AU769656B2/en not_active Expired
- 2000-03-21 CA CA002367615A patent/CA2367615C/en not_active Expired - Lifetime
- 2000-03-21 BR BR0010515-5A patent/BR0010515A/pt not_active IP Right Cessation
- 2000-03-21 NZ NZ514423A patent/NZ514423A/en not_active IP Right Cessation
- 2000-03-21 PT PT00916981T patent/PT1164996E/pt unknown
- 2000-03-21 WO PCT/EP2000/002457 patent/WO2000057824A1/de active IP Right Grant
- 2000-03-21 CN CNB008055254A patent/CN1199623C/zh not_active Expired - Lifetime
- 2000-03-21 IL IL14550200A patent/IL145502A0/xx not_active IP Right Cessation
- 2000-03-21 TR TR2001/02605T patent/TR200102605T2/xx unknown
- 2000-03-21 EP EP00916981A patent/EP1164996B1/de not_active Expired - Lifetime
- 2000-03-21 HU HU0200189A patent/HUP0200189A3/hu unknown
- 2000-03-21 JP JP2000607578A patent/JP4750282B2/ja not_active Expired - Lifetime
- 2000-03-21 DE DE50004156T patent/DE50004156D1/de not_active Expired - Lifetime
- 2000-03-21 CZ CZ20013457A patent/CZ300409B6/cs not_active IP Right Cessation
- 2000-03-21 US US09/937,534 patent/US7029692B1/en not_active Expired - Lifetime
- 2000-03-21 ES ES00916981T patent/ES2211523T3/es not_active Expired - Lifetime
- 2000-03-21 AT AT00916981T patent/ATE252356T1/de active
- 2000-03-21 KR KR1020017012169A patent/KR100597802B1/ko active IP Right Grant
- 2000-03-21 RU RU2001125674/15A patent/RU2228740C2/ru active
- 2000-03-21 DK DK00916981T patent/DK1164996T3/da active
- 2000-03-24 TW TW089105397A patent/TWI227666B/zh not_active IP Right Cessation
- 2000-03-24 AR ARP000101319A patent/AR027485A1/es active IP Right Grant
-
2001
- 2001-09-25 ZA ZA200107864A patent/ZA200107864B/xx unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264277B (zh) * | 2008-04-16 | 2012-09-26 | 冯冲 | 一种控烟戒烟复方精油 |
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0200189A2 (hu) | 2002-05-29 |
| TWI227666B (en) | 2005-02-11 |
| CZ20013457A3 (cs) | 2002-03-13 |
| PL351313A1 (en) | 2003-04-07 |
| CA2367615C (en) | 2009-10-13 |
| DK1164996T3 (da) | 2004-02-16 |
| KR20010112366A (ko) | 2001-12-20 |
| JP4750282B2 (ja) | 2011-08-17 |
| DE50004156D1 (de) | 2003-11-27 |
| ATE252356T1 (de) | 2003-11-15 |
| PT1164996E (pt) | 2004-03-31 |
| DE19913732A1 (de) | 2000-09-28 |
| NZ514423A (en) | 2003-08-29 |
| TR200102605T2 (tr) | 2002-01-21 |
| BR0010515A (pt) | 2003-07-22 |
| WO2000057824A1 (de) | 2000-10-05 |
| AU3813400A (en) | 2000-10-16 |
| EP1164996A1 (de) | 2002-01-02 |
| AR027485A1 (es) | 2003-04-02 |
| AU769656B2 (en) | 2004-01-29 |
| KR100597802B1 (ko) | 2006-07-10 |
| CA2367615A1 (en) | 2000-10-05 |
| ZA200107864B (en) | 2002-11-27 |
| CN1199623C (zh) | 2005-05-04 |
| CZ300409B6 (cs) | 2009-05-13 |
| RU2228740C2 (ru) | 2004-05-20 |
| HUP0200189A3 (en) | 2011-02-28 |
| JP2002540125A (ja) | 2002-11-26 |
| US7029692B1 (en) | 2006-04-18 |
| EP1164996B1 (de) | 2003-10-22 |
| ES2211523T3 (es) | 2004-07-16 |
| IL145502A0 (en) | 2002-06-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1199623C (zh) | 具有烟碱并添加单萜酮的经皮治疗系统 | |
| Bersan et al. | Action of essential oils from Brazilian native and exotic medicinal species on oral biofilms | |
| US5665386A (en) | Use of essential oils to increase bioavailability of oral pharmaceutical compounds | |
| CA2272540C (en) | Anti-oxidizing composition for scavenging free radicals, pharmaceutical composition comprising the same, and process for preparing the same | |
| EP2207546A1 (en) | Antifungal treatment of nails | |
| DE3901368A1 (de) | Mittel zur vorbeugung gegen und behandlung von parodontopathien | |
| Shamseddine et al. | Composition’s effect of Origanum Syriacum essential oils in the antimicrobial activities for the treatment of denture stomatitis | |
| DE102005050654A1 (de) | Lippenpflaster | |
| CN109529086A (zh) | 一种多功能纳米除臭杀菌负离子添加剂及其制备方法 | |
| EP1200070A1 (de) | Ambroxolhaltige lutschtablette | |
| Schmitt et al. | Variation of in vitro human skin permeation of rose oil between different application sites | |
| CN113143995A (zh) | 一种大麻提取物舌下片及其制备工艺和应用 | |
| KR100558015B1 (ko) | 사자발쑥 정유를 함유한 치아우식증 원인균의 항균활성 조성물 | |
| JPS6330424A (ja) | 白癬菌治療剤 | |
| MXPA01009198A (en) | Transdermal therapeutic system with nicotine and addition of monoterpene ketones | |
| Garcia Pinto et al. | Effect of limonene associated with bioactive glass‐ceramic on dentin/adhesive interface | |
| WO2022180077A1 (de) | Mittel zum binden und verdrängen von corona-viren auf lebenden zellen und auf oberflächen | |
| CN1479623A (zh) | 萎叶的叶提取物的抗单核细胞活性 | |
| DE60216518T2 (de) | Bioaktive hexan fraktion aus vetiveria zizanioides | |
| EP0804206B1 (fr) | Composition antifongique contenant du crotamiton et de d'aldehyde salicylique | |
| WO2004069231A1 (de) | Transdermales therapeutisches system mit verbessertem hautklebeverhalten | |
| Dahl et al. | 96. Bronchodilators in asthma and COPD | |
| PL203564B1 (pl) | Transdermalny system terapeutyczny zawieraj acy nikotyn e, sposób neutralizacji jego nieprzyjemnego zapachu oraz zastosowanie olejku eterycznego i/lub ketonu monoterpenowego | |
| DE2205986B2 (de) | Presspapier-testblaettchen fuer mikrobiologische untersuchungen | |
| EP1875942A1 (de) | Riechstoffhaltige Zusammensetzungen umfassend deliqueszente Stoffe |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CX01 | Expiry of patent term |
Granted publication date: 20050504 |
|
| CX01 | Expiry of patent term |