GB2084871A - An element containing a therapeutic or palliative agent - Google Patents

An element containing a therapeutic or palliative agent Download PDF

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GB2084871A
GB2084871A GB8127271A GB8127271A GB2084871A GB 2084871 A GB2084871 A GB 2084871A GB 8127271 A GB8127271 A GB 8127271A GB 8127271 A GB8127271 A GB 8127271A GB 2084871 A GB2084871 A GB 2084871A
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groups
gel chromatographic
polymer
chromatographic material
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/44Medicaments
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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 the non-active ingredient being a modifying agent
    • A61K47/56Medicinal 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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61Medicinal 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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0034Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A61K9/0036Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0048Eye, e.g. artificial tears
    • A61K9/0051Ocular inserts, ocular implants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007Drug-containing films, membranes or sheets
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/28Polysaccharides or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Reproductive Health (AREA)
  • Hematology (AREA)
  • Materials Engineering (AREA)
  • Urology & Nephrology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A solid or a semi-solid element, for example in the form of a membrane, a foil or a suppository contains one or more drugs. The element is made of a polymer comprising agar and/or agarose and/or a derivative or any one of these polymers, without any addition of a cross-linking agent. Particles of one or more cross-linked gel chromatographic materials are incorporated into the element, said gel chromatographic materials containing said one or more drugs.

Description

SPECIFICATION An element containing a therapeutic or palliative agent The present invention relates to a solid or semi-solid element containing one or more therapeutic or palliative agents, or some other medically active agent, all of which, for the sake of brevity, will hereinafter be termed "drugs". The invention also relates to a process for the production of such an element.
In treating many illnesses with an appropriate therapeutic or palliative agent, or with a combination of such agents, it is often difficult to maintain a desired even and sustained concentration of the drugs or drug. Often, when a drug is applied by intermittent dosing, that is to say when a predetermined dose is applied at regular intervals, e.g. every four hours, or twice a day, the concentration of the drug alternately fluctuates between a level which is too high and and a level which is too low in relation to the ideal treatment concentration.
Thus, if it is desired to maintain an adequate minimum concentration of a drug over a certain period of time, for example in treating an infection, when the drug is applied by intermittent doising a relatively large dose must be given to ensure that the concentration of the drug does not fall below the desired minimum level before the next dose is applied. This results in an over dosing, and also leads to a very high concentration of the drug just after the intermittent dose has been applied. Often this gives side-effects of varying degrees of undesirability.
Thus, there is a great need for a drug preparation which is capable of releasing drugs over a long period of time in a satisfactory concentration, so that a substantially uniform concentration of the drug can be maintained.
U.S.A. Patent Specification No. 3,867,519 discloses that a prior attempt has been made to satisfy this need by providing a device for example in the form of a thin sheet or roll.
The device is made of a polyelectrolyte crosslinked with a bivalent or polyvalent metal ion.
The device contains one or more more drugs.
These drugs can for example be enclosed by microcapsules which in their turn are incorporated in the device. The microcapsules are produced in a conventional way by coating the drug with a thin polymer layer. The device and the production thereof are connected with many drawbacks. For example, the device must be washed carefully after the crosslinking reaction. This often results in great losses of the drug from the device. Moreover, the device gives a poor degree of flexibility in respect of the release mechanism of the drug.
After the crosslinking reaction described in the U.S.A. Patent Specification the polymer will contain poisonous heavy metals, such as cadmium or barium. These metals are then released during the bio-erosion of the polymer, for example when the device is used to treat an unhealthy eye. This is clearly undersirable.
The present invention seeks to provide a device containing a drug which can release the drug over a long time in a therapeuically satisfactory manner so that appropriate concentrations of the drug can be maintained, and in which the above mentioned drawbacks of previously proposed arrangements are reduced or obviated.
According to one aspect of this invention there is provided a solid or a semi-solid element, containing one or more drugs, the element being made of a polymer comprising agar and/or agarose and/or a derivative of any one of these polymers, the element being made without any addition of a cross-linking agent, wherein particles of one or more crosslinked gel chromatographic materials are incorporated into the element, said gel chromatographic materials containing said one or more drugs.
The element may be in the form of a membrane or foil, or in the form of a pessary or other suppository.
Preferably the polymer of the element, as well as the gel-chromatographic material, contains one or more drugs.
In a preferred embodiment according to the invention the element is made of at least one of the polymers agar, agagrose or a derivative of any one of these. An especially good result is obtained if the polymer consists of agarose only, or if the polymer consists of agarose and/or a derivative thereof.
In another embodiment according to the invention the element is made of a mixture of at least one of the polymers agar, agarose or a derivative of any one of these and at least another polymer. The other polymer preferably contains hydroxyl groups.
Starch, dextran, cellulose, agaropectin or a derivative of any one of these can be mentioned as examples of suitably hydroxyl group containing polymers. However, it is to be understood that other hydroxyl group containing polymers can be used.
The element can advantageously contain functional groups, such as anionic or cationic groups. The anionic groups can, for example, consist of carboxy groups, sulphonic acid groups or phosphoric acid groups, while the cationic groups can, for example, consist of diethyl aminoethyl groups, ssmorfolino ethyl groups or d i-(hydroxylethyl)-a m inoethyl groups.
Advantageously the gel chromatographic material may consist of a cross-linked polymer which can contain hydroxyl groups, such as cross-linked polyvinyl alcohol or a cross-linked carbohydrate or a cross-linked derivative of either of these polymers. Cross-linked dextrin, starch, dextran, cellulose or a derivative of any one of these can be mentioned as examples of suitable carbohydrates.
Also other gel chromatographic materials, such as cross-linked polyacryl amide or polyvinyl pyrrolidone can be used. In certain cases, these polymers can also contain hydroxyl groups.
The gel chromatographic material itself can contain anionic or cationic groups. The anionic groups can for example consist of carboxy groups, sulphonic acid groups or phosphoric acid groups.
The cationic groups, on the other hand, can for example consist of diethyl aminoethyl groups, ssmorfolino ethyl groups or di-(hydroxethyl)-aminoethyl groups.
Many gel chromatographic materials are known per se, as shown for instance in the publication Gelchromatography by Determann (1967), British Patent Specifications No.
854,715 and 974,054, the U.S.A. Patent Specifications No. 3,277,025 and 3,275,576 and Swedish Patent Specifications No.
209,015 and 222,291.
Preferably the gel chromatographic material has an average particle size of 10-1000,um, for example 20-500 ym.
The particles of the gel chromatographic material can suitably be incorporated into the element by mixing them into the polymer used for the production of the device. The element can be produced by moulding, for instance.
The particles of the gel chromatographic material may contain a single drug or two or more different drugs. The drug or drugs can be incorporated into the gel chromatographic material in many different ways, such as absorption/adsorption, ion bonding, complex bonding or chemical bonding. The method chosen for incorporating any particular drug is firstly dependant on the physical and chemicai qualities of the drug, but also to a certain extent on how fast the drug should be released during use.
Usually, the gel chromatographic material can be adapted to the qualities of the drugs in a satisfactory way.
Separate gel chromatographic materials can be used for each drug, if desired, when more than one drug is to be incorporated in the element.
In one embodiment according to the invention, not only the gel chromatographic material, but also the element itself contains one or more drugs. These drugs can be incorporated into the material of the element in the same way as described above in connection with the incorporation of drugs into the gel chromatographic material.
Generally, the element may contain 75-99 per cent by weight of water when in a waterswollen state. When the element is to be used for the treatment of skin, wounds or mucous membranes it is especially preferred that the element is swollen in water or a physioligically acceptable sodium chloride solution. The element is so acceptable to the tissue in that state that it can be applied even in the ocular cavity and release drugs there, such as antibiotics or intraocular pressure decreasing agents, such as pilocarpine. Examples of other drugs which might be incorporated into the device are described in U.S.A. Patent Specification No. 3,867,519. Moreover, the element can contain spermicides, enzymes or prostacy dine.
By incorporating particles of a gel chromatographic material into an element according to the invention, the release velocity of the drugs can be regulated or selected in a satisfactory way.
The drugs must first leave the gel chromatographic material and then pass through the polymer of the element and finally enter a mucous membrane, for example, or other body site to be treated.
By choosing gel chromatographic materials with suitable impenetrability and diffusion properties, the release velocity for the drug can be selected to be at any desired level.
Furthermore, during the production of an element containing several different drugs, it is possible to incorporate a specific gel chromatographic materil for each drug. Then the different gel chromatographic materials can have the same or different impentrability and diffusion properties. Thus, it is possible to provide elements where different drugs are released at the same or at different velocities.
Of course, the proportion of drugs in the gel chromatographic material can be varied within wide limits depending on the kind of drug and the kind of gel chromatographic material.
It is envisaged that, in utilising the invention it will be possible to bring about extraordinary regulating conditions relating to the release velocity as well as to the proportion of a drug applied to a body site.
If the drug contains anionic or cationic groups, it is possible to further increase the ability of the device to bind and later release a larger amount of the drug, on condition that the gel chromatographic material contains ions of the opposite polarity, i.e. cationic and anionic ions respectively.
The release velocity of such ionically bonded drugs can be further regulated as compared to the other embodiments described above. Here the drugs will be released only after an ion exchange process where mainly sodium ions in liquid emanating from a wound or a mucous membrane have to pass first into and through the device and then into the particles of the gel chromatographic material. The drug in its turn must then diffuse through the gel chromatographic material and the device to finally enter the mucous membrane, for example.
The time needed for the drug to diffuse out of the particles of the cross-linked gel chromatographic material can also be prolonged by coating the particles with a thin sealing layer of a suitable material, such as polyvinyl pyrrolidone.
According to another aspect of this invention there is provided a process for the production of an element according to any one of the preceding claims wherein agar and/or agarose and/or a derivative of any one of these polymers, is dissolved or suspended in a water containing solvent, whereupon particles of one or more cross-linked gel chromatographic materials containing one or more drugs are mixed with the solution or suspension respectively, the mixture thus obtained being transformed to a solid or a semi-solid element, by applying it to a surface or introducing it into a mould, whereupon it is chilled or allowed to cool.
Preferably one or more further polymers are dissolved or suspended simultaneously with said polymers.
Advantageously, when the solution on the suspension is formed, heat is supplied to the water containing solvent.
The element obtained can for instance consist of a foil, or a membrane which in turn can be divided to a desired size, for example by cutting, or a pessary or other suppository. Of course, it is very rational to manufacture the foil, or the membrane, or the suppository by moulding, since such a method makes it possible to use a continuous manufacture. The division of the foil or the membrane to smaller pieces can also be made in a rational way.
Of course, it is possible according to the invention to make other devices than foils, membranes or suppositories. However, these devices have a very large field of application.
As mentioned above, the devices produced usually contain 75-99 per cent by weight of water when in a water-swollen state. Often they have that water content directly after production. Generally, a foil according to the invention having such a water content is soft, flexible and slippery. Often it is transparent. In a microscope one can easily see that the particles of gel chromatographic material are embedded in the polymer material constituting the foil itself.
The invention will be explained more in detail in connection with the embodiments described way of example below. Example 1 shows the production of a membrane in which gel chromatographic particles are embedded.
The particles contain the drug pilocarpine.
Example 2 also relates to the production of a membrane in which gel chromatographic particles are embedded. Then the particles contain iodine in a complex bonded state.
Example 3 shows the production of a cylindrical device in which gel chromatographic particles containing prostaglandin are incorpo rated. Example 4 relates to the production of a combination preparation in the form of a membrane, in which particles of two different gel chromatographic materials are incorpo rated. The first kind of gel chromatographic particles contains a local anaesthetic, while the other particles contain an inflammation damping drug. Moreover, the material of the device itself contains a local anaesthetic. Fi nally, Example 5 relates to the production of a membrane in which gel chromatographic par ticles containing an antibiotic are incorpo rated.
Example 1 A gel chromatographic material consisting of the sodium salt of carboxymethyl dextrin which had been produced from dextrin ac cording to the teaching of U.S.A. Patent Spe cification No. 3,277,025 and 3,25,576 had a gel bed volume of 6.5 ml/g and an ion exchanging capacity of 0.4 mekv/g in respect of carboxymethyl groups. Gel bed volume is the volume of the bed of gel formed by throughly soaking a specific weight of the drug material in water, and thus includes the volume of water clinging the exterior of the swollen granules of the material.
40 g of this gel material was transferred to a a nutsch funnel and treated with 400 ml 0.16 N hydrochloric acid in an aqueous solution containing 50% ethanol and 50% distilled water.
Then the gel was washed to neutral reaction with 400 ml of a mixture containing 50% ethanol and 50% distilled water.
The gel was sucked dry and then treated on the nutsch funnel with a solution of 10 g pilocarpine hydrochloride (Merck) in 200 ml of a mixture of 50% ethanol and 50% dis tilled water.
The gel was washed to neutral reaction with a solution consisting of 75% ethanol and 25% distilled water and then shrunk in 99.5% ethanol.
After being dried in a drying chamber at 75"C for 5 hours, 38 g of a dry powder having a nitrogen content of 0.34% was obtained.
A solution containing 4 g agarose (AGA ROSE A 37), INDUBIOSE, Pharmindustrie) (INDUBIOSE is a Trade Mark) in 100 g water was obtained by heating on a boiling water bath. Then the solution was chilled to 60"C, whereupon 5 g of the powder of the above gel chromatographic material containing ion bonded pilocarpine was added.
The suspension thus obtained was applied in a 3 mm thick layer on a glass plate. The suspension was allowed to cool to room tem perature. Then an element in the form of a transparent, soft, flexible and slippery mem brane was obtained. It could be cut into pieces of a desired form and size. In a microscope it could be established that the gel chromatographic particles containing ion bonded pilocarpine were moulded into the membrane.
The membrane produced was suitable for the treatment of glaucoma of the eye. In such treatment a piece of the membrane having a suitable size is placed under the uppe eyelid, and the pilocrpine will be gradually and successively released to the mucous membrane of the eye.
Example 2 An iodine containing, cross-linked gel chromatographic material, produced from sugar according to the teaching of Swedish Patent specification No. 405,680 had an iodine content of 1.11 %, an ion exchanging capacity of 0.92 mekv/g in respect of carboxymethyl groups in acid form, a gel bed volume of 7.3 ml/g and an average particle size size of 70 ,um.
3 g of this gel material was added, with stirring, to a solution having a temperature of 45"C and containing 6 9 agarose (Agarose A 37, Kebo 1.7539) in 100 ml distilled water.
The homogenous viscous suspension obtained was applied in a 2 mm thick even layer on a glass plate. The suspension as allowed to cool to 22"C. Then it was solidified to a membrane, which was found suitable for disinfection of skin and wound surfaces, for example.
Example 3 A prostaglandin containing, cross-linked gel chromatographic material made of hydroxye thyl cellulose according to the teaching of British patent application No. 80011 76 (British Patent Publication No. 2,041,220 A) had a gel bed volume of 5.3 ml/g and contained 0.35% prostaglandin (PGE2).
7 g of this gel material was added with stirring to a solution having a temperature of 44"C and consisting of 1.06 g agarose (Agarose A 37, INDUBIOSE, Pharmindustrie) (IN DUBIOSE is a Trade Mark) and 0.35 9 hydroxyethyl cellulose (Hydroxyäthylcellulose, Art 822068, Merck) in 50 ml distilled water.
The suspension thus obtained was formed into suppositories with a cylindrical shape, a diameter of 1 5 mm and a length of 30 mm by cooling in a mould. In this way 10 suppositories were obtained. 5 of them were freeze dried in a way known per se.
The suppositories were, whether they were freeze dried or not, intended for intravaginal application after an optional radiation sterilization. It is envisaged that they may be used for expediating the completion of pregnancy or for interruption pregnancy in connection with legal abortion.
Example 4 0.2 g lidocain (Lidocain, chloride anhydr.) was dissolved in 1 ml distilled water, whereupon the pH was adjusted to 6.5 by an addition of sodium hydrate.
The solution thus obtained was mixed with 2 g of a commercially available gel chromatographic material (SEPHADEX, G-25, Pharmacia Fine chemicals) (SEPHADEX is a Trade Mark) with a particle size of 20-80 ,um and a gel bed volume of 4.8 ml/g in water. The solution was allowed to diffuse into the gel chromatographic material with stirring, whereupon the product obtained was dried.
5 g of an inflammation damping drug (BET NOVAT, 0.1 per cent solution, Glaxo Laboratories Ltd) (BETNOVAT is a Trade Mark) was mixed with 2.5 g of a commercially available gel chromatographic material (SEPHADEX LH-20, Pharmacia Fine Chemicals) (SEPHA DEX is a Trade Mark) with an average particle size of 60 ,um and a gel bed volume of 4.1 ml/g.
The solution was allowed to diffuse into the gel chromatographic material with stirring, whereupon the product obtained was dried.
A solution containing 0.6 g agarose, (Agarose A 37, INDUBIOSE, Pharmindustrie) (IN DUBIOSE is a Trade Mark) in 20 ml of water was prepared by heating on a boiling water bath at stirring. The solution obtained was chilled to 45"C, whereupon the two products above were stirred down into the solution.
Then a solution of 0.2 g lidocain (Lidocain chloride anhydr.) in 1 ml distilled water was added. The pH of the solution had been adjusted to 6.5 by an addition of sodium hydrate. The suspension thus obtained was applied in a 2 mm thick layer on a glass plate and allowed to cool to 20"C. The membrane obtained could be cut into pieces and was suitable for example for treatment of painful and infected wounds.
Example 5 400 mg of an antibiotic (CHLOROMY CETIN, Parke-Davis, USA) (CHLOROMYCETIN is a Trade Mark) was dissolved in 8 ml distilled water. The solution thus obtained was added with stirring to 2.0 g gel chromatographic polyacryl amide gel (Biogel P-6, Bio-Rad Laboratories, USA) with an average particle size of 60 ljm. The product thus obtained was freeze dried in a way known per se.
A solution was prepared of 0.5 9 agarose (Agarose A 37, INDUBIOSE Pharmindustrie (INDUBIOSE is a Trade Mark) in 20 ml distilled water by heating on a boiling water bath with stirring.
The solution thus obtained was chilled to 46"C, whereupon the above product was mixed with the solution.
The suspension obtained was appled in a 2.5 mm thick layer on a glass plate and allowed to cool to 20"C. The solidified membrane could be cut into desired dimensions for treatment of wound infections and eye infections for example.
The present invention is not limited to the embodiments shown, since these can be modified in different ways within the scope of the present invention.

Claims (1)

1. A solid or a semi-solid element, containing one or more drugs, the element being made of a polymer comprising agar and/or agarose and/or a derivative of any one of these polymers, the element being made without any addition of a cross-linking agent, wherein particles of one or more crosslinked gel chromatographic materials are incorporated into the element, said gel chromatographic materials containing said one or more drugs.
2. An element according to claim 1 in the form of a membrane of foil.
3. An element according to claim 1 in the form of a pessary or other suppository.
4. An element according to any one of the preceding claims wherein the polymer of the element contains one or more drugs as well as the gel chromatographic material.
5. An element according to any one of the preceding claims made of a mixture of agar and/or agarose and/or a derivative of any one of these polymers and at least one other polymer.
6. An element according to claim 5, wherein said other polymer is a hydroxyl group containing polymer.
7. An element according to claim 6, wherein the hydroxyl group containing polymer consists of starch, dextran, cellulose, agaropectin or a derivative of any one of these polymers.
8. An element according to any one of claims 1 to 4 wherein the polymer comprises solely agarose and/or a derivative thereof.
9. An eleent according to any one of the preceding claims which contains functional groups, in the form of anionic or caionic groups.
10. An element according to claim 10, wherein the anionic groups consist of carboxy groups, sulphonic acid groups and/or phosphoric acid groups.
11. An element according to claim 10, wherein the cationic groups consist of diethyl aminoethyl groups, ssmorfolinio ethyl groups and/or di-(hydroxyethyl)-aminoethyl groups.
1 2. An element according to any one of the preceding claims wherein the gel chromatographic material consists of a cross-linked polymer.
1 3. An element according to claim 12, wherein the gel chromatographic material consists of a cross-linked hydroxyl group containing polymer.
14. An element according to claim 1 3 wherein said polymer is polyvinyl alcohol, a carbohydrate or a derivative thereof.
1 5. An element according to claim 1 3 or 14 wherein the gel chromatographic material consists of cross-linked dextrin, starch, dextran, cellulose or a derivative of any one of these materials.
16. An element according to claim 12 or 1 3 wherein the gel chromatographic material consists of cross-linked polyacryl amide or polyvinyl pyrrolidone.
1 7. An element according to any one of the preceding claims wherein the gel chromatographic material contains anionic or cationic groups.
1 8. An element according to claim 1 7 wherein the anionic groups consist of carboxy groups, sulphonic acid groups or phosphoric acid groups.
1 9. An element according to claim 17, wherein the cationic groups consist for example of diethyle aminoethyl groups, ssmorfolino ethyl groups or di-(hydroxyethyl)-aminoethyl groups.
20. An element according to any one of the preceding claims wherein the gel chromatographic material has an average particle size of 10-10001sm.
21. An element according to claim 20 wherein the gel chromatographic material has an average particle size of 20-500 ym.
22. An element according to any one of the preceding claims wherein the particles of the gel chromatographic material are moulded into the element.
23. An element according to any one of the preceding claims when in a water swollen state and which contains 75-99 per cent by weight of water.
24. A process for the production of an element according to any one of the preceding claims wherein agar and/or agarose and/or a derivative of any one of these polymers, is dissolved or suspended in a water containing solvent, whereupon particles of one or more cross-linked gel chromatographic materials containing one or more drugs are mixed with the solution or suspension respectively, the mixture thus obtained being transformed to a solid or a semi-solid element, by applying it to a surface or introducing it into a mould, whereupon it is chilled or allowed to cool.
25. A process according to claim 24 wherein one or more further polymers are dissolved or suspended simultaneously with said polymers.
26. A process according to claim 24 or 25 wherein when the solution or the suspension is formed, heat is supplied to the water containing solvent.
27. An element according to claim 1 and substantially as herein described.
28. An element according to claim 1 and substantially as herein described with reference to Example 1.
29. An element according to claim 1 and substantially as herein described with reference to the Example 2.
30. An element according to claim 1 and substantially as herein described with reference to Example 3.
31. An element according to claim 1 and substantially as herein described with reference to Example 4.
32. An element according to claim 1 and substantially as herein described with reference to Example 5.
33. A process according to claim 24 and substantially as herein described.
34. A process according to claim 24 and substantially as herein described with reference to Example 1.
35. A process according to claim 24 and substantially as herein described with reference to Example 2.
36. A process according to claim 24 and substantially as herein described with reference to Example 3.
37. A process according to claim 24 and substantially as herein described with reference to Example 5.
38. An element whenever produced by the process of any one of claims 24 to 26 or 33 to 38.
40. Any novel feature or combination of feature disclosed herein.
GB8127271A 1980-09-10 1981-09-09 An element containing a therapeutic or palliative agent Expired GB2084871B (en)

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SE8006300 1980-09-10

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GB2084871A true GB2084871A (en) 1982-04-21
GB2084871B GB2084871B (en) 1984-08-08

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JP (1) JPS5780313A (en)
CH (1) CH650924A5 (en)
DE (1) DE3135917A1 (en)
FR (1) FR2489693B1 (en)
GB (1) GB2084871B (en)
SE (1) SE448203B (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2126086A (en) * 1982-08-24 1984-03-21 Cilag Ag Medicated suppository containing gel-forming and gel-dispersing agents
WO2001001950A1 (en) * 1999-07-06 2001-01-11 The Procter & Gamble Company Pre-formed gel sheet
WO2004014350A2 (en) * 2002-08-13 2004-02-19 Sirus Pharmaceuticals Ltd Polymer conjugates of a local anaesthetic drug
WO2009153798A1 (en) * 2008-06-16 2009-12-23 Natco Pharma Limited Cross-linked dextrin as a tablet disintegrant/excipient

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2174538A1 (en) * 1993-10-22 1995-04-27 Michio Nagasawa Base for sustained-release preparation, sustained-release preparation, and process for producing the preparation
DE4445003A1 (en) * 1994-12-16 1996-06-20 Fhw Feucht Hygiene Werk Gmbh Agent for disinfecting wounds
DE19819652A1 (en) * 1998-05-02 1999-11-11 Lohmann Therapie Syst Lts Therapeutic system for topical or transmucosal application of at least one care or active ingredient to or through the nasal mucosa, as well as method for application of the system

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3867519A (en) * 1972-04-27 1975-02-18 Alza Corp Bioerodible drug delivery device
US3845770A (en) * 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
GB1594389A (en) * 1977-06-03 1981-07-30 Max Planck Gesellschaft Dressing material for wounds
AT371723B (en) * 1978-11-15 1983-07-25 Max Planck Gesellschaft TRANSPARENT LIQUID BANDAGE MATERIAL, AND METHOD FOR THE PRODUCTION THEREOF

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2126086A (en) * 1982-08-24 1984-03-21 Cilag Ag Medicated suppository containing gel-forming and gel-dispersing agents
WO2001001950A1 (en) * 1999-07-06 2001-01-11 The Procter & Gamble Company Pre-formed gel sheet
WO2004014350A2 (en) * 2002-08-13 2004-02-19 Sirus Pharmaceuticals Ltd Polymer conjugates of a local anaesthetic drug
WO2004014350A3 (en) * 2002-08-13 2004-10-07 Sirus Pharmaceuticals Ltd Polymer conjugates of a local anaesthetic drug
WO2009153798A1 (en) * 2008-06-16 2009-12-23 Natco Pharma Limited Cross-linked dextrin as a tablet disintegrant/excipient

Also Published As

Publication number Publication date
GB2084871B (en) 1984-08-08
SE8105134L (en) 1982-03-11
DE3135917A1 (en) 1982-05-27
FR2489693B1 (en) 1986-05-09
FR2489693A1 (en) 1982-03-12
SE448203B (en) 1987-02-02
CH650924A5 (en) 1985-08-30
JPS5780313A (en) 1982-05-19

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