WO2000072823A1 - Preparations for the application of anti-inflammatory agents - Google Patents
Preparations for the application of anti-inflammatory agents Download PDFInfo
- Publication number
- WO2000072823A1 WO2000072823A1 PCT/EP2000/004783 EP0004783W WO0072823A1 WO 2000072823 A1 WO2000072823 A1 WO 2000072823A1 EP 0004783 W EP0004783 W EP 0004783W WO 0072823 A1 WO0072823 A1 WO 0072823A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- preparation
- agent
- liposome
- agents
- process according
- Prior art date
Links
Classifications
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the invention concerns preparations for the application of agents with anti- inflammatory, especially antiseptic and/or wound healing promoting properties, to the interior of the human or animal body.
- the preparations are specifically applied to bones, organs, joints, muscle tissue, mucous membranes and mucosa-like unkeratinized epithelial tissues forming interior body parts of humans and animals.
- the invention concerns the prevention or treatment of infections in joints such as the knee, the hip joint, the shoulder joint and the elbow.
- the invention concerns a method of preventing or treating infections by applying a pharmaceutical preparation.
- antibiotic and antiseptic agents are known for the topical treatment of infectious maladies.
- a decisive disadvantage of antibiotic agents is that the infecting bacteria show primary resistances, and can acquire secondary resistances, against these agents. Further, antibiotics quite often lead to patient sensibilisation.
- the use of e.g. halogen-releasing antiseptics such as povidone iodine, also known as polyvidone iodine or PVP-iodine, i.e. the poly(l-vinyl-2- pyrrolidin-2-one)-iodine complex, can prevent resistances.
- Antiseptic agents are also much more rarely allergenic as compared to antibiotics.
- antibiotic and antiseptic agents are known for the topical treatment of infectious maladies.
- a decisive disadvantage of antibiotic agents is that the infecting bacteria show primary resistances, and can acquire secondary resistances, against these agents. Further, antibiotics quite often lead to patient sensibilisation.
- the use of e.g. halogen-relasing antiseptics such as povidone iodine, also known as polyvidone iodine or PVP iodine, i.e. the poly(l-vinyl-2-pyrrolidin-2- one)-iodine complex, can prevent resistances.
- Antiseptic agents are also much more rarely allergenic as compared to antibiotics.
- infectious diseases of the interior body parts are generally treated with antibiotics. This leads to the complications which are known to the skilled person. For example, patients suffering from chronical inflammation of joints, such as the knee or elbow, are often treated with antibiotics in order to alleviate the symptoms. However, this often merely leads to resistances of the bacteria which are responsible for the symptoms. Many diseases are caused by viruses and against these, antibiotics are not effective. Such patients are not cured from the infections.
- liposome preparations of PVP-iodine are shown therein to be topically applicable to the external parts of the eye. These preparations generally take the form of a cream, an ointment, a lotion, a gel or a drop formulation.
- Liposomes are well-known drug carriers and therefore the application of medicaments in liposomal form has been subject of investigation for quite some time.
- An overview concerning (pulmonary) delivery of liposome encapsulated drugs (in asthma therapy) is provided by the review "Pulmonary delivery of liposomes" (H. Schreier, in “Journal of Controlled Release", 24, 1993, p.209-223).
- the physicochemical characterization of liposome aerosols and also their therapeutic applications to the respiratory tract are shown therein.
- Drugs that have been investigated for pulmonary delivery via liposomes include, e.g. anti-cancer agents, peptides, enzymes, anti-asthmatic and anti-allergic compounds and, as mentioned above, also antibiotics.
- the formulation of liposome aerosols or liposome powder aerosols using, for example a dry powder inhaler has also been described by H.
- liposomes as drug carriers
- liposomes and other particulates as carriers of antiseptic or wound-healing promoting agents for applications in the interior of the body, especially in joints.
- An object of the instant invention is to provide a well tolerated, easily applicable antiseptic and/or wound-healing promoting preparation, which provides protracted release and protracted topical effect of the active agent in the body interior, especially in joints, such as the knee, the hip joint, the elbow, the shoulder joint etc.
- the preparation comprises at least one antiseptic and/or wound healing promoting agent in the form of a particulate carrier preparation, as defined in independent claim 1.
- the invention further comprises a method of treating interior parts of the body, in humans and animals, as defined in independent claim 19.
- the invention is premised on the surprising fact that particulate carriers, especially liposomes, are highly suited as carriers for antiseptic agents, especially for povidone iodine, and for agents promoting the healing of wounds, for application to interior body parts, especially joints.
- the preparations according to this invention permit protracted release of the agent or agents, and provide an extended and topical activity at the desired locus of action by interaction with cell surfaces.
- the body interior is considered to broadly include those parts of the body which are enclosed by the skin, excluding the external skin areas and the cavities which are freely accessible from the outside, basically those leading from the mouth through the gastro-intestinal tract to the organs of excretion, and those leading from the nose into the lung.
- anti-inflammatory agents are understood to include antiseptic agents, antibiotic agents, corticosteroids, and wound-healing agents, as defined below.
- antiseptic agents are understood to include those disinfecting agents which are pharmaceutically acceptable and suitable for the treatment of the interior of the human or animal body to the extent that they can be formulated in accordance with the invention.
- antiseptic agents include inter alia oxygen- and halogen-releasing compounds; metal compounds, e.g. silver and mercury compounds; organic disinfectants including mter alia formaldehyde-releasing compounds, alcohols, phenols including alkyl- and arylphenols as well as halogenated phenols, quinolines and acridines, hexahydropyrimidines, quaternary ammonium compounds and iminium salts, and guanidines.
- metal compounds e.g. silver and mercury compounds
- organic disinfectants including mter alia formaldehyde-releasing compounds, alcohols, phenols including alkyl- and arylphenols as well as halogenated phenols, quinolines and acridines, hexahydropyrimidines, quaternary ammonium compounds and iminium salts, and guanidines.
- Wound-healing agents comprise agents promoting granulation and epithelization such as dexpanthenol, allantoines, azulenes, tannines, and vitamine B-type compounds.
- the invention is, another aspect, based on a further surprising and unexpected fact. It is well known in the art that the formation of new body tissues may cause problems. Thus, it is known that body tissue repair may be accompanied by the formation of scar tissue, which can be functionally and/or cosmetically harmful, or at least undesirable. Hyperkeratosis and the uncontrolled proliferation of tissue may cause serious harm, leading to dysfunctions, and may of course also be cosmetically undesirable. After infections and inflammations, re-growing or healing tissue may cause neoplasms and intergrowth. It is thus well known in the art that in the curing of diseases, proper remodelling of tissue is not only desirable, but in fact necessary.
- One object achieved by the invention is therefore concerned with improved tissue repair in the body.
- the invention achieves this by the application of anti- inflammatory agents, in the form of a particulate carrier preparation as defined in the independent claims.
- the antiseptic or wound-healing preparation will generally be administered to the interior body part to be treated by invasive methods, especially by injection of the particulate carrier preparation, or by application of the respective preparation after a surgical step providing access to the locus of treatment.
- a liposome preparation can be made by loading liposomes with PVP iodine in a conventional procedure.
- the nature or constitution of the liposomes are not critical.
- the liposome preparation as, for example, described in EP 0 639 373 can be administered by injection. The disclosure of EP 0 639 373 is incorporated by reference.
- the preparations according to this invention apparently do not only contain the active agent, like povidone iodine, encapsulated in the particulate carrier, especially in liposomes.
- the preparations according to the invention often show a marked initial effect which is observed in addition to the slower, protracted release of the active agent from the carrier. This effect is especially observed where the carrier comprises liposomes.
- the carrier comprises liposomes.
- active agent in addition to active agent encapsulated inside the liposomes, some active agent is present outside of the liposomes, and probably losely bound to the outer surfaces of the liposomes. This could be due to association of active agent molecules with the liposomal membrane, or it could be due to active agent molecules forming a layer on the liposomal surface, which layer partly or even fully coats the liposome externally.
- the type and amount of this initial agent effect can e.g. be influenced by choice of the concentration parameters.
- Anti-inflammatory preparations according to this invention thus make it possible to achieve effects which cannot be provided by customary preparations.
- Preferred antiseptic agents comprise the well-known pharmaceutical substances providing fast effect, a broad range of activity, low systemic toxicity and good tissue compatibility. They can e.g. be selected from the group comprising metal compounds, phenolic compounds, detergents, iodine and iodine complexes. A specifically preferred antiseptic agent is povidone iodine.
- Preferred agents promoting the healing of wounds comprise substances which have been described in the literature for such application.
- Preferred such agents include substances known to promote epithelisation. These include vitamins, specifically from the vitamin B group, allantoin, some azulenes etc.
- the invention's preparations containing antiseptic and/or wound-healing promoting agents can comprise further agents such as anaesthetic agents.
- Inventive preparations can also contain customary further agents, including adjuvants and additives, antioxidants, conserving agents or consistency-forming agents such as viscosity adjusting additives, emulgators etc.
- liposome forming systems comprising lecithine are preferred.
- Such systems can comprise hydrogenated soy bean lecithine besides cholesterol and disodium succinate- hexahydrate; it is presently specificially preferred to use hydrogenated soy bean lecithine as the sole membrane forming agent.
- liposome structures can generally be used in the context of the invention.
- these methods comprise mechanical agitation of a suitable mixture containg the membrane forming substance and water or an aqueous solution. Filtration through suitable membranes is preferred in forming a substantially uniform liposome size.
- the size of the liposomes can vary over a broad range, generally from about 1 to about 20,000 nm. Liposomes with diameters between 50 and 4,000 nm are preferred and liposomes of up to approximately 1,000 nm diameter are presently most preferred. For solutions, smaller average diameters may be more suitable.
- particulate carriers are generally prepared as known in the art.
- microspheres which are used to deliver a very wide range of therapeutic or cosmetic agents, are made as described for example in WO 95/15118.
- Nanoparticles may in some cases be used, provided that they can be loaded with a sufficient amount of active agent and can be administered according to this invention. They can be prepared according to the methods known in the art, as e.g. described by Heyder (GSF Munchen) in "Drugs delivered to the lung, Abstracts IV, Hilton Head Island Conference, May 1998.
- PLD pulse laser deposition
- a further suitable delivery system employs "Large Porous Particles” as disclosed by David A. Edwards et al. in “Large Porous Particles for Pulmonary Drug Delivery” (Science, 20. June 1997, Vol. 276, p. 1868-1871).
- concentrations in the preparation, particle sizes, active agent loadings etc. will be selected for such alternative carriers to correspond basically to the parameters discussed herein with respect to liposome preparations. Selecting and providing such parameter based mter alia on straightforward experimentation, is well within the skill of an ordinary worker experienced in this art.
- a presently highly preferred use of the inventive liposome preparations is in the local treatment of infections of joints, such as the knee, hip, elbow and shoulder joints, especially when the liposome preparations contain povidone iodine.
- the inventive antiseptic preparations especially those containing PVP iodine, have the great advantage of not causing resistances and lead to much less allergic reactions, while permitting a very cost-efficient therapy with a broad spectrum of effect.
- a povidone iodine liposome preparation according to this invention is e.g. effective against viruses. This effect is not provided by antibiotic agents.
- a liposome preparation of a microbicidal agent such as povidone iodine provides protracted release of the agent from liposomes. This leads to extended effect of the antimicrobial substance, and thus less frequent application, as compared with the customary antiseptic solution preparations.
- the present invention is also useful in the treatment of infectious diseases or for alleviation of diseases such as HIV infections which are accompanied by opportunistic infections.
- patients having a suppressed immune system for example, after organ transplants, can be treated according to the invention.
- acute and chronical bronchitis, pneumonia, bronchiectasia, cystic fibrosis, diphtheria, tuberculosis can be treated with the povidone iodine preparation according to the invention.
- Another highly preferred use is in tissue repair, especially in functional and cosmetic tissue remodelling.
- Preparations according to this invention can take a variety of forms, including solutions, dispersions, sprays and gels. Solid forms may sometimes be useful or even advantageous, but are generally less preferred than liquid forms.
- amout of active agents in an inventive preparation will be determined by the desired effect, on the one hand, and the carrying capacity of the carrier preparation for the agent, on the other hand.
- a solution or dispersion of active agent in an inventive carrier preparation can range in concentration between the lower limit of effectiveness of the agent and the solubility or dispersability limit of the agent in the respective solvent, dispersant, spray or gel.
- a solution or dispersion in an inventive carrier preparation can contain between 0.1 and 10 g of agent in 100 g of preparation.
- Such a preparation will then typically contain between 1 and 5 g of liposome membrane forming substance, esepcially lecithine, per 100 g of preparation.
- an injectable preparation which comprises up to 10 % povidone iodine (at 10 % iodine content) in a physiological saline liposome dispersion.
- povidone iodine is exemplified as an antiseptic agent and liposomes are chosen as the carrier.
- One preferred method for producing the invention's liposomes can generally be described as follows:
- the lipid membrane-forming components e.g. lecithine
- a suitable solvent such as chloroform or a 2:1 mixture of methanol and chloroform and are filtered under sterile conditions.
- a lipid film is produced on a sterile high surface substrate, such as glass beads, by controlled evaporation of the solvent.
- An aqueous system is prepared from electrolyte components and the (one or more) active agents to be incorporated in the liposome preparation.
- Such an aqueous system can e.g. comprise 10 mmol/1 sodium hydrogen phosphate and 0.9 % sodium chloride, at ph 7.4; the aqueous system will further comprise at least the desired amount of the active agent, which in the embodiment examples is povidone iodide.
- the aqueous system will comprise an excess amount of agent or agents.
- the liposomes are generally formed by agitating said aqueous system in the presence of said film formed by the lipid components. At this stage, further additives can be added to improve liposome formation; e.g. sodium cholate can be added. Liposome formation can also be influenced by mechanical action such as pressure filtration through e.g. polycarbonate membranes, or centrifuging. Generally, the raw liposome dispersion will be washed, e.g. with electrolyte solution as used in preparing the above-described solution of the active agent.
- liposomes with the required size distribution When liposomes with the required size distribution have been obtained and washed, they can be redispersed in an electrolyte solution as already described, often also comprising sugars such as saccharose or a suitable sugar substitute.
- the dispersion can be freeze-dried, and it can be lyophilysed. It can, prior to use, be reconstituted by addition of water and suitable mechanical agitation at the transition temperature of the lipid component, which for hydrogenated soy bean lecithine is e.g. 55°C.
- the PVP iodine solution was then added to the lipid film in the flask and the mixture was shaken until the film dissolved.
- the resulting liposome formulation was seperated from the hydrated lipids in the flask.
- the product was centrifuged and the supernatant liquid was discarded.
- the saccharose solution was added ad 12 ml and the product was again centrifuged. Afterwards the supernatant liquid was again discarded. At this stage, a further washing step, using the saccharose solution or the sodium chloride buffer solution could be used.
- sodium chloride buffer solution was added ad 12 ml, and the liposomes were homogenously distributed therein.
- the product was then distributed into vials each containing 2 ml liposome dispersion, and the vials were then subjected to a freeze-drying step.
- each vial comprised about 40 mg solids.
- Embodiment Example II The method of Embodiment Example I has a minor disadvantage in that the PVP iodine solution used, due to the high percentage of solids, is rather viscous and thus more difficult to handle.
- Emhodiment FxRmple II The method of Embodiment Example II
- the product was centrifuged and the supernatant liquid was discarded. 5
- the above-described method uses a hydrating o step after film formation in the presence of organic solvents and aims at inclusion rates of 5 bis 15 %. These methods generally produce rather large and often multi- lamellar liposomes.
- the above-described methods can be modified by a high pressure filtering step through a suitable membrane such as a polycarbonate membrane after the raw liposomes have been formed or after any of the subsequent washing steps or directly by using high pressure homogenisation. This produces much smaller, unilamellar liposomes at increased amounts of encapsulated agent.
- An injectable dispersion was prepared from 10 g hydrogenated soy bean lecithine/PVP iodine liposomes as described in Embodiment Example II; these were mixed with physiological saline ad 100 g.
- the dispersion of Embodiment Example III can have an additional content of an agent known to promote the healing of wounds, such as allantoin.
- an agent will be added in a pharmaceutically useful concentration, in the case of allantoin in the range of 0.1 to 0.5 g, per 100 g of dispersion.
- the wound-healing agent can be incorporated in the saline, in which case it will largely be outside the liposomes. It can, however, be partly or mostly incorporated in the liposomes, in which case it will be added at a corresponding suitable stage of the liposome preparation method.
- Embodiment Examples Presently, it is however preferred to use a wound healing promoting agent (if at all) in addition to an antiseptic agent.
- the liposome preparation used was that of Embodiment Example I. At different contact times between 1 und 120 minutes, the minimum concentration of the preparation in water was determined which was capable of killing the staphilococci.
- the results show that at short contact times (between 1 and 4 minutes) the bactericidal concentration is as low as 0.06 % and that at long contact times (120 minutes) the bactericidal concentration can be as low as 0.007 %.
- liposomal PVP-iodine The virucidal and chlamydicidal activity of liposomal PVP-iodine has been studied, in cell cultures, by Wutzler et al., 9th European Congress for Clinic Microbiology and Infection Diseases, Berlin, March 1999.
- liposomal PVP-iodine is highly effective against herpes simplex virus type 1 and adeno virus tpye 8, while the long-term cytotoxicit experiments indicated that the liposomal form is better tolerated than aqueous PVP-iodine by the majority of cell lines tested.
- PVP-iodine in liposomal form is not genotoxic.
- a 3% PVP-iodine hydrogel liposomal preparation was compared with a 3% PVP- iodine ointment, where the active agent was not in liposomal form.
- the agent was applied to standardized in vitro cultures of rat skin and peritoneal explants, as a screening for tissue compatibility of skin and wound antiinfectives.
- the growth rate of the cultured explants was studied after 30 minutes exposure and incubation with a test substance.
- the peritoneum growth rate reached 85%, and the skin growth rate reached 90%; with the liposomal hydrogel formulation, the peritoneum growth rate was 96%, and the skin growth rate was 108%; these values are to be compared with 100% values in a control test using Ringer's solution as the agent.
- Sesamoid bones were dissected within 2-4 h after slaughter from bovine metacarpo- phalangeal joints of adult animals under aseptic conditions.
- the cartilage from sesamoid bones of a particular animal is uniform with respect to glycosaminoglycan synthesis, glycosaminoglycan content, and proteoglycan composition.
- Each experimental group consisted of eight sesamoid bones from the same animal.
- the sesamoid bones were washed in 10 ml cold sterile Ringer's solution for 10 min, incubated respectively in 10 ml of sterile Ringer's solution (control), PVP-iodine, or PVP-iodine dilutions with Ringer's solution (1 :10, 1 :100, or 1 :1000) at 37°C for 10 min in a humidified atmosphere of 5 % CO 2 in air, and subsequently washed again for 5 x 5 min in 10 ml Ringer's solution in each case.
- cartilage plugs of 2.8 mm in diameter were carefully removed and extracted thereafter in a stepwise manner.
- the culture media of sesamoid bones and extracts of cartilage plugs were used for the quantitative and qualitative characterization of proteoglycans and COMP (cartilage oligomeric matrix protein), because an increased release of fragments of these cartilage matrix constituents equals to a catabolic pathway.
Abstract
Description
Claims
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00936804A EP1180018B1 (en) | 1999-05-27 | 2000-05-25 | Use of antiseptics in the manufacture of a pharmaceutical preparation for the prevention and treatment of infections and/ or functional tissue remodelling in the interior of the human body |
AT00936804T ATE289805T1 (en) | 1999-05-27 | 2000-05-25 | USE OF ANTISEPTICS FOR THE PRODUCTION OF MEDICINAL PRODUCTS FOR THE PROPHYLAXIS AND TREATMENT OF INFECTIONS AND/OR FUNCTIONAL TISSUE FORMATION INSIDE THE BODY |
IL14613300A IL146133A0 (en) | 1999-05-27 | 2000-05-25 | Preparations for the application of anti-inflammatory agents |
US09/979,852 US7468194B1 (en) | 1999-05-27 | 2000-05-25 | Preparations for the application of anti-inflammatory agents |
DE60018409T DE60018409T2 (en) | 1999-05-27 | 2000-05-25 | USE OF ANTISEPTICA FOR THE PREPARATION OF MEDICAMENTS FOR THE PROPHYLAXIS AND THE TREATMENT OF INFECTIONS AND / OR FUNCTIONAL TISSUE FORMATIONS IN THE BODY'S INSECTS |
BR0010983-5A BR0010983A (en) | 1999-05-27 | 2000-05-25 | Preparations for the application of anti-inflammatory agents |
AU52166/00A AU772314B2 (en) | 1999-05-27 | 2000-05-25 | Preparations for the application of anti-inflammatory agents |
CA002368192A CA2368192A1 (en) | 1999-05-27 | 2000-05-25 | Preparations for the application of antiseptic agents to the interior of the human or animal body |
MXPA01012170A MXPA01012170A (en) | 1999-05-27 | 2000-05-25 | Preparations for the application of anti-inflammatory agents. |
JP2000620935A JP5616565B2 (en) | 1999-05-27 | 2000-05-25 | Formulations for applying anti-inflammatory agents |
HU0201038A HU229598B1 (en) | 1999-05-27 | 2000-05-25 | Preparations for the application of anti-inflammatory agents |
IL146133A IL146133A (en) | 1999-05-27 | 2001-10-23 | Preparations for the application of anti-inflammatory agents |
HK02107827.2A HK1046242B (en) | 1999-05-27 | 2002-10-29 | Preparations for the application of anti-inflammatory agents |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19924313 | 1999-05-27 | ||
DE19924313.1 | 1999-05-27 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2000072823A1 true WO2000072823A1 (en) | 2000-12-07 |
WO2000072823A8 WO2000072823A8 (en) | 2001-06-07 |
Family
ID=7909362
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2000/004783 WO2000072823A1 (en) | 1999-05-27 | 2000-05-25 | Preparations for the application of anti-inflammatory agents |
Country Status (20)
Country | Link |
---|---|
US (1) | US7468194B1 (en) |
EP (2) | EP1502586B1 (en) |
JP (1) | JP5616565B2 (en) |
KR (1) | KR100687781B1 (en) |
CN (1) | CN1197552C (en) |
AT (2) | ATE340561T1 (en) |
AU (1) | AU772314B2 (en) |
BR (1) | BR0010983A (en) |
CA (1) | CA2368192A1 (en) |
CY (1) | CY1105849T1 (en) |
DE (3) | DE60031016T2 (en) |
DK (1) | DK1502586T3 (en) |
ES (2) | ES2235891T3 (en) |
HK (2) | HK1046242B (en) |
HU (1) | HU229598B1 (en) |
IL (2) | IL146133A0 (en) |
MX (1) | MXPA01012170A (en) |
PT (1) | PT1502586E (en) |
RU (1) | RU2264827C2 (en) |
WO (1) | WO2000072823A1 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003342171A (en) * | 2002-05-23 | 2003-12-03 | Usv Ltd | Composition for administering dithranol |
US7297344B1 (en) | 1999-05-27 | 2007-11-20 | Euro-Celtique, S.A. | Preparations for the promotion of wound healing in the upper respiratory tract and/or ear |
US7300667B1 (en) | 1999-05-27 | 2007-11-27 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract |
WO2009010707A1 (en) * | 2007-07-13 | 2009-01-22 | Prototype Bioforum Limited | Injectable pharmaceutical compositions containing panthenol |
WO2013078998A1 (en) * | 2011-11-29 | 2013-06-06 | Jiangsu Deda Pharmaceuticals Co., Ltd | Novel slow-releasing ophthalmic compositions comprising povidone iodine |
CN104147610A (en) * | 2014-06-26 | 2014-11-19 | 中国人民解放军第三○九医院 | Antibiotic constituent loaded polymer micro-nanoparticle and preparation method thereof |
US8906966B2 (en) | 2006-07-13 | 2014-12-09 | Paul Sherwood | Medicaments containing panthenol |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE235895T1 (en) * | 1998-05-27 | 2003-04-15 | Euro Celtique Sa | DRUG DELIVERY SYSTEM CONTAINING A HARD-PACKED, SOLID DRUG BASE |
ATE371436T1 (en) | 2003-05-19 | 2007-09-15 | Euro Celtique Sa | DRY LIPOSOMAL PVP-IODINE PREPARATIONS |
DE102005063375A1 (en) * | 2005-09-15 | 2007-04-19 | Schülke & Mayr GmbH | Antimicrobial preparations containing octenidine dihydrochloride encapsulated in liposomes |
CN101987109B (en) * | 2009-08-05 | 2012-07-04 | 天津金耀集团有限公司 | Ophthalmic composition containing povidone iodine and cyclodextrin included glucocorticoid |
CN103143053A (en) * | 2013-03-24 | 2013-06-12 | 山东康力医疗器械科技有限公司 | Novel povidone-iodine antibacterial hydrocolloid dressing and preparation method thereof |
CN106307543B (en) * | 2016-08-22 | 2020-02-07 | 青岛农业大学 | Thymol nano liposome and preparation method thereof |
CN109180600A (en) * | 2018-09-21 | 2019-01-11 | 五邑大学 | A kind of thymol analog and its application |
CN111329824A (en) * | 2020-04-02 | 2020-06-26 | 东元科技有限公司 | Hand sanitizer with strong sterilization capability |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0639373A1 (en) * | 1993-08-20 | 1995-02-22 | Euroceltique S.A. | Preparations for the external application of antiseptic agents and/or agents promoting the healing of wounds |
WO1996014083A1 (en) * | 1994-11-04 | 1996-05-17 | Polymun Scientific Immunbiologische Forschung Gmbh | Application of superoxide dismutase in liposomes |
WO1999060998A1 (en) * | 1998-05-27 | 1999-12-02 | Euroceltique S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the upper respiratory tract and/or the ear |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE615889A (en) | 1952-04-15 | 1900-01-01 | ||
US4113857A (en) | 1977-05-16 | 1978-09-12 | The Purdue Frederick Company | Process for the preparation of iodophor compounds and methods for stabilizing iodophor pharmaceutical compositions containing the same |
US4675009A (en) | 1977-11-07 | 1987-06-23 | Lec Tec Corporation | Drug dispensing device for transdermal delivery of medicaments |
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
FR2536278A1 (en) | 1982-11-18 | 1984-05-25 | Dupont Michele | NOVEL THERAPEUTIC COMPOSITION USEFUL IN PARTICULAR FOR WOUND HEALING |
US4523589A (en) * | 1983-06-29 | 1985-06-18 | Krauser Robert S | Method and apparatus for treating ailments |
FR2591105B1 (en) | 1985-12-11 | 1989-03-24 | Moet Hennessy Rech | PHARMACEUTICAL COMPOSITION, IN PARTICULAR DERMATOLOGICAL, OR COSMETIC, BASED ON HYDRATED LIPID LAMELLAR PHASES OR LIPOSOMES CONTAINING A RETINOIDE OR A STRUCTURAL ANALOG OF SUCH A RETINOID AS A CAROTENOID. |
SE8603812D0 (en) | 1986-09-12 | 1986-09-12 | Draco Ab | ADMINISTRATION OF LIPOSOMES TO MAMMALS |
US5049388A (en) | 1986-11-06 | 1991-09-17 | Research Development Foundation | Small particle aerosol liposome and liposome-drug combinations for medical use |
IE63869B1 (en) * | 1986-11-06 | 1995-06-14 | Res Dev Foundation | Aerosols containing liposomes and method for their preparation |
JPH0761940B2 (en) | 1986-11-17 | 1995-07-05 | 株式会社資生堂 | Liposomal formulation for outer skin |
CH672733A5 (en) | 1987-05-22 | 1989-12-29 | Bracco Ind Chimica Spa | |
US4938965A (en) | 1987-07-22 | 1990-07-03 | Her Majesty The Queen In Right Of Canada, As Represented By The Minister Of National Defence Of Her Majesty's Canadian Government | Ocular delivery of prophylactic agents |
US5246708A (en) | 1987-10-28 | 1993-09-21 | Pro-Neuron, Inc. | Methods for promoting wound healing with deoxyribonucleosides |
CA1303503C (en) | 1987-11-10 | 1992-06-16 | Marc Plamondon | Ophthalmic solution comprising iodine-polyvinylpyrrolidone complex |
DE3826946C1 (en) | 1988-08-09 | 1990-03-15 | A. Nattermann & Cie Gmbh, 5000 Koeln, De | |
US4906476A (en) | 1988-12-14 | 1990-03-06 | Liposome Technology, Inc. | Novel liposome composition for sustained release of steroidal drugs in lungs |
JPH02204413A (en) | 1989-02-02 | 1990-08-14 | Nonogawa Shoji:Kk | Antimycotic agent for external use |
AU633078B2 (en) | 1989-04-04 | 1993-01-21 | Alcon Laboratories, Inc. | The use of liposomes for the delivery of therapeutic agents to wounds, cuts and abrasions |
US5232692A (en) | 1989-04-28 | 1993-08-03 | Research And Education Institute, Inc. | Povidone-iodine neonatal ophthalmic antimicrobial prophylactic agent |
EP0407028B2 (en) | 1989-05-31 | 1999-07-07 | FISONS plc | Medicament inhalation device and formulation |
US5128139A (en) | 1991-02-15 | 1992-07-07 | Nu Skin International, Inc. | Composition containing liposome-entrapped grapefruit seed extract and method for making |
DE4111982C2 (en) | 1991-04-12 | 1998-12-24 | Merz & Co Gmbh & Co | Stable small particulate liposome preparations, their preparation and use |
WO1992018106A1 (en) | 1991-04-16 | 1992-10-29 | Nippon Shinyaku Co., Ltd. | Method of manufacturing solid dispersion |
CA2109528A1 (en) | 1991-05-01 | 1992-11-02 | Gregory A. Prince | A method for treating infectious respiratory diseases |
WO1993024165A1 (en) | 1992-05-29 | 1993-12-09 | Ggu Gesellschaft Für Gesundheits- Und Umweltforschung Mbh & Co. Vertriebs Kg | Device for generating inhalable active substance particles |
AU4066693A (en) | 1992-12-23 | 1994-07-19 | Bernhard Hugemann | Compacted drug body for use in the mechanical generation of inhalable active-substance particles |
US5552158A (en) | 1993-02-23 | 1996-09-03 | Norac Technologies Inc. | Skin care composition |
DE4306475A1 (en) | 1993-03-02 | 1994-09-08 | Ensenat Pedro Gonzalez | Liposomes containing chlorhexidine diacetate or chlorhexidine digluconate |
US5270307A (en) | 1993-03-26 | 1993-12-14 | The Dow Chemical Company | Pyrrolo(1,2-b)-(1,2)-benzothiazin-10-one and its use as an antimicrobial |
US5863556A (en) * | 1993-08-20 | 1999-01-26 | Euro-Celtique, S.A. | Preparations for the external application of antiseptic agents and/or agents promoting the healing of wounds |
US20010055610A1 (en) | 1997-06-06 | 2001-12-27 | Shunji Nagata | Medicament administration system |
-
2000
- 2000-05-25 AT AT04025138T patent/ATE340561T1/en active
- 2000-05-25 DE DE60031016T patent/DE60031016T2/en not_active Expired - Lifetime
- 2000-05-25 ES ES00936804T patent/ES2235891T3/en not_active Expired - Lifetime
- 2000-05-25 IL IL14613300A patent/IL146133A0/en active IP Right Grant
- 2000-05-25 US US09/979,852 patent/US7468194B1/en not_active Expired - Fee Related
- 2000-05-25 HU HU0201038A patent/HU229598B1/en not_active IP Right Cessation
- 2000-05-25 CN CNB008081484A patent/CN1197552C/en not_active Expired - Fee Related
- 2000-05-25 EP EP04025138A patent/EP1502586B1/en not_active Expired - Lifetime
- 2000-05-25 MX MXPA01012170A patent/MXPA01012170A/en active IP Right Grant
- 2000-05-25 DE DE60018409T patent/DE60018409T2/en not_active Expired - Lifetime
- 2000-05-25 KR KR1020017015018A patent/KR100687781B1/en not_active IP Right Cessation
- 2000-05-25 CA CA002368192A patent/CA2368192A1/en not_active Abandoned
- 2000-05-25 JP JP2000620935A patent/JP5616565B2/en not_active Expired - Fee Related
- 2000-05-25 EP EP00936804A patent/EP1180018B1/en not_active Expired - Lifetime
- 2000-05-25 PT PT04025138T patent/PT1502586E/en unknown
- 2000-05-25 RU RU2001135842/15A patent/RU2264827C2/en not_active IP Right Cessation
- 2000-05-25 BR BR0010983-5A patent/BR0010983A/en not_active Application Discontinuation
- 2000-05-25 ES ES04025138T patent/ES2274372T3/en not_active Expired - Lifetime
- 2000-05-25 AU AU52166/00A patent/AU772314B2/en not_active Ceased
- 2000-05-25 DE DE20022718U patent/DE20022718U1/en not_active Expired - Lifetime
- 2000-05-25 DK DK04025138T patent/DK1502586T3/en active
- 2000-05-25 WO PCT/EP2000/004783 patent/WO2000072823A1/en active IP Right Grant
- 2000-05-25 AT AT00936804T patent/ATE289805T1/en active
-
2001
- 2001-10-23 IL IL146133A patent/IL146133A/en not_active IP Right Cessation
-
2002
- 2002-10-29 HK HK02107827.2A patent/HK1046242B/en not_active IP Right Cessation
-
2005
- 2005-07-13 HK HK05105975A patent/HK1073252A1/en not_active IP Right Cessation
-
2006
- 2006-12-13 CY CY20061101794T patent/CY1105849T1/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0639373A1 (en) * | 1993-08-20 | 1995-02-22 | Euroceltique S.A. | Preparations for the external application of antiseptic agents and/or agents promoting the healing of wounds |
WO1996014083A1 (en) * | 1994-11-04 | 1996-05-17 | Polymun Scientific Immunbiologische Forschung Gmbh | Application of superoxide dismutase in liposomes |
WO1999060998A1 (en) * | 1998-05-27 | 1999-12-02 | Euroceltique S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the upper respiratory tract and/or the ear |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7297344B1 (en) | 1999-05-27 | 2007-11-20 | Euro-Celtique, S.A. | Preparations for the promotion of wound healing in the upper respiratory tract and/or ear |
US7300667B1 (en) | 1999-05-27 | 2007-11-27 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract |
JP2003342171A (en) * | 2002-05-23 | 2003-12-03 | Usv Ltd | Composition for administering dithranol |
US8906966B2 (en) | 2006-07-13 | 2014-12-09 | Paul Sherwood | Medicaments containing panthenol |
WO2009010707A1 (en) * | 2007-07-13 | 2009-01-22 | Prototype Bioforum Limited | Injectable pharmaceutical compositions containing panthenol |
WO2013078998A1 (en) * | 2011-11-29 | 2013-06-06 | Jiangsu Deda Pharmaceuticals Co., Ltd | Novel slow-releasing ophthalmic compositions comprising povidone iodine |
US9308173B2 (en) | 2011-11-29 | 2016-04-12 | Iview Therapeutics, Inc. | Slow-releasing ophthalmic compositions comprising povidone iodine |
CN104147610A (en) * | 2014-06-26 | 2014-11-19 | 中国人民解放军第三○九医院 | Antibiotic constituent loaded polymer micro-nanoparticle and preparation method thereof |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU752018C (en) | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract | |
EP1180018B1 (en) | Use of antiseptics in the manufacture of a pharmaceutical preparation for the prevention and treatment of infections and/ or functional tissue remodelling in the interior of the human body | |
US7297344B1 (en) | Preparations for the promotion of wound healing in the upper respiratory tract and/or ear | |
US7364749B1 (en) | Preparations for the application of anti-infective and/or anti-inflammatory agents | |
US7300667B1 (en) | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract | |
MXPA00011649A (en) | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 00808148.4 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
AK | Designated states |
Kind code of ref document: C1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: C1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
CFP | Corrected version of a pamphlet front page | ||
CR1 | Correction of entry in section i | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2000936804 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2368192 Country of ref document: CA Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: IN/PCT/2001/01002/DE Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 52166/00 Country of ref document: AU |
|
ENP | Entry into the national phase |
Ref document number: 2000 620935 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020017015018 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2001/012170 Country of ref document: MX Ref document number: 09979852 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 1020017015018 Country of ref document: KR |
|
WWP | Wipo information: published in national office |
Ref document number: 2000936804 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWG | Wipo information: grant in national office |
Ref document number: 52166/00 Country of ref document: AU |
|
WWG | Wipo information: grant in national office |
Ref document number: 2000936804 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 1020017015018 Country of ref document: KR |