CA2382359C - Pharmaceutical preparation containing nanosol - Google Patents
Pharmaceutical preparation containing nanosol Download PDFInfo
- Publication number
- CA2382359C CA2382359C CA002382359A CA2382359A CA2382359C CA 2382359 C CA2382359 C CA 2382359C CA 002382359 A CA002382359 A CA 002382359A CA 2382359 A CA2382359 A CA 2382359A CA 2382359 C CA2382359 C CA 2382359C
- Authority
- CA
- Canada
- Prior art keywords
- active substance
- pharmaceutical preparation
- preparation according
- chitosan derivative
- production
- 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.)
- Expired - Fee Related
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/0004—Preparation of sols
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/0004—Preparation of sols
- B01J13/0039—Post treatment
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to solid pharmaceutical preparations with an at least partially charged active substance in the form of a nanosol in which the active substance is bound to an oppositely charged chitosane derivative. The invention further relates to a method of production and to the use of said preparations in the production of medicaments.
Description
i . . =
FfiARMACRVTICAL FRSPARATION CONTAINXNG ATA1+tOSOL
Pharmaceutical preparations wherain an active substance is precent bound to a carrier are known ir- the gtate of the art in great tbundance. In the widest sense, the bond to the carrier can be understood to be purely mechanical; in a narrovr-senso, however, one makes use of the capacity of carrier subgta=sceg to enter into speoial chemical or pryaicochemicai interactions with tho active substance or substances. One catogory of such interactions are ionic attractive forces, which of course can only be made use of Lf active agent and carrier are at least partially proaent in a charged state. 2n pharmaceutical preparations, ionic bonds between active oubstances and carriers are used, inter alia, to preserve sparingly soluble activo substances which have a low tendency of dissociation in water in their charged and molecular-disperse state, theraby obtaining a high dissolution rate. Apart from this, active ag nts are bonded to oppositely charged oarrier polymers to enable a high active substance load of the preparationf this formulation technique ie frequently used, for instance, in liposomo preparations. A further variant which has been described are preparations wherein by way of the ionic bozxd to a charged polymer it is intended to achieve a controlled reloase of active substance. An example for this is the cough mixture marketed in Germany under the mark Codiprout which contains as active substance carrier complex an active subgtance base, Codeine Poly(styrene, di.vinyl benzene)sulfonate, bonded to an acidic ion exchanger.
A special form of active agents bound to opposxtely cksax$e$
cazxiers are the sa-called naAomols with gelatine or r collagen hydrolysates as carriers, which are described by the firm of Alfatec-Pharma GmbH in various patents and published applications, e.g., in the documents DE 41 40 195, DE 41 40 178 and DE 41 40 179. Here, one makes use of the fact that it is easily possible to achieve the desired, isoionic state with charge equalization between carrier and active substance if gelatine or gelatine derivatives are used, thanks to the zwitterionic nature of the same, by means of a corresponding pH adjustment in the preparation.
It is described that these nanosols can be used to advan-tage for the production of medicinal preparations both with rapid and with controlled active substance release.
However, these preparations have the disadvantage that the population has been uncertain for several years as to the possible risks of BSE infection and has increasingly been avoiding products containing gelatine, for example.
Therefore, there is a need for preparations without gelatine or collagen derivatives which have the same advantages as, for example, the gelatine-based nanosols described.
It is thus the object of the present invention to provide a pharmaceutical preparation without gelatine or the like, for charged active substances, in which the active substance is present bonded to an oppositely charged carrier.
The object is achieved by a pharmaceutical preparation according to Claim 1.
it was surprisingly found that using chitosans as carriers it is possible to produce so-called nanosols wherein the active substance is present stabilized in a state almost isoionic with the carrier, and that these nanosols are highly suitable for the production of medicinal products.
~
FfiARMACRVTICAL FRSPARATION CONTAINXNG ATA1+tOSOL
Pharmaceutical preparations wherain an active substance is precent bound to a carrier are known ir- the gtate of the art in great tbundance. In the widest sense, the bond to the carrier can be understood to be purely mechanical; in a narrovr-senso, however, one makes use of the capacity of carrier subgta=sceg to enter into speoial chemical or pryaicochemicai interactions with tho active substance or substances. One catogory of such interactions are ionic attractive forces, which of course can only be made use of Lf active agent and carrier are at least partially proaent in a charged state. 2n pharmaceutical preparations, ionic bonds between active oubstances and carriers are used, inter alia, to preserve sparingly soluble activo substances which have a low tendency of dissociation in water in their charged and molecular-disperse state, theraby obtaining a high dissolution rate. Apart from this, active ag nts are bonded to oppositely charged oarrier polymers to enable a high active substance load of the preparationf this formulation technique ie frequently used, for instance, in liposomo preparations. A further variant which has been described are preparations wherein by way of the ionic bozxd to a charged polymer it is intended to achieve a controlled reloase of active substance. An example for this is the cough mixture marketed in Germany under the mark Codiprout which contains as active substance carrier complex an active subgtance base, Codeine Poly(styrene, di.vinyl benzene)sulfonate, bonded to an acidic ion exchanger.
A special form of active agents bound to opposxtely cksax$e$
cazxiers are the sa-called naAomols with gelatine or r collagen hydrolysates as carriers, which are described by the firm of Alfatec-Pharma GmbH in various patents and published applications, e.g., in the documents DE 41 40 195, DE 41 40 178 and DE 41 40 179. Here, one makes use of the fact that it is easily possible to achieve the desired, isoionic state with charge equalization between carrier and active substance if gelatine or gelatine derivatives are used, thanks to the zwitterionic nature of the same, by means of a corresponding pH adjustment in the preparation.
It is described that these nanosols can be used to advan-tage for the production of medicinal preparations both with rapid and with controlled active substance release.
However, these preparations have the disadvantage that the population has been uncertain for several years as to the possible risks of BSE infection and has increasingly been avoiding products containing gelatine, for example.
Therefore, there is a need for preparations without gelatine or collagen derivatives which have the same advantages as, for example, the gelatine-based nanosols described.
It is thus the object of the present invention to provide a pharmaceutical preparation without gelatine or the like, for charged active substances, in which the active substance is present bonded to an oppositely charged carrier.
The object is achieved by a pharmaceutical preparation according to Claim 1.
it was surprisingly found that using chitosans as carriers it is possible to produce so-called nanosols wherein the active substance is present stabilized in a state almost isoionic with the carrier, and that these nanosols are highly suitable for the production of medicinal products.
~
The preparation of the present invention contains according to Claim 1 at least one pharmaceutical active substance, which is at least partially present in a charged state, i.e. the active substance is capable of forming an ionic state and at least part of the active substance molecules are present in that ionic state.
For a definition of a nanosol, reference is made to DE 41 40 195.
Considered as chitosan derivatives in the spirit of the invention are all modified and unmodified deacetylation products of chitin which still possess a polyglucosamine base structure. The charge opposite to that of the active substance, which is demanded according to the present invention, refers to the net-charge of the carrier used.
Thus there may also be charges in the chitosan derivative that are like that of the active substance as long as they are overcompensated by the opposite charges.
in fact, in one of the preferred embodiments there is an active substance with a positive charge that is bonded in the nanosol to a chitosan derivative with negative total charge. Such a chitosan derivative may, for example, be a zwitterionic, partially sulfated chitosan.
in a further, also preferred, embodiment, the active substance is present in a negatively charged state and is bound in the nanosol to a positively charged chitosan derivative, i.e. in the most simple case to an unmodified chitosan. Here, too, an active substance may well be present in a partially undissociated form and may even possess some charges that are like that of the chitosan derivative as long as its net-charge is opposite, i.e. in this case negative.
u Preferably, the active substance is present in the nanosol in a colloidal or nanoparticulate distribution, i.e. with an average particle size of at maximum about 500-1000 nm, as far as it is possible to detect a phase boundary between active substance and carrier phase at all. in particular, poorly soluble active agents can be incorporated in this way in pharmaceutical preparations from which they can be quickly released.
The preparations according to the present invention will as a rule contain further auxiliary agents which are commonly used in the pharmaceutics technology and are known to those skilled in the art. These active auxiliary agents may, for example, be further polymeric or non-polymeric carrier substances, but also stabilisers, surfactants, disinte-gration promoters, antioxidants, dyes, pigments, flavours, sweeteners or other taste-improving agents, binders, lubricants etc. in a preferred embodiment, the preparation contains a further polymeric carrier substance. This can be required, for example, in order to increase the loadability of the nanosol with active substance or in order to modify the release properties of the preparation. Appropriate formulation techniques are likewise known to those skilled in the art.
In accordance with the invention, the herein disclosed pharmaceutical preparations are used for making medicinal products or diagnostic agents. A preferred use of the preparation consists in the production of medicinal agents which are administered as capsules, tablets, powders or granulates, or, like instant preparations, are first dissolved or redispersed in water or another suitable liquid prior to being administered.
~
in a further preferred embodiment, the preparations are used for preparing medicinal products having controlled active substance release. To this end, they must generally be further modified, i.e. mixed with further auxiliary substances or enclosed by these. For instance, capsules or tablets containing a preparation according to the present invention can be coated with a polymeric film which controls the release of the active agent or agents. These and further techniques for producing medicinal products with modified or controlled release of active substance are known to those skilled in the art.
A preparation according to the present invention is basically produced in a multi-step process which can be varied if necessary or complemented by further steps.
initially, a chitosan derivative is selected as carrier, taking into account the relative number and type of the charged groups of the active agent, which on account of the type and relative number of its charged groups is matched with the active substance in such a way that at a certain pH value an isoionic state or charge equalization can be achieved between active substance and carrier. This is generally the case if the net-charges of active substance and chitosan derivative are opposite and the calculated isoionic point is in a pH range that is physiologically acceptable and is not detrimental to the stability of the active substance.
In a further step, a colloidal aqueous solution is prepared from the chitosan derivative and the active substance, which on account of its polymer content and the viscosity resulting therefrom is a sol. it is of no importance here whether the active substance is added following or prior to dissolving the chitosan derivative, or whether a solution of the chitosan derivative and an independently prepared solution of the active substance are united.
~
In a further step, the pH of the aqueous sol is adjusted such that an isoionic state results. In the course of this pH shift a precipitation of the active substance may occur.
It has turned out here that the particles do generally not exceed the colloidal or nanoparticulate size range.
The sol which has been thus prepared and adjusted to an isoionic state can be dried in a further process step. For this purpose, conventional drying methods, but preferably drying methods applying no or only little heat such as freeze drying, may be used.
For a definition of a nanosol, reference is made to DE 41 40 195.
Considered as chitosan derivatives in the spirit of the invention are all modified and unmodified deacetylation products of chitin which still possess a polyglucosamine base structure. The charge opposite to that of the active substance, which is demanded according to the present invention, refers to the net-charge of the carrier used.
Thus there may also be charges in the chitosan derivative that are like that of the active substance as long as they are overcompensated by the opposite charges.
in fact, in one of the preferred embodiments there is an active substance with a positive charge that is bonded in the nanosol to a chitosan derivative with negative total charge. Such a chitosan derivative may, for example, be a zwitterionic, partially sulfated chitosan.
in a further, also preferred, embodiment, the active substance is present in a negatively charged state and is bound in the nanosol to a positively charged chitosan derivative, i.e. in the most simple case to an unmodified chitosan. Here, too, an active substance may well be present in a partially undissociated form and may even possess some charges that are like that of the chitosan derivative as long as its net-charge is opposite, i.e. in this case negative.
u Preferably, the active substance is present in the nanosol in a colloidal or nanoparticulate distribution, i.e. with an average particle size of at maximum about 500-1000 nm, as far as it is possible to detect a phase boundary between active substance and carrier phase at all. in particular, poorly soluble active agents can be incorporated in this way in pharmaceutical preparations from which they can be quickly released.
The preparations according to the present invention will as a rule contain further auxiliary agents which are commonly used in the pharmaceutics technology and are known to those skilled in the art. These active auxiliary agents may, for example, be further polymeric or non-polymeric carrier substances, but also stabilisers, surfactants, disinte-gration promoters, antioxidants, dyes, pigments, flavours, sweeteners or other taste-improving agents, binders, lubricants etc. in a preferred embodiment, the preparation contains a further polymeric carrier substance. This can be required, for example, in order to increase the loadability of the nanosol with active substance or in order to modify the release properties of the preparation. Appropriate formulation techniques are likewise known to those skilled in the art.
In accordance with the invention, the herein disclosed pharmaceutical preparations are used for making medicinal products or diagnostic agents. A preferred use of the preparation consists in the production of medicinal agents which are administered as capsules, tablets, powders or granulates, or, like instant preparations, are first dissolved or redispersed in water or another suitable liquid prior to being administered.
~
in a further preferred embodiment, the preparations are used for preparing medicinal products having controlled active substance release. To this end, they must generally be further modified, i.e. mixed with further auxiliary substances or enclosed by these. For instance, capsules or tablets containing a preparation according to the present invention can be coated with a polymeric film which controls the release of the active agent or agents. These and further techniques for producing medicinal products with modified or controlled release of active substance are known to those skilled in the art.
A preparation according to the present invention is basically produced in a multi-step process which can be varied if necessary or complemented by further steps.
initially, a chitosan derivative is selected as carrier, taking into account the relative number and type of the charged groups of the active agent, which on account of the type and relative number of its charged groups is matched with the active substance in such a way that at a certain pH value an isoionic state or charge equalization can be achieved between active substance and carrier. This is generally the case if the net-charges of active substance and chitosan derivative are opposite and the calculated isoionic point is in a pH range that is physiologically acceptable and is not detrimental to the stability of the active substance.
In a further step, a colloidal aqueous solution is prepared from the chitosan derivative and the active substance, which on account of its polymer content and the viscosity resulting therefrom is a sol. it is of no importance here whether the active substance is added following or prior to dissolving the chitosan derivative, or whether a solution of the chitosan derivative and an independently prepared solution of the active substance are united.
~
In a further step, the pH of the aqueous sol is adjusted such that an isoionic state results. In the course of this pH shift a precipitation of the active substance may occur.
It has turned out here that the particles do generally not exceed the colloidal or nanoparticulate size range.
The sol which has been thus prepared and adjusted to an isoionic state can be dried in a further process step. For this purpose, conventional drying methods, but preferably drying methods applying no or only little heat such as freeze drying, may be used.
Claims (14)
1. Solid pharmaceutical preparation comprising at least one at least partially charged active substance, which active substance is present in the form of a nanosol in which the active substance is bonded to an oppositely charged chitosan derivative, said solid pharmaceutical preparation being produced by a process, wherein - a chitosan derivative is selected according to the type and relative number of its charged groups and in coordination with the type and relative number of the charged groups of the active substance such that at a certain pH value an isoionic state or charge equalization between active substance and carrier can be achieved in the preparation, - an aqueous sol containing the active substance is prepared from the chitosan derivative, - the pH value of the aqueous sol is adjusted such that an isoionic state results, possibly with colloidal or nano-scale active substance particles precipitating, and - the thus-adjusted aqueous sol is dried.
2. Solid pharmaceutical preparation according to Claim 1, wherein the active substance possesses a positive charge and is bonded to a zwitterionic, acidic chitosan derivative.
3. Solid pharmaceutical preparation according to Claim 1, wherein the active substance possesses a negative charge and is bonded to a basic chitosan derivative.
4. Solid pharmaceutical preparation according to any one of claims 1 to 3, wherein the active substance and the chitosan derivative are present in the nanosol in isoionic state.
5. Solid pharmaceutical preparation according to any one of claims 1 to 4, wherein the active substance is present in the nanosol in colloidal or in nanoparticulate form.
6. Solid pharmaceutical preparation according to any one of claims 1 to 5, wherein the active substance is poorly soluble.
7. Solid pharmaceutical preparation according to any one of claims 1 to 6, wherein it contains a further polymeric carrier substance apart from the chitosan derivative.
8. Use of a pharmaceutical preparation according to any one of claims 1 to 7 for the production of a medicinal product.
9. Use of a pharmaceutical preparation according to Claim 8 for the production of a medicinal product for peroral application.
10. Use of a pharmaceutical preparation according to any one of Claims 8 or 9 for the production of a medicinal product that is administered as a powder, granulate, tablet or capsule.
11. Use of a pharmaceutical preparation according to any one of Claims 8 to 10 for the production of a medicinal product which, for the purpose of administration, is dissolved or redispersed in a liquid.
12. Use of a pharmaceutical preparation according to any one of Claims 8 to 11 for the production of a medicinal product having controlled active substance release.
13. Use of a pharmaceutical preparation according to any one of Claims 1 to 7 for the production of a diagnostic agent.
14. Process for the production of a pharmaceutical preparation according to any one of Claims 1 to 7, characterized in that a) a chitosan derivative is selected according to the type and relative number of its charged groups and in coordination with the type and relative number of the charged groups of the active substance such that at a certain pH value an isoionic state or charge equalization between active substance and carrier can be achieved in the preparation, b) an aqueous sol containing the active substance is prepared from the chitosan derivative, c) the pH value of the aqueous sol is adjusted such that an isoionic state results, possibly with colloidal or nano-scale active substance particles precipitating, and d) the thus-adjusted aqueous sol is dried.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19940794A DE19940794A1 (en) | 1999-08-27 | 1999-08-27 | Pharmaceutical preparation |
| DE19940794.0 | 1999-08-27 | ||
| PCT/EP2000/007904 WO2001015669A1 (en) | 1999-08-27 | 2000-08-14 | Pharmaceutical preparation containing nanosol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2382359A1 CA2382359A1 (en) | 2001-03-08 |
| CA2382359C true CA2382359C (en) | 2008-03-18 |
Family
ID=7919871
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002382359A Expired - Fee Related CA2382359C (en) | 1999-08-27 | 2000-08-14 | Pharmaceutical preparation containing nanosol |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP1206253B1 (en) |
| JP (1) | JP2003508423A (en) |
| KR (1) | KR100624499B1 (en) |
| CN (1) | CN1181815C (en) |
| AR (1) | AR025392A1 (en) |
| AT (1) | ATE279180T1 (en) |
| AU (1) | AU779692B2 (en) |
| BR (1) | BR0013563A (en) |
| CA (1) | CA2382359C (en) |
| CZ (1) | CZ301704B6 (en) |
| DE (2) | DE19940794A1 (en) |
| DK (1) | DK1206253T3 (en) |
| ES (1) | ES2231265T3 (en) |
| HK (1) | HK1047037B (en) |
| HU (1) | HU227609B1 (en) |
| IL (2) | IL148220A0 (en) |
| MX (1) | MXPA02002048A (en) |
| NZ (1) | NZ517541A (en) |
| PL (1) | PL203860B1 (en) |
| PT (1) | PT1206253E (en) |
| RU (1) | RU2256440C2 (en) |
| TR (1) | TR200200520T2 (en) |
| TW (1) | TWI267384B (en) |
| WO (1) | WO2001015669A1 (en) |
| ZA (1) | ZA200201135B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100638041B1 (en) * | 2003-12-24 | 2006-10-23 | 주식회사 삼양사 | A nanoparticle composition of a water-soluble drug for oral administration and a preparation method thereof |
| KR100767336B1 (en) * | 2006-04-19 | 2007-10-18 | 서평원 | Chitin/chitosan based functional organic-inorganic composite material and method for producing the same and use thereof |
| US9161901B2 (en) | 2008-02-21 | 2015-10-20 | University Of South Florida | Nanoparticle targeted drug delivery to the lungs using extra-testicular Sertoli cells |
| UA90013C2 (en) | 2008-03-19 | 2010-03-25 | Давид Анатолійович Нога | Pharmaceutical composition containing insulin and process for the preparation thereof |
| PL220269B1 (en) | 2008-04-21 | 2015-09-30 | Przedsiębiorstwo Produkcji Farmaceutycznej Hasco Lek Spółka Akcyjna | Composite carrier of powdered medicines, method of production the medicine carrier and equipment for production of particles of composite carrier |
| DE102009024542A1 (en) * | 2009-06-10 | 2010-12-16 | Arivine Pharma Ag | Compositions based on chitosan oligosaccharides |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5474989A (en) * | 1988-11-11 | 1995-12-12 | Kurita Water Industries, Ltd. | Drug composition |
| DE4140195C2 (en) * | 1991-12-05 | 1994-10-27 | Alfatec Pharma Gmbh | Pharmaceutical nanosol and process for its manufacture |
| US6184037B1 (en) * | 1996-05-17 | 2001-02-06 | Genemedicine, Inc. | Chitosan related compositions and methods for delivery of nucleic acids and oligonucleotides into a cell |
| CA2228251A1 (en) * | 1996-06-11 | 1997-12-18 | Zonagen, Inc. | Chitosan drug delivery system |
| ES2114502B1 (en) * | 1996-07-29 | 1999-07-01 | Univ Santiago Compostela | APPLICATION OF NANOPARTICLES BASED ON HYDROPHILIC POLYMERS AS PHARMACEUTICAL FORMS. |
| DE19845246A1 (en) * | 1997-12-18 | 1999-06-24 | Henkel Kgaa | Vitamin E compositions |
| WO1999036090A1 (en) * | 1998-01-16 | 1999-07-22 | The Johns Hopkins University | Oral delivery of nucleic acid vaccines by particulate complexes |
-
1999
- 1999-08-27 DE DE19940794A patent/DE19940794A1/en not_active Withdrawn
-
2000
- 2000-08-14 PL PL354572A patent/PL203860B1/en not_active IP Right Cessation
- 2000-08-14 NZ NZ517541A patent/NZ517541A/en not_active IP Right Cessation
- 2000-08-14 CN CNB008119031A patent/CN1181815C/en not_active Expired - Fee Related
- 2000-08-14 WO PCT/EP2000/007904 patent/WO2001015669A1/en active IP Right Grant
- 2000-08-14 PT PT00964016T patent/PT1206253E/en unknown
- 2000-08-14 CA CA002382359A patent/CA2382359C/en not_active Expired - Fee Related
- 2000-08-14 TR TR2002/00520T patent/TR200200520T2/en unknown
- 2000-08-14 JP JP2001519883A patent/JP2003508423A/en not_active Withdrawn
- 2000-08-14 RU RU2002103512/15A patent/RU2256440C2/en not_active IP Right Cessation
- 2000-08-14 KR KR1020027002507A patent/KR100624499B1/en not_active IP Right Cessation
- 2000-08-14 HU HU0300345A patent/HU227609B1/en not_active IP Right Cessation
- 2000-08-14 AT AT00964016T patent/ATE279180T1/en active
- 2000-08-14 IL IL14822000A patent/IL148220A0/en unknown
- 2000-08-14 BR BR0013563-1A patent/BR0013563A/en not_active IP Right Cessation
- 2000-08-14 EP EP00964016A patent/EP1206253B1/en not_active Expired - Lifetime
- 2000-08-14 MX MXPA02002048A patent/MXPA02002048A/en unknown
- 2000-08-14 DE DE2000508259 patent/DE50008259D1/en not_active Expired - Lifetime
- 2000-08-14 DK DK00964016T patent/DK1206253T3/en active
- 2000-08-14 AU AU75094/00A patent/AU779692B2/en not_active Ceased
- 2000-08-14 ES ES00964016T patent/ES2231265T3/en not_active Expired - Lifetime
- 2000-08-14 CZ CZ20020653A patent/CZ301704B6/en not_active IP Right Cessation
- 2000-08-25 TW TW089117149A patent/TWI267384B/en not_active IP Right Cessation
- 2000-08-25 AR ARP000104416A patent/AR025392A1/en not_active Application Discontinuation
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2002
- 2002-02-11 ZA ZA200201135A patent/ZA200201135B/en unknown
- 2002-02-18 IL IL148220A patent/IL148220A/en not_active IP Right Cessation
- 2002-11-22 HK HK02108480.8A patent/HK1047037B/en not_active IP Right Cessation
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| MKLA | Lapsed |
Effective date: 20130814 |