CA1225595A - Hydrogel-containing envelopes - Google Patents
Hydrogel-containing envelopesInfo
- Publication number
- CA1225595A CA1225595A CA000448619A CA448619A CA1225595A CA 1225595 A CA1225595 A CA 1225595A CA 000448619 A CA000448619 A CA 000448619A CA 448619 A CA448619 A CA 448619A CA 1225595 A CA1225595 A CA 1225595A
- Authority
- CA
- Canada
- Prior art keywords
- envelope
- hydrogel
- water
- swollen
- tube
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/009—Sachets, pouches characterised by the material or function of the envelope
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- C—CHEMISTRY; METALLURGY
- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F1/00—Treatment of water, waste water, or sewage
- C02F1/26—Treatment of water, waste water, or sewage by extraction
- C02F1/265—Desalination
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/48—Polyethers
- C08G18/4833—Polyethers containing oxyethylene units
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
- C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52
- C08G18/6666—Compounds of group C08G18/48 or C08G18/52
- C08G18/667—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38
- C08G18/6674—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/3203
- C08G18/6677—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/3203 having at least three hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2210/00—Compositions for preparing hydrogels
Abstract
C A N A D A
S P E C I F I C A T I O N
TO ALL WHOM IT MAY CONCERN:
Be it known that I, NEIL BONNETTE GRAHAM, a dual U.K. and Canadian Citizen of 6, Kilmardinny Grove, Bearsden, Glasgow, Scotland G61 3NY have invented certain new and useful improvement in HYDROGEL-CONTAINING ENVELOPES
and the following disclosure contains a full description of the invention and of the best mode known to the inventor for taking advantage of same.
ABSTRACT OF DISCLOSURE
An envelope having flexible water-permeable or porous walls contains a quantity of particulate water-insoluble hydrogel. The quantity of hydrogel in the envelope is such that, when the hydrogel is fully swollen at 20°C, its volume is at least 66%, preferably at least 100%, of the maximum non-stretched internal volume of the envelope. Thus, the envelope according to the invention is limp and floppy under dry conditions but in a wet environment the hydrogel absorbs water and sells accordingly causing the envelope to swell and take on a more rigid configuration. The envelope is particularly useful for the administration of sustained release pharmaceutically or veterinarily active ingredients.
Thus the limp dry envelope may for example be rolled up for introduction through the throat but will swell up and therefore be retained in the stomach for sustained release of the active ingredient therein.
S P E C I F I C A T I O N
TO ALL WHOM IT MAY CONCERN:
Be it known that I, NEIL BONNETTE GRAHAM, a dual U.K. and Canadian Citizen of 6, Kilmardinny Grove, Bearsden, Glasgow, Scotland G61 3NY have invented certain new and useful improvement in HYDROGEL-CONTAINING ENVELOPES
and the following disclosure contains a full description of the invention and of the best mode known to the inventor for taking advantage of same.
ABSTRACT OF DISCLOSURE
An envelope having flexible water-permeable or porous walls contains a quantity of particulate water-insoluble hydrogel. The quantity of hydrogel in the envelope is such that, when the hydrogel is fully swollen at 20°C, its volume is at least 66%, preferably at least 100%, of the maximum non-stretched internal volume of the envelope. Thus, the envelope according to the invention is limp and floppy under dry conditions but in a wet environment the hydrogel absorbs water and sells accordingly causing the envelope to swell and take on a more rigid configuration. The envelope is particularly useful for the administration of sustained release pharmaceutically or veterinarily active ingredients.
Thus the limp dry envelope may for example be rolled up for introduction through the throat but will swell up and therefore be retained in the stomach for sustained release of the active ingredient therein.
Description
~2~5595 - This invention relates to hydrogel containing envelopes.
Hydrogels are swellable by a~ueous media and -thei.r use as absorbents of wa-ter or water vapour is well known. Thus for example granules o~ hydrogelS
either free or in a water-permeable or porous bag7 may be placed in containers for apparatus. The hydrogel gr~lules absorb any water or water vapo~u~
entering the container and thus maintain a dry atmosphere for the apparatus therein~ ther hydrogels may be used as absorbents in articles of personal hygiene, ~or example tampons, incontinence pads, diapers as suggested in Bri-tish Patent Specification No: 2100269A.
In addi-tion it is known to use hydrogels as carriers, excipîents, or delivery agents fol active~
e.g. pharmaceutical, veterinary9 ingrediell-tsO ThPre are many treatments where sustained release of ac~ive ingredient ~rom ~or ext~1ple orally admin.is-tered pharmaceutical or ve-terinary compositions is desirablt?0 There has been mvch in-terest in the use of hydrogels in the prepara-tion of sustained release com~ositions whereby the active ingredient is released grad~ally from the composi-tion. Thus UrSo Patent Specifications Nos: 3551556 and 3689634 describe .sustaiiled release dr~-containing com.positions colllprisil~ ~he dlu~ a~
Hydrogels are swellable by a~ueous media and -thei.r use as absorbents of wa-ter or water vapour is well known. Thus for example granules o~ hydrogelS
either free or in a water-permeable or porous bag7 may be placed in containers for apparatus. The hydrogel gr~lules absorb any water or water vapo~u~
entering the container and thus maintain a dry atmosphere for the apparatus therein~ ther hydrogels may be used as absorbents in articles of personal hygiene, ~or example tampons, incontinence pads, diapers as suggested in Bri-tish Patent Specification No: 2100269A.
In addi-tion it is known to use hydrogels as carriers, excipîents, or delivery agents fol active~
e.g. pharmaceutical, veterinary9 ingrediell-tsO ThPre are many treatments where sustained release of ac~ive ingredient ~rom ~or ext~1ple orally admin.is-tered pharmaceutical or ve-terinary compositions is desirablt?0 There has been mvch in-terest in the use of hydrogels in the prepara-tion of sustained release com~ositions whereby the active ingredient is released grad~ally from the composi-tion. Thus UrSo Patent Specifications Nos: 3551556 and 3689634 describe .sustaiiled release dr~-containing com.positions colllprisil~ ~he dlu~ a~
- 2 - 122~i5~5 a hydrogel through which the dru~ is released. U.S0 Patent Speci:Eication ~lo: 4~4049~ describes a pouch for the con~rolled release OI ac-l;ive ingredie~lt, in this case principally of ingredien-t for swimming-5 pool chlorination, wherein the pouch cornprise s asealed envelope of wa-ter-insolvhle pol~vinyl alcohol hydrogel. ~he e.g. chlorina-tio-n agen~t is ~tlîus released through t~e hydrogel walls of the pouch envelope o~rer a long period OI time when the pouch 10 is immersed in water. Sus-tained release prepara~tions comprising an active ingredien-t and a hydrogel have also been described in Bri-tish Patent Speciîications Nos: 2047093A, 2047094A, 209026L~A and 2108517A.
Also in the generally medical field i-t is known 15 to use hydrogels in wound dressings, where -the hydrogels are applied over the wounds to protect tl~em from the external en~,-ironment. Suitable hydrogels for use in wound dressings are described for example in G~B~ 2108517A. Also Europec~n Patent Specification 20 No: 00~1018 (~1) describes covering materi~l for, for example ~ wound, wherein a slab of swollen hydrogel material is provided, at least on the side to be in contac-t with the wound, wi-~h a permeable membrane. In wound dressings o:E -this type wound 25 exudate is absorbed by the hydro~el.
It has now been îound that considerable benei~its to different applications may be` obtaine~ b~ having a particulate hydrogel contained in an e~lve:lope~ and having a par-ticular mechanical relation~ ip bet~een 30 the extern~ .olume OI -the swollen hydrogel alld i~le in-ternal volume o~ the envelope.
According to the pre sent inventio thel e is provided an en~elope having :Elexi~le, ~Ya-ter-permea~le or porous walls and a ~ivell max:Lmum non-s-tretclled 35 internal ~ une and collt~inily~; a quantit~ o~
particulat.e water~inso`luble hydrogel :in ~ close~
Also in the generally medical field i-t is known 15 to use hydrogels in wound dressings, where -the hydrogels are applied over the wounds to protect tl~em from the external en~,-ironment. Suitable hydrogels for use in wound dressings are described for example in G~B~ 2108517A. Also Europec~n Patent Specification 20 No: 00~1018 (~1) describes covering materi~l for, for example ~ wound, wherein a slab of swollen hydrogel material is provided, at least on the side to be in contac-t with the wound, wi-~h a permeable membrane. In wound dressings o:E -this type wound 25 exudate is absorbed by the hydro~el.
It has now been îound that considerable benei~its to different applications may be` obtaine~ b~ having a particulate hydrogel contained in an e~lve:lope~ and having a par-ticular mechanical relation~ ip bet~een 30 the extern~ .olume OI -the swollen hydrogel alld i~le in-ternal volume o~ the envelope.
According to the pre sent inventio thel e is provided an en~elope having :Elexi~le, ~Ya-ter-permea~le or porous walls and a ~ivell max:Lmum non-s-tretclled 35 internal ~ une and collt~inily~; a quantit~ o~
particulat.e water~inso`luble hydrogel :in ~ close~
3 ~2~55~35 envelope ~7herein ~he volume of the ~U~ltity of hydrogel when ~llly swollen at 20C amounts -to at least 65% o~ the given maximum non-stretched internal volume of the envelope but is insufficient when f~l y swollen at 20C -to rupture the envelope.
The "m~xin~um non-s-tretched internal volume"
of the envelope according to the presen:~ i~vention is the maximum internal volume of the envelope before the walls of the envelope s-tart s-tretching.
~en a flexible-walled envelope is flat it has an internal volume of substantially zero. As material is in-troduced into the envelope, e.g. by inf]a-tion, the internal volume of the envelope will increase~
without stretchin~ of`-~le enve]ope walls, to a maximum. Beyond this maximum non-stretched i~ternal volume any further increase in the internal volume of the envelope involves stretching o the material of the envelope walls. Even-tually, of course9 if too much internal pressure is applied the envelope walls will rupture~
When the hydrogel used according to -the present invention contacts water (in liquid or vapour form), it absorbs the water and the hydrogel is thereby caused to swell. According to the presel~t invention the quantity of hydrogel present in the envelope is such that, when f~lly swollen at 20~ 9 its volun~e amoun-ts to at least 66% of -the maximum non-stretched internal vol~ne of the ellvelope.
Preferably the fully swollen volume of the hydrog~l amounts to at least 100~S of the maximum non-stretched internal vol~ne of the envelope. Th~, when the hydrogel is presen-t in -the ~lvelope in a non-f~lly swollen s-tate the en~elope is a limp, flexible structure. As the hydrogel ahsol~bs wa-ter -throu~l -the ~Yater-permeable or porous ~alls of -the envelope, the hydrogel s~Yells within -~le
The "m~xin~um non-s-tretched internal volume"
of the envelope according to the presen:~ i~vention is the maximum internal volume of the envelope before the walls of the envelope s-tart s-tretching.
~en a flexible-walled envelope is flat it has an internal volume of substantially zero. As material is in-troduced into the envelope, e.g. by inf]a-tion, the internal volume of the envelope will increase~
without stretchin~ of`-~le enve]ope walls, to a maximum. Beyond this maximum non-stretched i~ternal volume any further increase in the internal volume of the envelope involves stretching o the material of the envelope walls. Even-tually, of course9 if too much internal pressure is applied the envelope walls will rupture~
When the hydrogel used according to -the present invention contacts water (in liquid or vapour form), it absorbs the water and the hydrogel is thereby caused to swell. According to the presel~t invention the quantity of hydrogel present in the envelope is such that, when f~lly swollen at 20~ 9 its volun~e amoun-ts to at least 66% of -the maximum non-stretched internal vol~ne of the ellvelope.
Preferably the fully swollen volume of the hydrog~l amounts to at least 100~S of the maximum non-stretched internal vol~ne of the envelope. Th~, when the hydrogel is presen-t in -the ~lvelope in a non-f~lly swollen s-tate the en~elope is a limp, flexible structure. As the hydrogel ahsol~bs wa-ter -throu~l -the ~Yater-permeable or porous ~alls of -the envelope, the hydrogel s~Yells within -~le
4 ~22~595 envelope and the envèlope becomes inflated and more rigid.
When the volume of the ~ully swollen hydrogel amounts to the minimum 66% of the maximum non stretched internal volume of the envelope even ~7hen the hydrogel is fully swollen the envelope accordir~
to the prese~lt invention will not be fully rigid thou~1 it will be substantially more rigid and of greater size than the non-~ully swollen version.
Preferably though, as mentioned above, the fully swollen hydrogel should have a volume amounting to at least 100% of -the m~ximum non-stre-tched internal volume of the envelope. In this way, when the hydrogel has swollen, the envelope according to the present invention has substan-tiall~r its maximum volume. The rigidity of the envelope will increase as the internal pressure of the envelope increases, though of course the degree of swelling should not be so great that the envelope itself is ruptured.
The envelope according to the present invention has different uses. For example the envelope may be used as an absorbent of liquid water or of water vapour, particularly in locations where the presence of such water is deleterious. Thus for example in homes where condensation occurs or in cars where drips tend to occur envelopes according to the invention, generally in long strip form, can be placed e.g. below the windows prone to condensation to absorb water. ~s the water is absorbed by the hydrogel, the hydrogel will swell and accordil~gly the envelope increase in size though it will remain dry to the touch. It can readily be seen when the envelope is ~ully swollen and thus will no longer absorb ~urther water by the more rigid, infla-ted (sausage-like) ~ppearance of -the envelope. The envelope can thensimply be removed ~nd replaced by
When the volume of the ~ully swollen hydrogel amounts to the minimum 66% of the maximum non stretched internal volume of the envelope even ~7hen the hydrogel is fully swollen the envelope accordir~
to the prese~lt invention will not be fully rigid thou~1 it will be substantially more rigid and of greater size than the non-~ully swollen version.
Preferably though, as mentioned above, the fully swollen hydrogel should have a volume amounting to at least 100% of -the m~ximum non-stre-tched internal volume of the envelope. In this way, when the hydrogel has swollen, the envelope according to the present invention has substan-tiall~r its maximum volume. The rigidity of the envelope will increase as the internal pressure of the envelope increases, though of course the degree of swelling should not be so great that the envelope itself is ruptured.
The envelope according to the present invention has different uses. For example the envelope may be used as an absorbent of liquid water or of water vapour, particularly in locations where the presence of such water is deleterious. Thus for example in homes where condensation occurs or in cars where drips tend to occur envelopes according to the invention, generally in long strip form, can be placed e.g. below the windows prone to condensation to absorb water. ~s the water is absorbed by the hydrogel, the hydrogel will swell and accordil~gly the envelope increase in size though it will remain dry to the touch. It can readily be seen when the envelope is ~ully swollen and thus will no longer absorb ~urther water by the more rigid, infla-ted (sausage-like) ~ppearance of -the envelope. The envelope can thensimply be removed ~nd replaced by
- 5 ~225595 a fresh one if there remains unabsorbed water.
The removed ~ully swollen envelope can be heated, e.g. over a radiator~ whic~ ~ill cause the water to be desorbed ~y the hydrogel. The envelope will thus be returned to its limp~ ~lexible ~orm ready for reuse. Alternatively l~he fully swollen envelope can simply be left because reduc~ion in the humidity of the atmosphere, as tends to occur during the day, will also cause wa-ter to be desorbed by the hydrogel making it ready for reuse.
In a similar way the envelopes of the present invention can be used to absorb water v~pour L rom the atmosphere e.g. with a view to preventing condensation occurring again for example in the home or in cars or in ships in dry dock. The envelopes will absorb water vapour from the atmosphere where -there is high humidity and it will be desorbed when the humidity is reduced or the heat is increased.
The increase in size and/or rigidity of the envelope according to the presen-t invention as ~a~er is absorbed is a function of the degree of swelli~g a~d therefore this can be used as a measure of -the amount of water absorbed by the hydrogel. The swellin~ oî the envelopes according to -the present inverltion can for example be used to provide a warning that liquid or vapour water levels are rising too high in a particular location ~hus -the osmotic pressure whicll builds up in -the envelope according~ to the presellt invention as -the hydl~gel swells can be used to exert pressure to ac-tuate e.g. an alarm mechanism when this pressure exceeds tha-t correspondir~ to -the sa~e liquid or vapo~u~
water levels in the part:icular loc~ationO
With sui-kable shapi~ tne en~relopes accor~ing to ~he preserit inverl-tion may- be used as ar-ticles o
The removed ~ully swollen envelope can be heated, e.g. over a radiator~ whic~ ~ill cause the water to be desorbed ~y the hydrogel. The envelope will thus be returned to its limp~ ~lexible ~orm ready for reuse. Alternatively l~he fully swollen envelope can simply be left because reduc~ion in the humidity of the atmosphere, as tends to occur during the day, will also cause wa-ter to be desorbed by the hydrogel making it ready for reuse.
In a similar way the envelopes of the present invention can be used to absorb water v~pour L rom the atmosphere e.g. with a view to preventing condensation occurring again for example in the home or in cars or in ships in dry dock. The envelopes will absorb water vapour from the atmosphere where -there is high humidity and it will be desorbed when the humidity is reduced or the heat is increased.
The increase in size and/or rigidity of the envelope according to the presen-t invention as ~a~er is absorbed is a function of the degree of swelli~g a~d therefore this can be used as a measure of -the amount of water absorbed by the hydrogel. The swellin~ oî the envelopes according to -the present inverltion can for example be used to provide a warning that liquid or vapour water levels are rising too high in a particular location ~hus -the osmotic pressure whicll builds up in -the envelope according~ to the presellt invention as -the hydl~gel swells can be used to exert pressure to ac-tuate e.g. an alarm mechanism when this pressure exceeds tha-t correspondir~ to -the sa~e liquid or vapo~u~
water levels in the part:icular loc~ationO
With sui-kable shapi~ tne en~relopes accor~ing to ~he preserit inverl-tion may- be used as ar-ticles o
- 6 -- l22 5~gS
person~l hygiene. They could be used by incontinent persons or as tampons or absorbing pads Gr as sweat bands. With the mechanical relationship of envelope and swollen hydrogel size according to the present invention, the user is readily able to detect by the swollen, i-nflated nature of the article according to the invention when the article will no longer absorb further although it is still dry to the feel and accordingly when it should-be replaced. This is advantageous for example for reasons of comfort.
The envelopes according -to the present invention may further be used for the removal of water ~rom mixtures of non-aqueous liquids such as lubricating oils and many organic solvents whereby the water will be absorbed from the mixture to leave the non-aqueous liquid. Using the envelope according to the invention, it can readily be detected by the swollen state of the envelope that it is saturated and needs to be replaced for removal of further water.
In addition to absorbing water vapour from places o~ high humidity, the envelopes according to the present invention can also be used for humidification in places of low humidity. Thus there can be used a fully inflated envelope according to the present invention wherein the hydrogel is in the fully swollen state. In places of 122~i595
person~l hygiene. They could be used by incontinent persons or as tampons or absorbing pads Gr as sweat bands. With the mechanical relationship of envelope and swollen hydrogel size according to the present invention, the user is readily able to detect by the swollen, i-nflated nature of the article according to the invention when the article will no longer absorb further although it is still dry to the feel and accordingly when it should-be replaced. This is advantageous for example for reasons of comfort.
The envelopes according -to the present invention may further be used for the removal of water ~rom mixtures of non-aqueous liquids such as lubricating oils and many organic solvents whereby the water will be absorbed from the mixture to leave the non-aqueous liquid. Using the envelope according to the invention, it can readily be detected by the swollen state of the envelope that it is saturated and needs to be replaced for removal of further water.
In addition to absorbing water vapour from places o~ high humidity, the envelopes according to the present invention can also be used for humidification in places of low humidity. Thus there can be used a fully inflated envelope according to the present invention wherein the hydrogel is in the fully swollen state. In places of 122~i595
- 7 -low humidity water will be desorbed from -~he hydrogel and go into the atmosphere. For this use it is the return of the envelope to its limp, ~loppy state which indicates tha-t replacement is required. The return to the limp,floppy state shows that the water has been desorbed and accordingly that the envelope is no longer actillg as a humidifier.
Because the envelopes according to the present invention are limp and flexible in the subs-tantially dry, non-swollen state while being inflated and substantially rigid in the fully swollen state, they can be introduced into and then be retained in a cavity or container having a narrow entrance and exit. Thus the envelope can be rolled up if necessary to introduce it into the cavity or containe-r and, as long as the cavity or container has sufficient water therein, inside the hydrogel will swell causing the envelope to inflate to a rigid structure so that it is too lar~e to leave via either the -narrow entrance or the narrow exit. This is of particular interest in the veterinary and pharmaceutical fields.
Thus the envelopes according -to the presen-t invention may be used in the veterinary and pharmaceu3tical fields; particularly for the administration of sustained release compositions _ 8 - 1225595 to animals and human beings. It is of course well known to administer veterinarily, pharmaceutically or biologically active ingredients which are released within the animal or human being over an extended period of time following administration. Gne of the problems associated with such compositions is the ensuring that tlley are retained within the stomach for a sufficient length of time. Various compiicated devices have been proposed to ensure adequate retention in the stomach. Further, while this may not be a problem with animals for slaughter, especially with human patients, it is desirable that the device should, after all the active ingredient has been used up, be itself discharged from the stomach.
Suitable veterinarily active ingredients include antiinfective agents e.g. bacteriorcides, such as anti-biotics and viruscides: anti-parasitic agents e.q.
nematicides: oral vacines: and growth-promoting agents e.g. anabolics, trace elements and vitamins. Trace element preparations may include one or more of magnesium, iron, iodine, copper, cobalt, manganese, zinc and selenium, es~ecially copper, cobalt, selenium or iodine.
Accordingly the present invention also provides ~5 an envelope having flexible, water-permeable or porous walls ~nd a given r.~ximum non-stretched internal volur.le and contai-ning a quantity of particulate water-insoluble hydrogel an~ a pharm~ceutically, veterinarily or biologically active ingredient in sustained release form in the closed e~velope wherein the v~lume of the quantity of hydrogel when fully swollen at 20C amoun~s to at least 66% of the given maximum non-stretched internal volume but is insufficient when ~ully swollen at 20C to rupture the envelope, -9 12~i59~
This envelope, in the non-swollen state, can simply be rolled up if necessary and swallowed by the patient or ~orced down the throat of an a~imal being treated by a conventional means such as a bolus gun. In the stomach water traversing the water-permeable or porous ~lalls of the envelope will be absorbed by the hydrogel from the stomach juices and accordingly the envelope will swell up in the s~omach to its inflated form. Accordingly there it will be retained within the stomach during the sustained release of the active ingredient. mus the present invention offers a very simple solution to the problem of retention of sust~ined release compositions in the stomach.
15 ~~~ It may be convenient in some applications, ~or ease of administration, to have the envelope contained in a second outer package which provides some rigidity to the unswollen floppy form of the device. This outer package can ease administration by making it more easy 20 to swallow. The outer package subsequently ruptures by degradation of its adhesive, stitching or of its material or merely under the pressure exerted by the envelope when it swells inside. For example a paper tube, a collagen skin or a plastics film with protein adhesive 25 all provide suitable exteriors to enable the devices to be swallowed or placed in position more easily Envelopes according to the present illvention can also be used as slimming aids. Thus the envelopes, ~Yhich in t~is case need not con~ain any 30 pharmaceutically active ingredient, can be s~lall~wed by someone wanting to slim. T~R envelope will swell and be retained in the human stomach to provide a feeling of fuIlness and thus reduce appetite.
12~5595 A yet further application of the present invention is in the providing of self-erecting three dimensional structures. These structures may be of any desired shape. The structures can comprise a single envelope according to the invention or can comprise a plurality of compartments joined together, each compartment having a given maximum non-stretched internal volume and containing a quantity of particulate water-insoluble hydrogel wherein the volume of thQ auantity of hydrogel when fully swollen at 20C amounts to at least 66SS, preferably at least 100%, of the given maximuril non-stretched internal volume but is insufficient when fully swollen at 20~C to rupture the compartment.
These structures will be self-erecting when wetted, e.g. in the rain or by immersing or spraying with water. In this way large rigid structures may be obtained. Of course the structures according to the present invention have to be maintained in wet conditions if they are to stay sufficiently rigid.
Thus they will generally be used for the rapid erection of underwater or floating strUctures ~hich have to be effectively the same density as water for many survival, military and engineering applications. For example the structures can be used in fish farms or as floating booms for enclosing oil spills or in providing inflatable anchors, lightweight diving-bells. Indeed there may be provided self-inflating ta~s ~hich, in the presence of water, provide a rigid enclosing structure for liquids, e.g~ crude oil or organic solvents, which do not penetrate the water in the tank. Alternatively if it is desired to house an aqueous liquid in the tank, the tank needs to be provided with a water impermeable lining.
2~5595 Furthermore the present invention provides a met~od of purifying sea-water. In this embodiment a plurality ol envelopes according to the present invention m~y be contacted with sea-water and they will thus absorb w~ter from the sea. With some hydrogels some concentration of the water occurs by the selective absorption process. The envelopes thereby swo~len are drained of non-absorbed water and contained in a system such thatS under exposure to sunlight, they will be heated, e.g. by the sun~
causing absorbed water to be desorbed by the syneresis or evaporation from the hydrogel. For most efficient heating of the hydrogel the envelopes are preferably provided with a black body covering. The desorbed water from the hydrogel, which will be pure water, is then condensed e.g. for drinking. Suitably the water is condensed in a tank below t~le water level and therefore cooled by the body of water. This process provides an upside d~wn distillation in which the liquid sea-water being distilled is held in an upper immobile gelled form (having a large surface area corresponding to that of the surface of the swollen hydrogel particles) with the condenser underneath. This allcws simple advantage to be taken of the natural arrangement of the hot sun above and the cooling waters of the sea bel~. Additionally, to provide movement of the air over the devices and to enhance mass transfer of the water from the evaporator to the condenser, a fan to provide a flow of air over the devices may be provided. This apparatus provides an ef~icient process for producing potable or processed water from salt solution and has a very low energy consumption. It is suitable for small scale emergency water generation (e.g. for use in lifeboats) or for large scale desalination plants.
-12- 122~595 Any suitable hydrogel may be used in the envelope according to the present i~vention. ~he hydrogel used will generally be one which on swelling absorbs more than 40% of its dry weight of water with-out dissolution. The degree of swelling however ispreferably between 150% and 1000~o by weight though swellings of higher or lower degree are obtainable and usable. The hydrogel used is suitably one which exhibits syneresis, i.e. one which has the property of undergoing a substantially greater level of swelling in an aqueous medium at 0Cthan at a 100C. Accordingly water absorbed at lower temperatures will be spontaneously desorbed at the temperature of the hydrogel increased.
The hydrogels can be of natural or synthetic organic or inorganic material. mey are normally made of water soluble backbone materials which are rendered insoluble by the introduction of covalent crosslinks e.g. addition polymers of hydroxy alkyl(meth)acrylates, methyl vinyl ether, (meth)-acrylamide, N-vinyl pyrrolidone, (meth)acrylic acid and its salts, N-vinyl and C-vinyl pyridines and salts thereof with poly(meth)acrylates such as glycol dimethacrylate. There may also be used crosslinked natural polymers such as collagen or starch and cellulose derivatives and crosslinked synthetic polymers such as polyvinyl alcohol may be used.
Preferably there is used as hydrogel a crosslinked poly(ethylene glycol or e~hylene oxide).
Suitable crosslinked materials can be prepared by reacting poly(e~hylene oxide) or poly(ethylene glycol) with a polyol (e.g. 1,2,6-hexantriol) and a polyisocyanate (e.g. diphenylmeth~n4 4,4t_ diisocyanate~. Further there may be used insoluble _~ --13--~22~i595 domains (block copolymers of e.g. polyethylene oxide with water-insoluble urethane blocks) or m~terials rendered insoluble by entanglement crosslinking (hi~h molecular weight poly~ethylene oxides)) wi ~l divinylbenzene or by crystaIlinity ~cellulosic ~aterials).
The hydrogel used according to the present invention is in particulate form. Generally the hydrogel will be in granular, powder, strip, fibre or foamed form. me particles of the hydrogel must of course be large enough to be retained within the porous or permeable envelope even when they are in their dried, unswollen condition. Thus ~e average dry particle size will g~nerally be at least 1%
larger, and preferably at least twice (more preferably at least 10%) the size of the pores in the surrounding envelope. me particulate hydrogels for use in the present invention may co-~veniently be prepared by contacting the hydroge1 with water and subjecting the swollen hydrogel to shear stress such that it is comminuted to particles as described in British Patent Specification No: 2100269A.
It can be advantageous for the hydrogel particles according to the present invention to be in expanded form. Thus for example in the case of polyethylene oxide particles water present may react with added diisocyanate to liberate carbon dioxide gas to produce an expanded polymer. This can be advantageous firstly because the polye~ylene oxide in this way does not require a preliminary drying operation and, in addi~io~ the resulting expanded polymer may be more readily swollen and comminuted.
When the envelope according to the present - invention also contains pharmaceutically, veterinarily or biologically active ingredient in -14- ~22~595 .~stained release form, there may be mixed with the hydrogel particles particles containing the acbive ingredient in a sustained release f~rm for example as described in U.S. Patent Specifica~ions 4150108 and 4221779. Many formulations for the sustained release of active ingredients in this way are known.
Alternatively the active ingredient may be present, in sustained release form, in the hydrogel particles themselves. Suitable such compositions are ~lO described for example in British Patent Specifications Nos: 2047093A, Zo47094A and 2108517A.
me envelope according to the present invention is sized such that the volume of the quantity of hydrogel contained in it, when fully swollen (including any spaces inside or bet~een hydrogel particles) at 20C, amounts to at least 66% o~ the maximum non-stretched internal volume of the envelope. me ratio of envelope size to external volume of fully swollen hydrogel contained therein may vary according to the proposed use of the envelope. ~hus when the rigidity of the swollen envelope is important the non-stretched internal volume of the envelope will gener~lly be at least approximately equal to the external volume of the swollen hydrogel. mus the envelope material will be taut around the swollen hydrogel. In some applications, where mechanically very rigid structures are required, the maximum external volume of the ~u11y swollen hydrogel will be greater than 100% of the maximum ~o non-stretched internal volume of the envelope. Of course in this case the envelope must be made of material having sufficient strength to withstand the forces of compressed swollen hydrogel within.
In applications where rigidity is less important the volume of the swollen hydrogel may be less than -15- 1~59S
100% of the maximum non-stretched internal volume of the envelopeO Generally speaking the volume of the quantity of hydrogel, when fhlly swollen at 20C, amounts to at least 90 to 110%, most preferably a~
least 95 to 105%, of the maximum non-stretched internal volume of the envelope.
m e envelope is o~ porous or permeable material to all~ the water or water vapovr to reach the hydrog~l within. Further the envelope material must be flexible so that the ~nvelope is limp and flexible when the hydrogel is unswollen and of limited extensibility to obtain the required rigid structure when the hydrogel is swollen within the envelope. The actual material of the co~position of the envelope will depend upon the use to which it is to be put and the properties e.g. as regards strength reauired.
If a high degree of strength is no~ required then tne envelope may simply be of a textile mat such as paper or felt. For stronger structures knits, weaves and braids may typically be used. These may utilise natural or synthetic fibres of organic or inorganic materials, e.g. biodegradable natural proteins, fibril1ated polypropylene, polyester continuous filament, metal wire, fibreglass and carbon fibre.
Alternatively a continuous flexible sheet of plastics material or rubber, into which micro- or macropores have been introduced, may be used. The envelope will of course be closed to prevent escape of the hydrogel. mis closing may simply be by stitching, glueing or by heat sealing for example.
me shape of the envelope according to the present invention will vary according to the intended use. As mentioned above for the absorption of e.g. water vapour or condensation the envelope may suitably be in the form of a strip which, ~n 122~595 hydration of the hydrogel, swells up to form a cylinder. Also in the case of articles of personal hygiene and indeed for three dimensional structures which are self-erecting the shape of the envelope will very much be determined by the particular end use. When the envelope is one for introduction into a cavity or container having a narrow entrance and exit,-a most convenient shape is that of a toroid.
m us the envelope according to the invention may be formed from a tube, e.g. tubular braid, the hydrogel particles inserted and then the two ends brought together to form a toroid, loop or ring shaped. The limp flexible structure ~hen the hydrogel is substantially unswollen can readily be e.g. rolled up for introduction through the narrow entrance of the cavity or container. Once inside hcwever the envelope absorbs water and the volume fiIling structures thereby obtained are even less likely to be able to get out through the narrow entrances or exits- --If it is desired that the envelope and hydrogel material be discharged from the stomach after the e.g. veterinarily or pharmaceutically active ingredient has been released, the envelope may be of a- slowly dissolving material. In this way the hydrogel particles will be released after dissolution o~ the envelope and will thus be passed out from the stomach. Su~h bio-absorbable materials are weIl known in the food, pharmaceutical and surgical fields, e.g. collagen, various cellulosic derivatives and poly(lactic) or poly(glycolic) acids.
The invention is further iIlustrated, by way of Example, with reference to the ~ollowing Exa~ples and drawings - 16a -~Z2~i~;i95 Figure la illustrates a fabric tube of flat width and length;
Figure lb illustrates a cylindrical package formed from the tube of Figure la;
Figure lc is a cross-sectional view through the cylindrical package of Figure lb;
Figure 2a is a diagrammatic illustration of the unswollen device according to another embodiment;
Figure 2b diagrammatically illustrates the swollen device according to the example in Figure 2a; and Figures 3a and 3b shows an unswollen and swollen example respectively of a further example of the invention.
- 17 _ ~2 ~ ~T~9 5 EY~P~E 1 A polye-thyle~le oxide ihydrogel was prepared by the method des^ribed ln Exclmple 1 of Bri-tish Patel~v Specl~ication No. 2 047 03~h by reac-ting 50 g polye-thylene oxicle (Mn - r~350) with O~S8'~ ~ 1,2~6-hexanetriol and ~795 g bi~-(4-isoccyana'ocyclohe~y~l) methane (H~lene W ex du Pont) cor-respondirg to a molclr ratio o~ 1:0.75:2.125 respectively.
The fully swo~len hydrogel was then commiruted in a domes-tic liquidiser (~en~ood "Chef') for five minutes at a s'near rate of 1350~ rpm arld a volume ratio of 1:1 o f swollen pol-~ner to wa-ter. The conditions were selected to produce the ma~imum yield of particles of the requisi-te size for use in the f`abric con-tainer used in this ex~n-~le~
The particles were then fil-tered of~, washed thorovghly with boiling wa-ter,l and then dried by a through current of air.
One end of a :Eabrie tube was sti-tched closed with pol~ester thread. The fabric tu'be was a 77 cm.
leng-th circularly knitted tube, 2.5 cm ;~`lat wid-th, made on a 10 gauge flatbed machine ~rom 2 ellds o~
tex-tured pol~ester yarll (2~167 TeY~) thrc-aclecl tl~:rou~'n 15 needles fron^'t and back. 40 g dry hydrogel particles (840-1760 microns) ~ere in-troduced in-to -the fabric -tube and the open end o-f the -tubt? ~as sti-tehed elosed. At -this level of packing thc? ~;ub~
was of generally cireular cross sec-tion bi'-t co~ 'e wourlcl rolmd a 7.5 cm. dialne`ter ~Ol'mer Wit.~ t.-t,le resistanee.
~0 When -the device so ~ormed was co~l-l;actcd with water~ 140 ml. water -~ere absorhed b~r `t he hyd~ogt?lc The outside of the swollen device was "clr~T" -t:o the touch and tlle device had swollQn to a îirm cylindrical l~ael~a~ce with resistallce to b?~ldil~g~
~5 T}~e ~ n ~ ic~ lci`t ~c~ (`Zl~y ~ `r whereby the swollen shape was lost Then the device was re-used for absorption of water. The cycle of abscrption of water followed b~ air drying was carried out repeatedly without detectable alteration of the water uptake. Drying of the swollen device was on occasion speeded up by hanging it in a current of warm air and at other times, to reduce the drying time still further, by immersion in boiling water prior to drying.
Figure 1 accompanying the present specification iilustrates diagrammatically the device according to Example 1. Thus Figure 1A illustrates a fabric tube o~ flat width a and length b which on having hydrogel inserted inside, the ends closed and contacted with water swells to form a firm cylindrical package as shown in Figure 1B. Figure 1C is a cross-section through the cylindrical package of Figure 1B showing the fabric tube material 1 and the swollen hydrogel particles 2 inside.
A device was made similar in all respects to that described in Example 1 except that the particulate charge was prepared from a polyethylene oxide h,ydrogel obtained by the reaction o~ 60 g polyethylene oxide (rn -- 6427) with 2.75 g of a commercial di-isocyanato-diphenyl methane (Suprasec DND ex I.C.I.) containing some higher functionality isocyanates. These proportions correspond to a 10% excess of the di-isocyanate from a 1:1 mular ratio.
The water uptake of the hydrogel particles in the device so formed was of the same order as those o~
Example 1 and the swelling and drying behaviour were also similar.
EXA~IE 3 Small amounts o~ water present in polyethylene oxide will also react with added di-isocy~lates - 19 - 122~;i59S
libera-ting carbon dioxide gas to produce an expanded polymer. This can be advantageous in the production of absorbent particles in that the polyethylene oxide does no-t require a preliminary drying operation and the resulting expanded polymer is more readily swollen and comminuted.
100g polyethylene oxide (Mn = 6427) with a water content of 0.4% were reacted with 7.7 g di-isocyanato-diphenyl methane. The &mount of di-isocyanato-diphenyl me-thane was sufficient to react with the water and leave an excess of 10% above a 1:1 molar ra-tio.
The resulting expanded polymer was comminuted as in Example 1, except that the swollen polymer~
water mixture was subjected to shearing for 30 seconds instead of 5 minutes.
Using the particles thus obtained and a polyester braid tube, 2.0 cm. flat width, ~ormed on a 48 spindle machine using 5/115 Tex yarn, the ends of which were closed by heat sealing, there was made a device as in Example 1. The water uptake of the device was 180 ml. which was unaltered by repeated drying and re-absorption of water.
Hydrogel particles were obtained ~rom a cross-linked polymer, prepared by reacting polyethylene oxide (Mn = 7450)~ 1,2,6-hexane ~riol and acrolein~
tetramer as described in Example 6 o~ British Patent Specification No. 2 100 269A. Using a knitted nylon tube, the ends o~ which were closed by stitching with nylon thread, there was obtained a device similar to that described in Example 1, The absorptiQn and drying characteristics of the de~rice obtained were found to be similar to those o~ the device o~
Example 1, EXAMPLE 5 12255~5 A device was made by the method of Example 1 except that the particulate hydrogel charge was prepared by reacting polyethylene oxide (Mn = 4360), 1,2,6-hexane triol and b -(4-isocyanatocyclohexyl) methane in a 1:0.75:1.5 molar ratio.
The device absorbed 280 ml. water without feeling wet to the touch and a drying-water absorption cycle was repeated frequently without apparent change in effectiveness.
A circular tube of flat width 2 cm was knitted on a 10 gauge flat bed machine having ten needles front and back threaded with 3 ends of pale blue coloured polyester yarn *
(Dacron ex du Pont) of 1/150 denier count.
18 g of polyethylene oxide hydrogel particles obtained as described in Example 1 were inserted into 60 cm. length of the tube, the ends of which were overlapped by 2cm and stitched together with a polyester (Dacron) yarn to form a ring (like a headband).
When this device was contacted with water 60 ml. water were absorbed into the device. The swollen device thus formed was in the form of an inflated toroid which felt cool but not moist to the skin. This tubular ring was air dried and, after drying, it absorbed 50 ml. of a 3% (weight by volume) salt solution. The ring was then immersed in hot water, squeezed free of excess water and dried in warm air. Repetition of this operation (i.e. salt water absorption to drying) did not impair the absorption capacity of the device.
The device of this example is illustrated in Figure 2 of the accompanying drawings wherein Figure 2A shows diagrammatically the form of the * Trademark - 20 -12~2~T;~9~T
- 21 _ unswollen device whereas Figure 2B shows diagrammatic-ally the form of the swollen device of this ex~nple.
In both Figure 2A and Figure 2B 3 denotes the stitching of the ring together.
A ring device was prepared in the manner of Example 6 with the following modifications; the circular tube used was knitted using two ends of dark blue coloured crimped nylon yarn threaded through the knitting machine needles. The length of the tube used was 56 cm. and the ring was completed by stitching together with nylon thread a 1 cm. over-lap of one end of the tube to one end of a 4 cm.
length of 2 cm. wide elasticated strip, ~he other end of the tube was joined to the other end of the elasticated strip. Thus in the ring of this example there was a 2 cm. long extensible insert.
The results of absorption of water and of salt solution and of drying in this example did not differ from those of the ring described in Example 6.
EY~PLE 8 40 g of particulate polyethylene oxide/di-isoqanato-diphenyl methane hydrogel as described in Example 3 were introduced into a polyester braid tube, length 38 cm., also as described in Example 3.
The two ends of the charged tube were placed together to form a 1.5 cm. overlap and fused under controlled temperature and pressure conditions to form a ring device.
When the device was placed in water, it swelled into a doughnut-shape having an outer diameter of-`
14 cm. and with the dia~,eter of the swollen braid tube in the ring being 2.5 cm.
A tube of 3.5 cm. flat width was knitted on a circular weft knittin~ machine (No. 3 `'Lilliput"
~22~i59`~
machine) using 2 ends o~ textured polyester yarn (2/167 Tex) and 6~ needlesc A lengtl1 o~ 45 cm.
of -this -tube was ~illed with 45 g o* hydrogel particles prepared as described in Example 3. ~n annular device was made by stitching together ~ 'h cotton threads the two ends overlappirlg each o-ther by 2 cm.
When the device was ful]y swollen there was formed a ring having an outer diameter of 16 cm.
10 The diameter of the s~ollen tube forming the ring was then 3.5 cm.
EXAMPLE 'lO
A tube was knitted as in Example 9 using a single end OI the polyester yarn and 58 needles 15 producing a 2~5 cm. ~lat width tube. To 22 cm.
of this tube were added 16.5 g of hydrogel particles prepared as described in Example 1 and a 3 cm.
length of 0.7 cm. diameter s-teel rod weighing approxima-tely 20 g. With a 1 cm, overlap o* the e-nQs~
20 the ends of the tube were stitched toget'her using a polyester braid fishing line to form a ring device.
On immersion in water, -the device was swollen into a doughnut-shape.
The embodiment o~ this example is illustrated 25 in E'igure 3 of the accompanying drawings wherein Figure ~A shows the unswollen, dry device and Figure 3B shows the device after swelling in wa-ter. In Figure 3the steel rod is sho~ as ~-~ and the stitching of -the ring device as 5. The overall 30 dian~eter c o~ the ring is 7 cm. ~ld the diameter o~
the swollen ~-aid d is 2~2 cm~ in ~igure 3B
The presence of the steel rod in the device o*
this example can be used to make tihe position o~ the device in for ex~mple ~n anima'~'s stomach more l~eadil~r 35 detected si~lce the position o~ the me-tal c~l b~ detected *rom the ou-~side o~` the anill1al.
~2~ 5 EX~MPL~ 11 -The dry device o.~ ~xample 10 shown in ~igure 3A
was inser-ted into a -tube of cellulose fi]m -to provide a smooth outer surface.
EXA~LE 12 ___ The dry de~Tice of Example 10 shown in ~igure 3A
was inserted into a sausage sl~in -to provide a s~ooth outer surface.
A tube was knitted as-in Example 9 but to produce a 2.5 cm. flat width. 22 cm. of thi.s tube was charged with 20 g of hydrogel particles prepared by the method described in Example 1 and with 10 discs incorporating 20C/o pyrimethamine in di.hydropyran polymer prepared by the method described in Example 1 of UOS. Patent No. 4,221 9 779. The overlapped ends -of the -tubewere stitched together to form a ring device.
The ring devi.ce was swollen in water to the dimensions of the ring o~ Example 10 sho~ in Figure 3B of the accompanying d.rawings.
It is -repor-ted by Judge et al (Sustainecl release implants in the chemo-therapy of experimental rodenc malaria II, Annals of Tropical Medicine and Parasitology, Vol. 75, No. 5, 511-519 (1981)) that one disc as described above implanted subcu-re~eovsly protected mice agains-t challenge with Plasmod.i.u~
berghei (N strain) for more than 20 weeks.
E~.X.~PLE 1 l~
3 A polyester braid -tube as described in Ex~1ple 3 and of length 16~o cm. was hea-t sealed a-c one end.
13 g of hydrogel particies prepared as described in Example 2 were introduced -through the open end of the tube whi.h was then closed by heat sealing.
~en contac-ted wi-th wa-ter, the tube swelled to fOJ'II. a rigid cylindèr. The rl~easurements o~ the de~ice were GS follows~
12~55'35 Dry tube (flexible)Swollen tube (rigid) -Length 11.5 cm. 10.5 cm.
Width 2.4 cm 2.5 cm.
The volume of the gel in the dry tube was 33.5 ml while the internal volume of the swollen tube was 49.0 ml.
A knitted tubed as described in Example 1 of length 24 cm. was heat sealed at one end. 20 g of hydrogel particles prepared as described in Example 2 were introduced through the open end of the tube which was then stitched closed with polyester yarn.
On contacting with water the tube of the device swelled up to a straight cylindrical shape. The cylinder had some resistance to bending and returned to a straight cylindrical shape on removal of the bending forces.
The measurements of the device of this example were as follows:
Dry tube Swollen tube Length22.0 cm. 20.0 cm.
Width2.6 cm. 2.7 cm.
The volume of the gel in the dry tube was 43.0 ml. while the internal volume of the swollen tube was 114.0 ml.
A bag made from an 8 gauge single weft knitted fabric using 3 ends of 2/167 Tex polyester filament yarn and in the shape of a short cylinder 16 cm. in diameter and 7 cm. high was charged with 150 g of coarse (greater than 2000 microns) hydrogel particles prepared by the method described in Example 5.
~225595 The bag absorbed 1 litre of 3% (weight by volume) salt solution before it was near its limit of absorption.
The bag thereby swollen did not feel wet to the skin.
Immersion of the swollen bag in boiling water to remove the salt solution, followed by drying in hot air did not change the water absorption of the hydrogel.
- 24a -~22559~i There are introduced into a bag made from knitted fabric as described in Example 16 in the shape of a square cushion, 45 cm. side length, 8 cm. depth, 1.5 kg. of the coarse hydrogel particles used in Example 16. A cushion thereby obtained readily absorbed 3 litres of the salt solution without feeling wet to the touch.
0.85 mole freshly distilled methyl methacrylate was mixed with 0.14 mole hexaethoxylated hydroxy-ethylmethycrylate and 0.01 mole trimethylol propane trimethacryla-te. The mixture was warmed to 65C until reation was in.itiated whereafter the reaction was allowed to continue without further heating for 2 hou.rs to give a solid gel~ This gel was broken down into particles, packed very tightly into a tubular container.
When in contact with water the gel swelled to twice its original size.
Because the envelopes according to the present invention are limp and flexible in the subs-tantially dry, non-swollen state while being inflated and substantially rigid in the fully swollen state, they can be introduced into and then be retained in a cavity or container having a narrow entrance and exit. Thus the envelope can be rolled up if necessary to introduce it into the cavity or containe-r and, as long as the cavity or container has sufficient water therein, inside the hydrogel will swell causing the envelope to inflate to a rigid structure so that it is too lar~e to leave via either the -narrow entrance or the narrow exit. This is of particular interest in the veterinary and pharmaceutical fields.
Thus the envelopes according -to the presen-t invention may be used in the veterinary and pharmaceu3tical fields; particularly for the administration of sustained release compositions _ 8 - 1225595 to animals and human beings. It is of course well known to administer veterinarily, pharmaceutically or biologically active ingredients which are released within the animal or human being over an extended period of time following administration. Gne of the problems associated with such compositions is the ensuring that tlley are retained within the stomach for a sufficient length of time. Various compiicated devices have been proposed to ensure adequate retention in the stomach. Further, while this may not be a problem with animals for slaughter, especially with human patients, it is desirable that the device should, after all the active ingredient has been used up, be itself discharged from the stomach.
Suitable veterinarily active ingredients include antiinfective agents e.g. bacteriorcides, such as anti-biotics and viruscides: anti-parasitic agents e.q.
nematicides: oral vacines: and growth-promoting agents e.g. anabolics, trace elements and vitamins. Trace element preparations may include one or more of magnesium, iron, iodine, copper, cobalt, manganese, zinc and selenium, es~ecially copper, cobalt, selenium or iodine.
Accordingly the present invention also provides ~5 an envelope having flexible, water-permeable or porous walls ~nd a given r.~ximum non-stretched internal volur.le and contai-ning a quantity of particulate water-insoluble hydrogel an~ a pharm~ceutically, veterinarily or biologically active ingredient in sustained release form in the closed e~velope wherein the v~lume of the quantity of hydrogel when fully swollen at 20C amoun~s to at least 66% of the given maximum non-stretched internal volume but is insufficient when ~ully swollen at 20C to rupture the envelope, -9 12~i59~
This envelope, in the non-swollen state, can simply be rolled up if necessary and swallowed by the patient or ~orced down the throat of an a~imal being treated by a conventional means such as a bolus gun. In the stomach water traversing the water-permeable or porous ~lalls of the envelope will be absorbed by the hydrogel from the stomach juices and accordingly the envelope will swell up in the s~omach to its inflated form. Accordingly there it will be retained within the stomach during the sustained release of the active ingredient. mus the present invention offers a very simple solution to the problem of retention of sust~ined release compositions in the stomach.
15 ~~~ It may be convenient in some applications, ~or ease of administration, to have the envelope contained in a second outer package which provides some rigidity to the unswollen floppy form of the device. This outer package can ease administration by making it more easy 20 to swallow. The outer package subsequently ruptures by degradation of its adhesive, stitching or of its material or merely under the pressure exerted by the envelope when it swells inside. For example a paper tube, a collagen skin or a plastics film with protein adhesive 25 all provide suitable exteriors to enable the devices to be swallowed or placed in position more easily Envelopes according to the present illvention can also be used as slimming aids. Thus the envelopes, ~Yhich in t~is case need not con~ain any 30 pharmaceutically active ingredient, can be s~lall~wed by someone wanting to slim. T~R envelope will swell and be retained in the human stomach to provide a feeling of fuIlness and thus reduce appetite.
12~5595 A yet further application of the present invention is in the providing of self-erecting three dimensional structures. These structures may be of any desired shape. The structures can comprise a single envelope according to the invention or can comprise a plurality of compartments joined together, each compartment having a given maximum non-stretched internal volume and containing a quantity of particulate water-insoluble hydrogel wherein the volume of thQ auantity of hydrogel when fully swollen at 20C amounts to at least 66SS, preferably at least 100%, of the given maximuril non-stretched internal volume but is insufficient when fully swollen at 20~C to rupture the compartment.
These structures will be self-erecting when wetted, e.g. in the rain or by immersing or spraying with water. In this way large rigid structures may be obtained. Of course the structures according to the present invention have to be maintained in wet conditions if they are to stay sufficiently rigid.
Thus they will generally be used for the rapid erection of underwater or floating strUctures ~hich have to be effectively the same density as water for many survival, military and engineering applications. For example the structures can be used in fish farms or as floating booms for enclosing oil spills or in providing inflatable anchors, lightweight diving-bells. Indeed there may be provided self-inflating ta~s ~hich, in the presence of water, provide a rigid enclosing structure for liquids, e.g~ crude oil or organic solvents, which do not penetrate the water in the tank. Alternatively if it is desired to house an aqueous liquid in the tank, the tank needs to be provided with a water impermeable lining.
2~5595 Furthermore the present invention provides a met~od of purifying sea-water. In this embodiment a plurality ol envelopes according to the present invention m~y be contacted with sea-water and they will thus absorb w~ter from the sea. With some hydrogels some concentration of the water occurs by the selective absorption process. The envelopes thereby swo~len are drained of non-absorbed water and contained in a system such thatS under exposure to sunlight, they will be heated, e.g. by the sun~
causing absorbed water to be desorbed by the syneresis or evaporation from the hydrogel. For most efficient heating of the hydrogel the envelopes are preferably provided with a black body covering. The desorbed water from the hydrogel, which will be pure water, is then condensed e.g. for drinking. Suitably the water is condensed in a tank below t~le water level and therefore cooled by the body of water. This process provides an upside d~wn distillation in which the liquid sea-water being distilled is held in an upper immobile gelled form (having a large surface area corresponding to that of the surface of the swollen hydrogel particles) with the condenser underneath. This allcws simple advantage to be taken of the natural arrangement of the hot sun above and the cooling waters of the sea bel~. Additionally, to provide movement of the air over the devices and to enhance mass transfer of the water from the evaporator to the condenser, a fan to provide a flow of air over the devices may be provided. This apparatus provides an ef~icient process for producing potable or processed water from salt solution and has a very low energy consumption. It is suitable for small scale emergency water generation (e.g. for use in lifeboats) or for large scale desalination plants.
-12- 122~595 Any suitable hydrogel may be used in the envelope according to the present i~vention. ~he hydrogel used will generally be one which on swelling absorbs more than 40% of its dry weight of water with-out dissolution. The degree of swelling however ispreferably between 150% and 1000~o by weight though swellings of higher or lower degree are obtainable and usable. The hydrogel used is suitably one which exhibits syneresis, i.e. one which has the property of undergoing a substantially greater level of swelling in an aqueous medium at 0Cthan at a 100C. Accordingly water absorbed at lower temperatures will be spontaneously desorbed at the temperature of the hydrogel increased.
The hydrogels can be of natural or synthetic organic or inorganic material. mey are normally made of water soluble backbone materials which are rendered insoluble by the introduction of covalent crosslinks e.g. addition polymers of hydroxy alkyl(meth)acrylates, methyl vinyl ether, (meth)-acrylamide, N-vinyl pyrrolidone, (meth)acrylic acid and its salts, N-vinyl and C-vinyl pyridines and salts thereof with poly(meth)acrylates such as glycol dimethacrylate. There may also be used crosslinked natural polymers such as collagen or starch and cellulose derivatives and crosslinked synthetic polymers such as polyvinyl alcohol may be used.
Preferably there is used as hydrogel a crosslinked poly(ethylene glycol or e~hylene oxide).
Suitable crosslinked materials can be prepared by reacting poly(e~hylene oxide) or poly(ethylene glycol) with a polyol (e.g. 1,2,6-hexantriol) and a polyisocyanate (e.g. diphenylmeth~n4 4,4t_ diisocyanate~. Further there may be used insoluble _~ --13--~22~i595 domains (block copolymers of e.g. polyethylene oxide with water-insoluble urethane blocks) or m~terials rendered insoluble by entanglement crosslinking (hi~h molecular weight poly~ethylene oxides)) wi ~l divinylbenzene or by crystaIlinity ~cellulosic ~aterials).
The hydrogel used according to the present invention is in particulate form. Generally the hydrogel will be in granular, powder, strip, fibre or foamed form. me particles of the hydrogel must of course be large enough to be retained within the porous or permeable envelope even when they are in their dried, unswollen condition. Thus ~e average dry particle size will g~nerally be at least 1%
larger, and preferably at least twice (more preferably at least 10%) the size of the pores in the surrounding envelope. me particulate hydrogels for use in the present invention may co-~veniently be prepared by contacting the hydroge1 with water and subjecting the swollen hydrogel to shear stress such that it is comminuted to particles as described in British Patent Specification No: 2100269A.
It can be advantageous for the hydrogel particles according to the present invention to be in expanded form. Thus for example in the case of polyethylene oxide particles water present may react with added diisocyanate to liberate carbon dioxide gas to produce an expanded polymer. This can be advantageous firstly because the polye~ylene oxide in this way does not require a preliminary drying operation and, in addi~io~ the resulting expanded polymer may be more readily swollen and comminuted.
When the envelope according to the present - invention also contains pharmaceutically, veterinarily or biologically active ingredient in -14- ~22~595 .~stained release form, there may be mixed with the hydrogel particles particles containing the acbive ingredient in a sustained release f~rm for example as described in U.S. Patent Specifica~ions 4150108 and 4221779. Many formulations for the sustained release of active ingredients in this way are known.
Alternatively the active ingredient may be present, in sustained release form, in the hydrogel particles themselves. Suitable such compositions are ~lO described for example in British Patent Specifications Nos: 2047093A, Zo47094A and 2108517A.
me envelope according to the present invention is sized such that the volume of the quantity of hydrogel contained in it, when fully swollen (including any spaces inside or bet~een hydrogel particles) at 20C, amounts to at least 66% o~ the maximum non-stretched internal volume of the envelope. me ratio of envelope size to external volume of fully swollen hydrogel contained therein may vary according to the proposed use of the envelope. ~hus when the rigidity of the swollen envelope is important the non-stretched internal volume of the envelope will gener~lly be at least approximately equal to the external volume of the swollen hydrogel. mus the envelope material will be taut around the swollen hydrogel. In some applications, where mechanically very rigid structures are required, the maximum external volume of the ~u11y swollen hydrogel will be greater than 100% of the maximum ~o non-stretched internal volume of the envelope. Of course in this case the envelope must be made of material having sufficient strength to withstand the forces of compressed swollen hydrogel within.
In applications where rigidity is less important the volume of the swollen hydrogel may be less than -15- 1~59S
100% of the maximum non-stretched internal volume of the envelopeO Generally speaking the volume of the quantity of hydrogel, when fhlly swollen at 20C, amounts to at least 90 to 110%, most preferably a~
least 95 to 105%, of the maximum non-stretched internal volume of the envelope.
m e envelope is o~ porous or permeable material to all~ the water or water vapovr to reach the hydrog~l within. Further the envelope material must be flexible so that the ~nvelope is limp and flexible when the hydrogel is unswollen and of limited extensibility to obtain the required rigid structure when the hydrogel is swollen within the envelope. The actual material of the co~position of the envelope will depend upon the use to which it is to be put and the properties e.g. as regards strength reauired.
If a high degree of strength is no~ required then tne envelope may simply be of a textile mat such as paper or felt. For stronger structures knits, weaves and braids may typically be used. These may utilise natural or synthetic fibres of organic or inorganic materials, e.g. biodegradable natural proteins, fibril1ated polypropylene, polyester continuous filament, metal wire, fibreglass and carbon fibre.
Alternatively a continuous flexible sheet of plastics material or rubber, into which micro- or macropores have been introduced, may be used. The envelope will of course be closed to prevent escape of the hydrogel. mis closing may simply be by stitching, glueing or by heat sealing for example.
me shape of the envelope according to the present invention will vary according to the intended use. As mentioned above for the absorption of e.g. water vapour or condensation the envelope may suitably be in the form of a strip which, ~n 122~595 hydration of the hydrogel, swells up to form a cylinder. Also in the case of articles of personal hygiene and indeed for three dimensional structures which are self-erecting the shape of the envelope will very much be determined by the particular end use. When the envelope is one for introduction into a cavity or container having a narrow entrance and exit,-a most convenient shape is that of a toroid.
m us the envelope according to the invention may be formed from a tube, e.g. tubular braid, the hydrogel particles inserted and then the two ends brought together to form a toroid, loop or ring shaped. The limp flexible structure ~hen the hydrogel is substantially unswollen can readily be e.g. rolled up for introduction through the narrow entrance of the cavity or container. Once inside hcwever the envelope absorbs water and the volume fiIling structures thereby obtained are even less likely to be able to get out through the narrow entrances or exits- --If it is desired that the envelope and hydrogel material be discharged from the stomach after the e.g. veterinarily or pharmaceutically active ingredient has been released, the envelope may be of a- slowly dissolving material. In this way the hydrogel particles will be released after dissolution o~ the envelope and will thus be passed out from the stomach. Su~h bio-absorbable materials are weIl known in the food, pharmaceutical and surgical fields, e.g. collagen, various cellulosic derivatives and poly(lactic) or poly(glycolic) acids.
The invention is further iIlustrated, by way of Example, with reference to the ~ollowing Exa~ples and drawings - 16a -~Z2~i~;i95 Figure la illustrates a fabric tube of flat width and length;
Figure lb illustrates a cylindrical package formed from the tube of Figure la;
Figure lc is a cross-sectional view through the cylindrical package of Figure lb;
Figure 2a is a diagrammatic illustration of the unswollen device according to another embodiment;
Figure 2b diagrammatically illustrates the swollen device according to the example in Figure 2a; and Figures 3a and 3b shows an unswollen and swollen example respectively of a further example of the invention.
- 17 _ ~2 ~ ~T~9 5 EY~P~E 1 A polye-thyle~le oxide ihydrogel was prepared by the method des^ribed ln Exclmple 1 of Bri-tish Patel~v Specl~ication No. 2 047 03~h by reac-ting 50 g polye-thylene oxicle (Mn - r~350) with O~S8'~ ~ 1,2~6-hexanetriol and ~795 g bi~-(4-isoccyana'ocyclohe~y~l) methane (H~lene W ex du Pont) cor-respondirg to a molclr ratio o~ 1:0.75:2.125 respectively.
The fully swo~len hydrogel was then commiruted in a domes-tic liquidiser (~en~ood "Chef') for five minutes at a s'near rate of 1350~ rpm arld a volume ratio of 1:1 o f swollen pol-~ner to wa-ter. The conditions were selected to produce the ma~imum yield of particles of the requisi-te size for use in the f`abric con-tainer used in this ex~n-~le~
The particles were then fil-tered of~, washed thorovghly with boiling wa-ter,l and then dried by a through current of air.
One end of a :Eabrie tube was sti-tched closed with pol~ester thread. The fabric tu'be was a 77 cm.
leng-th circularly knitted tube, 2.5 cm ;~`lat wid-th, made on a 10 gauge flatbed machine ~rom 2 ellds o~
tex-tured pol~ester yarll (2~167 TeY~) thrc-aclecl tl~:rou~'n 15 needles fron^'t and back. 40 g dry hydrogel particles (840-1760 microns) ~ere in-troduced in-to -the fabric -tube and the open end o-f the -tubt? ~as sti-tehed elosed. At -this level of packing thc? ~;ub~
was of generally cireular cross sec-tion bi'-t co~ 'e wourlcl rolmd a 7.5 cm. dialne`ter ~Ol'mer Wit.~ t.-t,le resistanee.
~0 When -the device so ~ormed was co~l-l;actcd with water~ 140 ml. water -~ere absorhed b~r `t he hyd~ogt?lc The outside of the swollen device was "clr~T" -t:o the touch and tlle device had swollQn to a îirm cylindrical l~ael~a~ce with resistallce to b?~ldil~g~
~5 T}~e ~ n ~ ic~ lci`t ~c~ (`Zl~y ~ `r whereby the swollen shape was lost Then the device was re-used for absorption of water. The cycle of abscrption of water followed b~ air drying was carried out repeatedly without detectable alteration of the water uptake. Drying of the swollen device was on occasion speeded up by hanging it in a current of warm air and at other times, to reduce the drying time still further, by immersion in boiling water prior to drying.
Figure 1 accompanying the present specification iilustrates diagrammatically the device according to Example 1. Thus Figure 1A illustrates a fabric tube o~ flat width a and length b which on having hydrogel inserted inside, the ends closed and contacted with water swells to form a firm cylindrical package as shown in Figure 1B. Figure 1C is a cross-section through the cylindrical package of Figure 1B showing the fabric tube material 1 and the swollen hydrogel particles 2 inside.
A device was made similar in all respects to that described in Example 1 except that the particulate charge was prepared from a polyethylene oxide h,ydrogel obtained by the reaction o~ 60 g polyethylene oxide (rn -- 6427) with 2.75 g of a commercial di-isocyanato-diphenyl methane (Suprasec DND ex I.C.I.) containing some higher functionality isocyanates. These proportions correspond to a 10% excess of the di-isocyanate from a 1:1 mular ratio.
The water uptake of the hydrogel particles in the device so formed was of the same order as those o~
Example 1 and the swelling and drying behaviour were also similar.
EXA~IE 3 Small amounts o~ water present in polyethylene oxide will also react with added di-isocy~lates - 19 - 122~;i59S
libera-ting carbon dioxide gas to produce an expanded polymer. This can be advantageous in the production of absorbent particles in that the polyethylene oxide does no-t require a preliminary drying operation and the resulting expanded polymer is more readily swollen and comminuted.
100g polyethylene oxide (Mn = 6427) with a water content of 0.4% were reacted with 7.7 g di-isocyanato-diphenyl methane. The &mount of di-isocyanato-diphenyl me-thane was sufficient to react with the water and leave an excess of 10% above a 1:1 molar ra-tio.
The resulting expanded polymer was comminuted as in Example 1, except that the swollen polymer~
water mixture was subjected to shearing for 30 seconds instead of 5 minutes.
Using the particles thus obtained and a polyester braid tube, 2.0 cm. flat width, ~ormed on a 48 spindle machine using 5/115 Tex yarn, the ends of which were closed by heat sealing, there was made a device as in Example 1. The water uptake of the device was 180 ml. which was unaltered by repeated drying and re-absorption of water.
Hydrogel particles were obtained ~rom a cross-linked polymer, prepared by reacting polyethylene oxide (Mn = 7450)~ 1,2,6-hexane ~riol and acrolein~
tetramer as described in Example 6 o~ British Patent Specification No. 2 100 269A. Using a knitted nylon tube, the ends o~ which were closed by stitching with nylon thread, there was obtained a device similar to that described in Example 1, The absorptiQn and drying characteristics of the de~rice obtained were found to be similar to those o~ the device o~
Example 1, EXAMPLE 5 12255~5 A device was made by the method of Example 1 except that the particulate hydrogel charge was prepared by reacting polyethylene oxide (Mn = 4360), 1,2,6-hexane triol and b -(4-isocyanatocyclohexyl) methane in a 1:0.75:1.5 molar ratio.
The device absorbed 280 ml. water without feeling wet to the touch and a drying-water absorption cycle was repeated frequently without apparent change in effectiveness.
A circular tube of flat width 2 cm was knitted on a 10 gauge flat bed machine having ten needles front and back threaded with 3 ends of pale blue coloured polyester yarn *
(Dacron ex du Pont) of 1/150 denier count.
18 g of polyethylene oxide hydrogel particles obtained as described in Example 1 were inserted into 60 cm. length of the tube, the ends of which were overlapped by 2cm and stitched together with a polyester (Dacron) yarn to form a ring (like a headband).
When this device was contacted with water 60 ml. water were absorbed into the device. The swollen device thus formed was in the form of an inflated toroid which felt cool but not moist to the skin. This tubular ring was air dried and, after drying, it absorbed 50 ml. of a 3% (weight by volume) salt solution. The ring was then immersed in hot water, squeezed free of excess water and dried in warm air. Repetition of this operation (i.e. salt water absorption to drying) did not impair the absorption capacity of the device.
The device of this example is illustrated in Figure 2 of the accompanying drawings wherein Figure 2A shows diagrammatically the form of the * Trademark - 20 -12~2~T;~9~T
- 21 _ unswollen device whereas Figure 2B shows diagrammatic-ally the form of the swollen device of this ex~nple.
In both Figure 2A and Figure 2B 3 denotes the stitching of the ring together.
A ring device was prepared in the manner of Example 6 with the following modifications; the circular tube used was knitted using two ends of dark blue coloured crimped nylon yarn threaded through the knitting machine needles. The length of the tube used was 56 cm. and the ring was completed by stitching together with nylon thread a 1 cm. over-lap of one end of the tube to one end of a 4 cm.
length of 2 cm. wide elasticated strip, ~he other end of the tube was joined to the other end of the elasticated strip. Thus in the ring of this example there was a 2 cm. long extensible insert.
The results of absorption of water and of salt solution and of drying in this example did not differ from those of the ring described in Example 6.
EY~PLE 8 40 g of particulate polyethylene oxide/di-isoqanato-diphenyl methane hydrogel as described in Example 3 were introduced into a polyester braid tube, length 38 cm., also as described in Example 3.
The two ends of the charged tube were placed together to form a 1.5 cm. overlap and fused under controlled temperature and pressure conditions to form a ring device.
When the device was placed in water, it swelled into a doughnut-shape having an outer diameter of-`
14 cm. and with the dia~,eter of the swollen braid tube in the ring being 2.5 cm.
A tube of 3.5 cm. flat width was knitted on a circular weft knittin~ machine (No. 3 `'Lilliput"
~22~i59`~
machine) using 2 ends o~ textured polyester yarn (2/167 Tex) and 6~ needlesc A lengtl1 o~ 45 cm.
of -this -tube was ~illed with 45 g o* hydrogel particles prepared as described in Example 3. ~n annular device was made by stitching together ~ 'h cotton threads the two ends overlappirlg each o-ther by 2 cm.
When the device was ful]y swollen there was formed a ring having an outer diameter of 16 cm.
10 The diameter of the s~ollen tube forming the ring was then 3.5 cm.
EXAMPLE 'lO
A tube was knitted as in Example 9 using a single end OI the polyester yarn and 58 needles 15 producing a 2~5 cm. ~lat width tube. To 22 cm.
of this tube were added 16.5 g of hydrogel particles prepared as described in Example 1 and a 3 cm.
length of 0.7 cm. diameter s-teel rod weighing approxima-tely 20 g. With a 1 cm, overlap o* the e-nQs~
20 the ends of the tube were stitched toget'her using a polyester braid fishing line to form a ring device.
On immersion in water, -the device was swollen into a doughnut-shape.
The embodiment o~ this example is illustrated 25 in E'igure 3 of the accompanying drawings wherein Figure ~A shows the unswollen, dry device and Figure 3B shows the device after swelling in wa-ter. In Figure 3the steel rod is sho~ as ~-~ and the stitching of -the ring device as 5. The overall 30 dian~eter c o~ the ring is 7 cm. ~ld the diameter o~
the swollen ~-aid d is 2~2 cm~ in ~igure 3B
The presence of the steel rod in the device o*
this example can be used to make tihe position o~ the device in for ex~mple ~n anima'~'s stomach more l~eadil~r 35 detected si~lce the position o~ the me-tal c~l b~ detected *rom the ou-~side o~` the anill1al.
~2~ 5 EX~MPL~ 11 -The dry device o.~ ~xample 10 shown in ~igure 3A
was inser-ted into a -tube of cellulose fi]m -to provide a smooth outer surface.
EXA~LE 12 ___ The dry de~Tice of Example 10 shown in ~igure 3A
was inserted into a sausage sl~in -to provide a s~ooth outer surface.
A tube was knitted as-in Example 9 but to produce a 2.5 cm. flat width. 22 cm. of thi.s tube was charged with 20 g of hydrogel particles prepared by the method described in Example 1 and with 10 discs incorporating 20C/o pyrimethamine in di.hydropyran polymer prepared by the method described in Example 1 of UOS. Patent No. 4,221 9 779. The overlapped ends -of the -tubewere stitched together to form a ring device.
The ring devi.ce was swollen in water to the dimensions of the ring o~ Example 10 sho~ in Figure 3B of the accompanying d.rawings.
It is -repor-ted by Judge et al (Sustainecl release implants in the chemo-therapy of experimental rodenc malaria II, Annals of Tropical Medicine and Parasitology, Vol. 75, No. 5, 511-519 (1981)) that one disc as described above implanted subcu-re~eovsly protected mice agains-t challenge with Plasmod.i.u~
berghei (N strain) for more than 20 weeks.
E~.X.~PLE 1 l~
3 A polyester braid -tube as described in Ex~1ple 3 and of length 16~o cm. was hea-t sealed a-c one end.
13 g of hydrogel particies prepared as described in Example 2 were introduced -through the open end of the tube whi.h was then closed by heat sealing.
~en contac-ted wi-th wa-ter, the tube swelled to fOJ'II. a rigid cylindèr. The rl~easurements o~ the de~ice were GS follows~
12~55'35 Dry tube (flexible)Swollen tube (rigid) -Length 11.5 cm. 10.5 cm.
Width 2.4 cm 2.5 cm.
The volume of the gel in the dry tube was 33.5 ml while the internal volume of the swollen tube was 49.0 ml.
A knitted tubed as described in Example 1 of length 24 cm. was heat sealed at one end. 20 g of hydrogel particles prepared as described in Example 2 were introduced through the open end of the tube which was then stitched closed with polyester yarn.
On contacting with water the tube of the device swelled up to a straight cylindrical shape. The cylinder had some resistance to bending and returned to a straight cylindrical shape on removal of the bending forces.
The measurements of the device of this example were as follows:
Dry tube Swollen tube Length22.0 cm. 20.0 cm.
Width2.6 cm. 2.7 cm.
The volume of the gel in the dry tube was 43.0 ml. while the internal volume of the swollen tube was 114.0 ml.
A bag made from an 8 gauge single weft knitted fabric using 3 ends of 2/167 Tex polyester filament yarn and in the shape of a short cylinder 16 cm. in diameter and 7 cm. high was charged with 150 g of coarse (greater than 2000 microns) hydrogel particles prepared by the method described in Example 5.
~225595 The bag absorbed 1 litre of 3% (weight by volume) salt solution before it was near its limit of absorption.
The bag thereby swollen did not feel wet to the skin.
Immersion of the swollen bag in boiling water to remove the salt solution, followed by drying in hot air did not change the water absorption of the hydrogel.
- 24a -~22559~i There are introduced into a bag made from knitted fabric as described in Example 16 in the shape of a square cushion, 45 cm. side length, 8 cm. depth, 1.5 kg. of the coarse hydrogel particles used in Example 16. A cushion thereby obtained readily absorbed 3 litres of the salt solution without feeling wet to the touch.
0.85 mole freshly distilled methyl methacrylate was mixed with 0.14 mole hexaethoxylated hydroxy-ethylmethycrylate and 0.01 mole trimethylol propane trimethacryla-te. The mixture was warmed to 65C until reation was in.itiated whereafter the reaction was allowed to continue without further heating for 2 hou.rs to give a solid gel~ This gel was broken down into particles, packed very tightly into a tubular container.
When in contact with water the gel swelled to twice its original size.
Claims (6)
1. An envelope having flexible water-permeable or porous walls and a given maximum non-stretched internal volume and containing a quantity of particulate water-insoluble hydrogel and a pharmaceutically, veterinarily or biologically active ingredient in sustained release form in the closed envelope wherein the volume of the quantity of hydrogel when fully swollen at 20°C amounts to at least 66% of the given maximum non-stretched internal volume but is insufficient when fully swollen at 20°C to rupture the envelope.
2. An envelope according to claim 1 wherein the quantity of hydrogel when fully swollen at 20°C amounts to at least 100% of the given maximum non-stretched internal volume.
3. An envelope according to claim 1 wherein the hydrogel is a crosslinked polyethylene glycol.
4. An envelope according to claim 1 which contains a mixture of hydrogel particles and particles of active ingredient in sustained release form.
5. An envelope according to claim 1 wherein the active ingredient in sustained release form is contained in the hydrogel particles.
6. An envelope according to claim 1 which is in the form of a toroid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8305797 | 1983-03-02 | ||
| GB838305797A GB8305797D0 (en) | 1983-03-02 | 1983-03-02 | Hydrogel-containing envelopes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1225595A true CA1225595A (en) | 1987-08-18 |
Family
ID=10538889
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000448619A Expired CA1225595A (en) | 1983-03-02 | 1984-03-01 | Hydrogel-containing envelopes |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5147646A (en) |
| EP (1) | EP0121331B1 (en) |
| JP (1) | JPS59196815A (en) |
| AU (1) | AU562797B2 (en) |
| CA (1) | CA1225595A (en) |
| DE (1) | DE3483276D1 (en) |
| DK (1) | DK162373C (en) |
| GB (2) | GB8305797D0 (en) |
| NZ (1) | NZ207362A (en) |
| ZA (1) | ZA841594B (en) |
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-
1983
- 1983-03-02 GB GB838305797A patent/GB8305797D0/en active Pending
-
1984
- 1984-02-29 DK DK148284A patent/DK162373C/en not_active IP Right Cessation
- 1984-03-01 GB GB08405405A patent/GB2144051B/en not_active Expired
- 1984-03-01 EP EP84301349A patent/EP0121331B1/en not_active Expired - Lifetime
- 1984-03-01 CA CA000448619A patent/CA1225595A/en not_active Expired
- 1984-03-01 DE DE8484301349T patent/DE3483276D1/en not_active Expired - Lifetime
- 1984-03-02 NZ NZ207362A patent/NZ207362A/en unknown
- 1984-03-02 ZA ZA841594A patent/ZA841594B/en unknown
- 1984-03-02 JP JP59041201A patent/JPS59196815A/en active Pending
- 1984-03-02 AU AU25224/84A patent/AU562797B2/en not_active Ceased
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1991
- 1991-09-16 US US07/759,623 patent/US5147646A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0121331A2 (en) | 1984-10-10 |
| AU562797B2 (en) | 1987-06-18 |
| DE3483276D1 (en) | 1990-10-31 |
| DK162373B (en) | 1991-10-21 |
| AU2522484A (en) | 1984-09-06 |
| GB2144051B (en) | 1986-10-15 |
| US5147646A (en) | 1992-09-15 |
| ZA841594B (en) | 1985-05-29 |
| EP0121331A3 (en) | 1986-08-13 |
| GB8405405D0 (en) | 1984-04-04 |
| DK162373C (en) | 1992-03-09 |
| DK148284D0 (en) | 1984-02-29 |
| GB8305797D0 (en) | 1983-04-07 |
| EP0121331B1 (en) | 1990-09-26 |
| JPS59196815A (en) | 1984-11-08 |
| NZ207362A (en) | 1987-05-29 |
| DK148284A (en) | 1984-09-03 |
| GB2144051A (en) | 1985-02-27 |
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