WO2001026687A1 - Compositions d'electroporation - Google Patents
Compositions d'electroporation Download PDFInfo
- Publication number
- WO2001026687A1 WO2001026687A1 PCT/JP2000/002243 JP0002243W WO0126687A1 WO 2001026687 A1 WO2001026687 A1 WO 2001026687A1 JP 0002243 W JP0002243 W JP 0002243W WO 0126687 A1 WO0126687 A1 WO 0126687A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- electroporation
- present
- weight
- osmotic pressure
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
Definitions
- the present invention relates to a composition for electroporation useful for enhancing transdermal absorption of a drug or the like.
- the present invention is useful in the field of medicine. Obedience
- the percutaneous absorption route is less prone to pain than injections, and is less likely to be forgotten than oral administration. Vulnerable to the protection function, there is considerable difficulty in percutaneous absorption, and at present it has not been established as a drug delivery method.
- a so-called electoral poration in which a voltage is applied to create a pore in the skin structure, and a drug is transported through the pore, is exemplified.
- electroporation it has recently been revealed that the behavior of the drug is different from that of ordinary administration, and development of a composition for transdermal administration suitable for such an electoral port has been developed.
- electroporation is a useful means for transdermal drug delivery, drug delivery alone may not be sufficient in some cases, and there has been a demand for a formulation that enhances this effect.
- the present inventors have conducted intensive research efforts to find a composition for transdermal administration suitable for elect-oral poration to improve the transdermal permeability of drugs.
- a formulation can be achieved by adjusting the electrolyte concentration to an osmotic pressure lower than the physiological osmotic pressure, and completed the invention.
- the addition of monoterpenes and polyvalent alcohols could further improve such permeability, and developed the invention.
- the present invention provides a composition for electroporation in which the electrolyte concentration is adjusted to an osmotic pressure lower than a physiological osmotic pressure.
- the present invention provides a composition for election port poisoning, which preferably contains a monoterpene or a polyhydric alcohol.
- composition for electroporation of the present invention is characterized in that its osmotic pressure is lower than physiological osmotic pressure. That is, in physiological saline, the osmotic pressure is adjusted to be equal to the physiological osmotic pressure by adding 0.9% of sodium chloride as an electrolyte.
- the poration is characterized by being adjusted lower. That is, it is characterized in that the substantial content of the electrolyte including the active ingredient is not more than the chemical equivalent of sodium chloride in physiological saline.
- substantially means the concentration of the electrolyte, and thus takes into account the dissociation constant. In other words, those with a small dissociation constant may be included as much.
- the level of osmotic pressure can be determined by using a semi-permeable membrane such as cellophane, depending on whether the osmotic pressure is lower or higher than that of physiological saline.
- a semi-permeable membrane such as cellophane
- the transdermal permeability of the drug can be further enhanced by utilizing osmotic pressure in addition to election poration.
- limiting the amount of electrolyte is advantageous in this sense, since it limits the effect of closing the pores created by electroporation of the electrolyte. Therefore, the most preferred form is a form containing no electrolyte other than the active ingredient.
- the composition for electroporation of the present invention is characterized by preferably containing a polyhydric alcohol.
- a polyhydric alcohol that can be used in the composition for electroporation of the present invention, any polyhydric alcohol that is usually used in an approximate field such as an external preparation for skin can be used without particular limitation.
- Preferred examples thereof include polyethylene glycol, 1,3-butanediol, propylene glycol, glycerin, dipropylene glycol, diglycerin, sorbitol, and maltitol.
- propylene glycol is preferred.
- Glycerin, polyethylene glycol and 1,3-butanediol are preferred. These are preferably liquid at 25 ° C.
- the polyhydric alcohol is composed of only this. This is because it is an excellent ingredient for electoral poration, especially for enhancing skin absorption, and has been used in many external pharmaceutical preparations for skin, and its safety properties have already been grasped. Because there is.
- the content of these polyhydric alcohols is preferably 1 to 90% by weight, more preferably 5 to 30% by weight. This is a value in view of the safety of polyhydric alcohol, the degree of freedom of selection of arbitrary components in the composition of the composition, the effective amount of the medicinal component, and the optimal amount of the skin absorption promoting action.
- the composition for election port poration of the present invention preferably further contains a monoterpene.
- the monoterpene include menthol and its optical isomers, menthol, timole, and the like. Among these, menthol is preferred, and menthol is more preferred. This is because menthols, especially 1-menthol, are excellent in percutaneous absorption promoting action especially in electroporation among monoterpenes.
- the preferred content of monoterpenes in the composition for electroplating of the present invention is 0.1 to 10% by weight, more preferably 0.5 to 5% by weight. This is because if the amount of monoterpenes is too high, irritation may occur, and if the amount is too low, the effect of promoting skin absorption cannot be obtained. It is because there is a case.
- composition for election portion of the present invention may be used in the composition for election portion usually except for polyhydric alcohols and monoterpenes which are preferable components within a range satisfying the above essential conditions. It can contain optional ingredients for the formulation to be performed. Such optional components include, for example, hydrocarbons such as squalane, petrolatum, and microcrystalline phosphorus wax, jojoba oil, carnauba wax, esters such as octyldodecyl oleate, olive oil, tallow, coconut oil and the like.
- hydrocarbons such as squalane, petrolatum, and microcrystalline phosphorus wax
- jojoba oil such as jojoba oil, carnauba wax
- esters such as octyldodecyl oleate, olive oil, tallow, coconut oil and the like.
- Triglycerides such as oils, fatty acids such as stearic acid, oleic acid and ritinoleic acid, higher alcohols such as oleyl alcohol, stearyl alcohol, octyldodecanol, and sulfo succinate esters and sodium polyoxyethylene alkyl sulfate.
- Anionic surfactants amphoteric surfactants such as alkyl betaine salts, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, their polyoxyethylene adducts, polyoxyethylene Alkyle Le, non Ion surfactants such as poly O key Chez Ji Ren fatty acid esters, thickening-gelling agents, antioxidants, ultraviolet absorbers, coloring materials, preservatives, powders and the like can be preferably exemplified.
- the drug to be transdermally administered by such electoral poration can be applied without any particular limitation as long as it is usually used as a pharmaceutical.
- codin codin, morphine, hide-orthomorphone , Oxycodone, pethidine, bufrenorphine hydrochloride, pentazine, tramadol hydrochloride, etc.
- analgesic and anti-inflammatory drugs insulin, calcitonin, elcatonin, adrenocorticotropic hormone (ACTH), parathyroid hormone (PTH), selectin, oxyxin, angiotine Tensin,?
- -Endorphin vasobresin, glucagon, somatosustin, luteinizing hormone-releasing hormone (LH-RH), enkephalin, neurotensin, atrial sodium diuretic peptide (ANP;), growth hormone, bradykinin, substance P, Dainorf Thyroid, thyroid stimulating hormone, (TSH), prolactin, G-CSF, glutathione peroxidase, peroxydide dismutase (SOD), desmopressin, somatomedin, melanocyte stimulating hormone (MSH), calcitonin gene-related ⁇ Protein drugs such as butyl (CGRP), endothelin, thyrotropin releasing hormone (TRH), 5 Interleukins, interferons, antiplatelet agents, vasodilators, argato-oral pan, which is an anti-atherosclerotic agent, sarpogrelate hydrochloride, berabrostonalolidium, limapro
- the composition for electroporation of the present invention is prepared by treating the above essential components, preferred components, optional components and active ingredients according to a conventional method to adjust the physical properties of the active ingredients, etc., into a solution dosage form, an emulsifier. Processed into dosage forms such as solid, semi-solid dosage forms, and solid dosage forms, and used for electoral poration. That is, by using the composition of the present invention, the drug of the active ingredient can be transdermally administered by electroporation. For election port polish, use with the device for electoral port polish.
- preferred dosage forms include aqueous dosage forms, and particularly preferred examples include aqueous solution dosage forms, aqueous gel dosage forms, and emulsified dosage forms.
- the external medicine administration unit for skin of the present invention is obtained by combining the above-described composition for electroporation of the present invention with a device for electroporation.
- Electroporation devices are not particularly limited as long as they are normally used for such purposes.
- the devices described in Table 10-502827, JP-T-1111503503, JP-T 08-51 1680, JP-T 03-502416 may be used.
- commercially available devices for such electoral port por- tions include devices such as £ CM-600 manufactured by 8 companies and GENE PULSER manufactured by BI0-RAD. These devices are used. It is also possible.
- Fig. 1 is a diagram showing a device of an election port polish according to a second embodiment.
- BEST MODE FOR CARRYING OUT THE INVENTION the present invention will be described in more detail with reference to examples, but it is needless to say that the present invention is not limited only to these examples.
- a composition for election port poration of the present invention was prepared.
- As a model labeling drug 1 mM sodium lucosein was used. These were stirred and solubilized to give a composition (liquid) for election portionation of the present invention.
- the percutaneous penetration test using Franz cells was used to measure the percutaneous absorption of these compositions for elect-portion polish. That is, a skin specimen 2 from the abdomen of the hairless rat was taken from the abdomen of the hairless rat, and the horny layer was attached to the donor side as a septum, and a saline solution was placed on one side of the receiver. 3, and the donor side was filled with 3 mL of the composition 4 for electrophoresis of the present invention.
- the pulse voltage generator 7 uses BI 0-RAD GENE PULSER, 300 V capacitor with 25 ⁇ F, and the first 5 minutes out of 60 minutes. A pulse (0.5 minute interval) was applied, and the voltage was turned off for the remaining 55 minutes.
- Table 1 the accumulated permeation amount (nmol / cm2) for 6 hours. This indicates that the transdermal permeability is enhanced when the osmotic pressure of the composition is within the range of physiological osmotic pressure or lower. This device is shown in Fig. 1. table 1
- the concentration of propylene glycol was varied to prepare a composition (solution) for electoral poration of the present invention. That is, the formulation components were stirred and solubilized to obtain a composition. The cumulative permeation amount for 1 to 3 hours was measured in the same manner as in Examples 1 and 2. Table 2 shows the results. This indicates that the polyhydric alcohol has an optimum concentration, and the polyhydric alcohol content is preferably 5 to 30% by weight. Table 2
- Example 3 Sodium lucerin 1 mM 46.8 147.8 328.8 f. 11 lenk, 'recolor 10% by weight
- Example 6 Sodium lucerin 1 mM 9.1 27.0 0.36.2 F. Lenk ', Re:]-100% by weight
- a composition for electoral poration of the present invention was prepared. That is, the formulation components were stirred and solubilized to obtain a composition for election port poration.
- the cumulative drug permeation amount was 0.25.2 for 1 hour, 138.9 for 2 hours, and 388.8 for 3 hours, indicating that monoterpene is preferably contained.
- a composition for electroporation of the present invention was prepared. That is, the formulation components were stirred and solubilized to obtain a composition for election port poration.
- the cumulative drug permeation amount was 13.4 for 1 hour, 73.1 for 2 hours, and 179.7 for 3 hours, indicating that glycerin is also preferable as a polyhydric alcohol.
- composition for election port polish of the present invention was prepared. That is, the formulation components were stirred and solubilized to obtain a composition for election port poration.
- composition for electroporation of the present invention was prepared according to the following formulation (that is, the formulation components were solubilized by stirring to obtain a composition for electoral poration).
- Example 1 1> 30 parts by weight of propylene glycol
- a composition for electoral poration of the present invention was prepared. That is, the formulation components were stirred and solubilized to obtain a composition for election port poration.
- composition for electoral poration of the present invention was prepared. That is, the prescription ingredient I was added to the mouth, stirred, dispersed and solubilized to obtain a composition (emulsion) for elect-portion polishion.
- composition for transdermal administration suitable for election poration can be provided, and it is useful in the pharmaceutical field.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/110,712 US7197359B1 (en) | 1999-10-14 | 2000-04-06 | Compositions for electroporation |
EP00915387A EP1222930B1 (en) | 1999-10-14 | 2000-04-06 | Compositions for electroporation |
DE60031709T DE60031709T2 (de) | 1999-10-14 | 2000-04-06 | Zusammensetzungen für die elektroporation |
JP2001529748A JP4868678B2 (ja) | 1999-10-14 | 2000-04-06 | エレクトロポーレーション用の組成物 |
AU36720/00A AU3672000A (en) | 1999-10-14 | 2000-04-06 | Compositions for electroporation |
CA002387193A CA2387193C (en) | 1999-10-14 | 2000-04-06 | Compositions for electroporation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP29173399 | 1999-10-14 | ||
JP11/291733 | 1999-10-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001026687A1 true WO2001026687A1 (fr) | 2001-04-19 |
Family
ID=17772706
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2000/002243 WO2001026687A1 (fr) | 1999-10-14 | 2000-04-06 | Compositions d'electroporation |
Country Status (8)
Country | Link |
---|---|
US (1) | US7197359B1 (ja) |
EP (1) | EP1222930B1 (ja) |
JP (1) | JP4868678B2 (ja) |
AT (1) | ATE344055T1 (ja) |
AU (1) | AU3672000A (ja) |
CA (1) | CA2387193C (ja) |
DE (1) | DE60031709T2 (ja) |
WO (1) | WO2001026687A1 (ja) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6641591B1 (en) | 1999-08-26 | 2003-11-04 | John H. Shadduck | Instruments and techniques for controlled removal of epidermal layers |
US8048089B2 (en) | 2005-12-30 | 2011-11-01 | Edge Systems Corporation | Apparatus and methods for treating the skin |
US9566088B2 (en) | 2006-03-29 | 2017-02-14 | Edge Systems Llc | Devices, systems and methods for treating the skin |
US10172644B2 (en) | 2006-03-29 | 2019-01-08 | Edge Systems Llc | Devices, systems and methods for treating the skin |
EP2240099B1 (en) | 2008-01-04 | 2018-02-21 | Edge Systems LLC | Apparatus for treating the skin |
US9056193B2 (en) * | 2008-01-29 | 2015-06-16 | Edge Systems Llc | Apparatus and method for treating the skin |
EP2451367B1 (en) * | 2009-07-08 | 2020-01-22 | Edge Systems Corporation | Devices for treating the skin using time-release substances |
US10238812B2 (en) | 2013-03-15 | 2019-03-26 | Edge Systems Llc | Skin treatment systems and methods using needles |
EP3903704B1 (en) | 2013-03-15 | 2022-11-02 | HydraFacial LLC | Devices and systems for treating the skin |
EP3795204B1 (en) | 2014-12-23 | 2023-10-25 | HydraFacial LLC | Device for treating the skin using a rollerball |
US10179229B2 (en) | 2014-12-23 | 2019-01-15 | Edge Systems Llc | Devices and methods for treating the skin using a porous member |
US11241357B2 (en) | 2015-07-08 | 2022-02-08 | Edge Systems Llc | Devices, systems and methods for promoting hair growth |
WO2018064463A1 (en) * | 2016-09-30 | 2018-04-05 | University Of Florida Research Foundation, Inc. | Systems and methods including porous membrane for low-voltage continuous cell electroporation |
USD1016615S1 (en) | 2021-09-10 | 2024-03-05 | Hydrafacial Llc | Container for a skin treatment device |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989006555A1 (en) * | 1988-01-21 | 1989-07-27 | Massachusetts Institute Of Technology | Transport of molecules across tissue using electroporation |
WO1996033771A2 (en) * | 1995-04-28 | 1996-10-31 | Alza Corporation | Composition and method of enhancing electrotransport agent delivery |
JPH09255561A (ja) * | 1996-03-26 | 1997-09-30 | Hisamitsu Pharmaceut Co Inc | エレクトロポレーション用マイクロエマルション製剤 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
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US4933184A (en) | 1983-12-22 | 1990-06-12 | American Home Products Corp. (Del) | Menthol enhancement of transdermal drug delivery |
US5069908A (en) * | 1989-06-19 | 1991-12-03 | Henley International, Inc. | Crosslinked hydrogel and method for making same |
DE3925680A1 (de) * | 1989-08-03 | 1991-02-07 | Kruess Gmbh Wissenschaftliche | Verfahren zur herstellung vitaler wirkstoff-beladener humanerythrozyten |
GB8921710D0 (en) * | 1989-09-26 | 1989-11-08 | Mentholatum Co Ltd | Ibuprofen triturates and topical compositions containing same |
US5464386A (en) | 1992-08-17 | 1995-11-07 | Genetronics, Inc. | Transdermal drug delivery by electroincorporation of vesicles |
AU680890B2 (en) | 1993-03-23 | 1997-08-14 | Cbr Laboratories, Inc. | Method and apparatus for encapsulation of biologically-active substances in cells |
US5439440A (en) | 1993-04-01 | 1995-08-08 | Genetronics, Inc. | Electroporation system with voltage control feedback for clinical applications |
US5997501A (en) * | 1993-11-18 | 1999-12-07 | Elan Corporation, Plc | Intradermal drug delivery device |
US6176842B1 (en) * | 1995-03-08 | 2001-01-23 | Ekos Corporation | Ultrasound assembly for use with light activated drugs |
US5843014A (en) | 1995-03-24 | 1998-12-01 | Alza Corporation | Display for an electrotransport delivery device |
IT1285405B1 (it) | 1995-06-06 | 1998-06-03 | Alza Corp | Modificazione di farmaci polipeptidici per accrescere il flusso per elettrotrasporto. |
DE69630918T2 (de) * | 1995-06-09 | 2004-10-28 | Hisamitsu Pharmaceutical Co., Inc., Tosu | Matrix für Iontophorese |
ATE248004T1 (de) * | 1995-06-14 | 2003-09-15 | Hisamitsu Pharmaceutical Co | Schnittstelle für iontophorese |
US6266560B1 (en) * | 1998-06-19 | 2001-07-24 | Genetronics, Inc. | Electrically assisted transdermal method and apparatus for the treatment of erectile dysfunction |
EP1100579B1 (en) | 1998-07-13 | 2015-09-02 | Inovio Pharmaceuticals, Inc. | Skin and muscle-targeted gene therapy by pulsed electrical field |
JP2002520101A (ja) | 1998-07-13 | 2002-07-09 | ジェネトロニクス、インコーポレーテッド | 電気的に補助される化粧用薬剤の局部送達法および装置 |
DE69921489T2 (de) * | 1998-08-31 | 2005-10-27 | Johnson & Johnson Consumer Companies, Inc. | Elektrotransportvorrichtung mit klingen |
US6678558B1 (en) * | 1999-03-25 | 2004-01-13 | Genetronics, Inc. | Method and apparatus for reducing electroporation-mediated muscle reaction and pain response |
-
2000
- 2000-04-06 DE DE60031709T patent/DE60031709T2/de not_active Expired - Fee Related
- 2000-04-06 EP EP00915387A patent/EP1222930B1/en not_active Expired - Lifetime
- 2000-04-06 CA CA002387193A patent/CA2387193C/en not_active Expired - Fee Related
- 2000-04-06 AU AU36720/00A patent/AU3672000A/en not_active Abandoned
- 2000-04-06 JP JP2001529748A patent/JP4868678B2/ja not_active Expired - Fee Related
- 2000-04-06 WO PCT/JP2000/002243 patent/WO2001026687A1/ja active IP Right Grant
- 2000-04-06 US US10/110,712 patent/US7197359B1/en not_active Expired - Fee Related
- 2000-04-06 AT AT00915387T patent/ATE344055T1/de not_active IP Right Cessation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989006555A1 (en) * | 1988-01-21 | 1989-07-27 | Massachusetts Institute Of Technology | Transport of molecules across tissue using electroporation |
WO1996033771A2 (en) * | 1995-04-28 | 1996-10-31 | Alza Corporation | Composition and method of enhancing electrotransport agent delivery |
JPH09255561A (ja) * | 1996-03-26 | 1997-09-30 | Hisamitsu Pharmaceut Co Inc | エレクトロポレーション用マイクロエマルション製剤 |
Also Published As
Publication number | Publication date |
---|---|
JP4868678B2 (ja) | 2012-02-01 |
EP1222930B1 (en) | 2006-11-02 |
AU3672000A (en) | 2001-04-23 |
DE60031709T2 (de) | 2007-06-28 |
CA2387193C (en) | 2008-12-09 |
ATE344055T1 (de) | 2006-11-15 |
EP1222930A1 (en) | 2002-07-17 |
US7197359B1 (en) | 2007-03-27 |
DE60031709D1 (de) | 2006-12-14 |
EP1222930A4 (en) | 2005-03-02 |
CA2387193A1 (en) | 2001-04-19 |
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