CA2039457A1 - Ringer's solution - Google Patents
Ringer's solutionInfo
- Publication number
- CA2039457A1 CA2039457A1 CA 2039457 CA2039457A CA2039457A1 CA 2039457 A1 CA2039457 A1 CA 2039457A1 CA 2039457 CA2039457 CA 2039457 CA 2039457 A CA2039457 A CA 2039457A CA 2039457 A1 CA2039457 A1 CA 2039457A1
- Authority
- CA
- Canada
- Prior art keywords
- solution
- ringer
- wounds
- treatment
- case
- 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.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
- A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
- A01N47/44—Guanidine; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
- A61L2300/206—Biguanides, e.g. chlorohexidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
Abstract
[File No. 74140-2]
A B S T R A C T
A lactate-free pure ring solution which, in addition, contains 0.1% of a dissolved concentrate which consists of a 20% aqueous polyhexamethylene biguanidine hydrochloride solution in which, per 100 ml, 1 g polyethylene glycol having a molecular weight of about 4000 is dissolved, used for local bacterial decontamination of wounds on a sterilized or saprophytic state and is thus used as a bactericidal medicine for treating wounds.
A B S T R A C T
A lactate-free pure ring solution which, in addition, contains 0.1% of a dissolved concentrate which consists of a 20% aqueous polyhexamethylene biguanidine hydrochloride solution in which, per 100 ml, 1 g polyethylene glycol having a molecular weight of about 4000 is dissolved, used for local bacterial decontamination of wounds on a sterilized or saprophytic state and is thus used as a bactericidal medicine for treating wounds.
Description
2~9 ~5~
IN T1113 P~\TENT OFFICE OE~ T}IE UNIT13D S l`i~ l'E~
--A RINGER'S SOLUTION--13ACKGI~OIJND OF TIIE INVENTION.
The invention relates to a lactate-rree pure R;nger's solut;on with additives which make it suitable for the decontnmination of woun(ls so that their c onclition is sterile or saprophytic and for maintaining such a condition during the entire healing process.
The invention is more part;cularly intcndecl to prov;de a Ringer's solution with such additives that it is equnlly suitable as a medicament with bactericidal properties applied in thel~apeutic meLhods for the local treatment of infected wounds, for the local prol hylatic treatnlent of wounds liable to become infected more particulm~ly du~ lg nn operation an~i for local decontamirlation Or wounds to free them of bacteria durillg the process o~ healing.
t5 A large number o~ wound treatment materials are known which however are not completely satisfactory or are unsuitable for application as medicaments owing to insufficient compatibility with the body tissues, their high protein error (i. e. to impairment of the bactericidal action in the presence of protein, as for instance wound e~udation and blood), their partly insufficient bactericidal action and their disadvantageous property of being resorbed by the body in greater or lesser quantities. A further point to be considered is that the tissue compatibility of such materials is frequently is not sul`ficient - owing to an e~cessive surface tension.
The administration of iodophors for the treatment o.f wounds involves the danger of resorption of iodine and thus the possibility of iodine-induced disorders. Furthermore iodophors have a significant protein error. With a iodophor dilution of 1:10 it is still possible, 203~
.he IaboI iIl;ory~ to I)ro(luce n good bactericidal action, whi(.dl llowever in the presence of 20% oï whole blood ;s more or less compIetely carIcelecI ouI. Owing lo the hazard of poterlti.tll~y fntal postopeI~ntive shock con(lit;iorIs the i~Itrnabdominal admin;strat;orl of iodoI)tloI~s h(ls been coml-IeteIy abandone(l, II~ ;ts action chlorhexidine is essentially solely bacteriostatic anà is no longer recommended for local wound treatrlIent;.
It is frequentIy objected that operation wounds are not able to be sufficierltIy protected against pathogenic organisms which are nlways able to perva(le the wound or which are present in the body ns ben;gn microorganisms in the body and nre only rendered pathogenic by the operation.
The infection haæard in the case of operations is therefore still nppreciable, Ihis hnving a connection with the incrensing resistance to antibiotics. A further point to be considered is ttlaI;
owing to the danger of serious side-effects woIlnd trentIllerlt mrlI eI~iaIs which llave so far been regulnrly used and contain hen-~y met..-lls, io(i;Ile and aldehydes nre no longer permitted or are being avoided to an ever increasing extent.
S}IO~'I` SUMMI\RY OF TIIE PRES13N'I` INVENTION.
Accordingly one object of the invention is to provide an aqueoIls solution which while hnv;n~,S a low protein error has a particIllarly high bactericidnl action while not, to any significant extent, being resorbed by the body even during prolonged administration for periods of several weeks. Therefore the solution is intencled to be more particularly applicable as a medicament with a bactericidal action for local wound treatment and to render possible the reduction of the use of additional systematic antibiotics or even to completely supplant them. For this purpose a high tissue wetting nction and a high tissue compatibility, comparable with that of Ringer's solution is necessary in the case of the solution in accordance with the invention.
Furthermore the solution is to be free of heavy metals, iodine, PVP and aldehydes and it is to rapidly con;bat the general effects of inflammation (fever, toxic phenomena) without the additional app]ication of antibiotics.
In accordance with the invention this aim is ach;eved since a lactate-free, pure Ringer's solution is employed, which in addition 2 ~ 7 (OntninS 0.1% 0l` M concer1trate, whi(h consists of ,1 20% a~]ul?o~ls solut;orl of 1~o1yhexamethylenebiguan(1idine hydrochk~ride, in wllic h 1 g of polymethyleneg1ycol with a moleculnr weight of appro?~imM1ely ~1~()00 is dissolve(l l-er 100 ml.
~\ mettlo~l for the proctuction of po1yhe~carllel;hyl(?rleb;gunrlic~in(?
hydrochlor;(le i~as been proposed ;n t he Germar1 patent specif;cal ion 1 ,G2û,938. I t has the rol1Owing formula:
~(CE1~ )6 -- NH -- C -- N~l -- C -- Nllln IlCl Nll Nlf n nnd is n1arlcetecl under the trade nnme of "Vantocil IB" by lmpericll Chem;cnl Indusl~ies Ltd as a surfaee dis;nrectant l`Or the fC)O(1SI;UffS~
brewing and soft dr;nks' industries. -- The polyethyleneglyco1 relevant for the lpresent pur1)ose is obtainable as "LUTROL E '1000" produced by BASF.
It was surprising that the solution ;n accordance W;tll the invent;on has a powerrul bacter;c;dal action, which ;s higtlly efficacious w;th respeet to all med;eally relevant baeter;a nnd fungi.
In this respect the solution in accordnnce Wit}l the ;nvent;on does not;
have any p~ote;n error ;n the pL~esence oE 2% Oe alb11m;n and ;n the presence of 20% WtlOle blood on1y hns a very low protein error.
In this respeet it is signi~iearlt thnt the so1ution in aecordance with the ;nvent;orl ;s not a d;s;nrectant of a convent;onal character, which for ;nstance for disinfecting the hands has to develop its fu11 effect within a short time of 30 seconds to 1 minute at the most. The solut;on in aeeordanee with the invention is not suitable ~or use as a skin disinfeetant sueh as one more part;icularly intended for prepar;ng for operat;ons.
It ;s the partieular merit oî the appl;can-t to have recogn;zed for the first time that the 1Ow concentrations of the selected b;guanidine of 0.1% ;n a pure, lactate-free Ringer's solut;ion leads to a resorption-free medicament for the treatment of wo~lnds with a high bacter;eidal aet;on and exeellent t;ssue eompatibil;ty, which even in i he presence of 20% whole blood has a praetieally negl;gible prote;n error and ;n the presenee of very low quantities of a eertain polyethyleneglycol has a surriciently high tissue wetting action so 2~394~7 ,~
t hnt ;n thc c nse of a su r~icierltly prolonge(l time of local a(llllinistrAt;orl lo an illrected wourld a sapro~)hytic microbial condit;or is achieved ~n(t it is even possible to achieve a sterile one.
The time Or a(tmin;stration of Ihe solution ;n accorclnnce with tlle invention to the pnthogenic orgnn;sms in ;nfected wounds alnollntæ lo at least 20 to 60 m;nutes. Even ;n the cnse Or treatment oî the WoUn( - fol~ per;ods of weeks there is no tenderlcy towarcls a decrease in the high degree Or cornpatib;lity. It has furthermore not ~een poss;ble to detect at any significant resorption of the sohltiorl in accor(llrlce wil h the inverlt;otl. It is only when the concentration level in accordance with the invention of 0~2Yo is exceeded that interference with the healing process in the wound is likely. Thus tesl s with a 0.4%
solut;on have shown that it is no longer suitable as a hactericidnl meAicament owing to ;ncompatibil;ty.
For normal admin;stration the concentration in accordance witl the inventioll of 0.1% is completely satisractory. It is only in e~cceptional cases and more particularly in the case of certa;n Gram negative organisms as more particularly occur ;n the buccs~l c nvity, that an increased concentration olF l;he b;guan;de used in ac(.or(tnllce with the invention of 0.2% ;s recomm~nnded, which however shoukl not be exceede(l. Even ;n the case of prolonged admirlistration to ;nfected wounds concentrnt;ons above 0.1% do nol; develop any sal ;sfactory bactericidal act;on.
1l\ decis;ve factor for the efE;cacy of the solut;on ;n accordance w;th the ;nvention is that ;t guarantees a decontam;nat;on of the ;nfected wound as far as a ster;le or saprophytic level, that then uneventful heal;ng may take place and that on further applicat;on of the solution in accordance with the invention to the wound the degree of decontamination achieved may be maintained so that the conditions for optimum healing of the wound are produced.
This makes particularly clear the character Or the solution in accordance with the invention as a medicament in contrast to conventional disinfectants, since the solution in accordance with the invention as a preparation for prolonged treatment ;nitially ensures a rapid and sufficient decontamination of the infected wounds as far as a saprophytic condition and maintains SUC}l action during the ent;ire period of healing if it is regularly applied or applied at intervals.
%~3~
ll~ n similal marlrler the solul.ion in nccordarlce with the inverltion acts as a prophylac.tic ror l he protection of woun(ls agninst renewecl in~ection cluring the entile healing process. Tn this case, as note(l, it is arl nclvarltnge in e~;cept;onal cases to use tlle somewhnt mol e concentrclte(l solution Or 0.2%.
Even ;n the cnse of prolonged admitlistration c>~ tl~(~ solut.ioll in accorc3ance with l;lle invention there are no signs of local irritat:;c)rl on the skin. The sol-ltion possesses a type of compatibility which is ~free of symptoms both locally and generally.
tO The solut;on in accordance with the ;nverltiotl has proved to be particlllarly advantageo-ls in the following cnses;
Irrigation Or wounds involv;ng acute and chronic bone and soft tissue infection;
Irrigation o~ sites of infection in order to able to perform the specific surgical treatment in an optimum, decontalllinal ed environment, SllCh as more particularly the insertion of free bone transplants (spongiosa) and however also stemmed so~t tiss~le nnc3 c)one transplan ts:
Wo~lnd irrigation during an opel al;ion, more particularly nlso ~for combatting microbes, which may become pathogenie after rel(?ase ;nl.o the opernt;on zone (hospitalism):
For covering over wourlds wh;ch are left open postoperatively, for instance with longuettes, which are impregnated with tlrle sohll;;on in accordanee with the invention:
Irrigation and use of tampons impregnated with the solution in accordance with the invention in dental surgery:
Postoperative irrigation in the case of operation sites liable to infection such as osteosyntheses, for the insertion and replacement of endoprostheses, for the treatment of wounds, in the case of injury to the wall of the abdomen and after the closure of the pertioneum.
While on the one hand being compatible and free o~F symptoms on the other hand at a coneentration of 0.1% the solution in accordance with the invention has proved to be effective preventively in the case of gastrie and intestinal resection and thernpeutieally in the case of cholecysisitis acuta after cholecyctectomy. In no single case c3id peritoneal complications (residual abscesses) occur. In this respect the irrigation quantity shou1d at the most only be equ~l to L000 ml.
2~39~
_ fi _ nr~ r igatiorl shoul(l not lasL longer tharl 15 lo 20 m;rlutes. l`heTl irrigntion with Ringer's sol~ltion shoulcl be performe(l. In the cnse of inl rna~(lominal irrigation with a limited quantity oF irrigntirlg sohltion it wns also found that no resorption took pklce. Sueh an ndrllinistration mny in exceptional cases be per~ormed with a 0.2%
solution in accordance with the invention. The intraab(lom;l-al administl ation of the solution in nccorclance with the inverlt;on thel efore offers ndvantages over iodophors as well, which OWillg to the ;odine related disorders are being less and less uscd for this pUl'pOSe.
t0 In the case of open irrigation and drairlage instillatiotl with l~inger's solution is interrupted l to 3 times and intermediate instillntion with the solutioll in accordance with the invention is performed .
Nulllerous tests have proved that even very heavil~y inPected wounds may he successEully treated with the solution in nccordance wit h the invention aE)plied only by itselE nnd locally. In this respecl ;i;
has been shown that the consumption of antibiotics m<l~y be substalll inll~
reduced in sceptic surgery. The intermitterlt use of the solution in acc:ordnnce with the invention with pure~ lactatefree l~inger's solution has in many cases proved t.o be particulnrly successful. 'I`he excellenl;
tissue and overall compatibility has led to oulstan(ling results in a Inrge nllmber Or ~ppl;cations, ;f ;nfected wouncls outs;de the abdomen nre covered 2 or 3 times daily for 20 to 60 minutes with, I`or ;nstance, gnu~e, which has been ;mpregnated w;th the solut;on in accordance w;th the invention. Aîter each such treatment there was post-;rrigation and further irrigation with pure lactatefree Ringer's solution.
Accordingly applications laster several weeks were quite common.
It was furthermore poss;ble to show that ;n the case of a ser;es of local osteitis cases the signs of local in~lammation dim;nished surprisingly quickly if already existing passages (fistulae) leading to the sites of ;nfection are irrigated with a sollltion in accordance with the ;nvention at a concentration of 0.1%. Then, more part;cularly, there was even a d;sappearance of the pungent odor produced in the case of Pseudomonas aerugillosa.
A further observation made was that in the case of the administration of the solution in accordance with the ;nvention general effects (fever, toxic phenomena) quickly d;ed down even if no 203~
systeIl~at;c arll ibi tics we re applied.
Sometl~ing th lt was more particularly :imp.ress;ve was l he decontamintlt;rlg act;on of the solution ;n accordnnce with the ;nver tion in the case o~ s;tes of ir :rect;or wh;ch w;thout curett.age were irrigated nlong wil;h their necrotic content and became sterill?
something that was not e~cperienced ;n the casc of irrigation wil;h antibiotics.
Owing to its avaskularity the spongiosa const;tutes a particulnrly nice criter;on in order to demonstrate the advantageous effects of the sohltion in nccordance w;th the invention wllen nppl;ed to the demand;ng procedure of settling a spongiosa transplanl;. Thus in the case of a number of spongiosa cases when the solutiorl in accordarlce with the invention was applied the spongiosa inlays were able to be settled completely quantitatively. The reliable settlement oï the spongiosa both in the host bed and also in the case o-~ treatment Or nn open wourld mny be looked upon as a reliable indication that the dressing of the wounds with gauze soaked in a solution in nccord~llce Witll the ;nvention not only lends to an oE)timum degree of decorltaminatiorl but means that such decolltaminat ion may ~)e mRi1lt.~ d for a long period o~ tinle. Tllis means that the significant conclitions for trollble-free settlement of the spongiosa inlays are produced that is to say l he certain prevention of infection and of the resulting interference with revascularization of the spongiosa structure. :tn no single cnse was there found to be rejection of spongiosa parts and furthermore the uninterrupted wetting of the wounds with the solution in accordance with the invention did not impair the process of recovery in the least respect. Last but not least the solution in accorclance with the invention has been able to perform the task of adequate wound rmoistening.
Even in the case of a sufficiently stabile corticalis subject to debridement and which was as such lef t open it was possible by USillg gauze soaked in the solution to keep up a deg~e( of decontamination which in all cases led to a spontane~ )us closure of the wound provided that the shrinkage capacity of the soft tissues was adequate.
Bacteriological smears taken from l;he wounds~ which were left open after -the operation showed a l~igh degree of agreement with the 2~39~ ~
clinically as~ me(l degree of decontamirlation. [n the ctlse of ~hree-q~n~l,ers o~ nll s~ ongiosn patient;s even l,he f;rst postol erat;ve woull~l smears or mal,erial obtained by SUCtiOIl dra;nage were s~,erile: ;1'1 the case of col~t;cnlis pclt,ients the Pracl.ion was four-fifths.
:; In tlle case of the othel patierlts the smears were firstly positive bul, then became negative later. 'I`his WAS usunll~r the case with wourlds, in the case of which the self-cleansing OI t,he g1~anulntion was delnyed. In this respect it is significant that in the case oï
such wounds the settlement of the left-open spongiosa or cort;calis took place j~lst as ulleventfully as ;n the case of clean granulations.
In a group of 50 cases which were treate~ with the solu tiorl in accordnnce with the ;nvention (involving irrigation of the sil,es of infection in preparatory stage, covering the postoperative wounds with longuettes soaked in the sohltioll] the following pathogens were t5 eliminated with different times of action:
Staph. aureus various Strel~tococci (Enterococci) Closl.ridium sphenoicles Pseudomonas nerugillosa Serratus marcescells S taph . e pidermidis E. coli Prol;eus margani and P. vulgaris }~lebsiella spp.
~erormonas hydrophilia anaerobic Corynebacteria Achromobacter agglomerans Further experience was gained during the treatment of acute soft tissue phlegmon conditions in the case of which the formation of an abscess was hardly restricted or not restricted at all. The lanced sites of infection were irrigated for a short time using a bhlnt tube and the sol-ltion in accordance with the invention. The decontamination and the consequent decrease in local and general signs oP inPIammation took place surprisingly rapidly. The pathogens generally disappeared from the incisions, which were treated with longuettes soake(t in the solution, after only a few days. l~ccordingly the solution ;n accordance with the invention may be considered to have a deep action.
- ~03~7 ~, Ille solllliol-l in accol(larlce wilh the invelltioll thlls constit-lles an e~ficnciolls alllisel-tic in Ihe sense Ihal it is a bnc:leric idnl nlld l issue-oml-ntil~le nd juvnnt for the trenl;merlt. of woun(ls more l-a~liculnrly in tlle sllrgical repair of ac~lte ~n~l chronic ;nîec~lions of bOlle cll~d soft t iss~le~ suc h treatmenl. Frequenl;ly proving ~ ccessf~ll even wilho~lt l he ndlll;n;sl r<ltion of systerllAt;c antib;ol.;cs.
Owing to Ihe relinble bactericidlal action, the erre( tive local and symptom-free general con-l~atibility of the sol~ltion in nccordarlce with the invent;on Ihere can be no objection to tl~e use thereof for the prophylact;c irr;gatiorl of wounds. This ;s tr~le both or intra.~bdominal irrigation and also for the irrigation of other parts of l he body.
The sol~lt ic~n ;n accordance w;th the invent;on however only develops ;ts opt;mum and successflll efect if the bas;c principles of surgical treatment (vasculal ity and stability~ are adhered to.
IN T1113 P~\TENT OFFICE OE~ T}IE UNIT13D S l`i~ l'E~
--A RINGER'S SOLUTION--13ACKGI~OIJND OF TIIE INVENTION.
The invention relates to a lactate-rree pure R;nger's solut;on with additives which make it suitable for the decontnmination of woun(ls so that their c onclition is sterile or saprophytic and for maintaining such a condition during the entire healing process.
The invention is more part;cularly intcndecl to prov;de a Ringer's solution with such additives that it is equnlly suitable as a medicament with bactericidal properties applied in thel~apeutic meLhods for the local treatment of infected wounds, for the local prol hylatic treatnlent of wounds liable to become infected more particulm~ly du~ lg nn operation an~i for local decontamirlation Or wounds to free them of bacteria durillg the process o~ healing.
t5 A large number o~ wound treatment materials are known which however are not completely satisfactory or are unsuitable for application as medicaments owing to insufficient compatibility with the body tissues, their high protein error (i. e. to impairment of the bactericidal action in the presence of protein, as for instance wound e~udation and blood), their partly insufficient bactericidal action and their disadvantageous property of being resorbed by the body in greater or lesser quantities. A further point to be considered is that the tissue compatibility of such materials is frequently is not sul`ficient - owing to an e~cessive surface tension.
The administration of iodophors for the treatment o.f wounds involves the danger of resorption of iodine and thus the possibility of iodine-induced disorders. Furthermore iodophors have a significant protein error. With a iodophor dilution of 1:10 it is still possible, 203~
.he IaboI iIl;ory~ to I)ro(luce n good bactericidal action, whi(.dl llowever in the presence of 20% oï whole blood ;s more or less compIetely carIcelecI ouI. Owing lo the hazard of poterlti.tll~y fntal postopeI~ntive shock con(lit;iorIs the i~Itrnabdominal admin;strat;orl of iodoI)tloI~s h(ls been coml-IeteIy abandone(l, II~ ;ts action chlorhexidine is essentially solely bacteriostatic anà is no longer recommended for local wound treatrlIent;.
It is frequentIy objected that operation wounds are not able to be sufficierltIy protected against pathogenic organisms which are nlways able to perva(le the wound or which are present in the body ns ben;gn microorganisms in the body and nre only rendered pathogenic by the operation.
The infection haæard in the case of operations is therefore still nppreciable, Ihis hnving a connection with the incrensing resistance to antibiotics. A further point to be considered is ttlaI;
owing to the danger of serious side-effects woIlnd trentIllerlt mrlI eI~iaIs which llave so far been regulnrly used and contain hen-~y met..-lls, io(i;Ile and aldehydes nre no longer permitted or are being avoided to an ever increasing extent.
S}IO~'I` SUMMI\RY OF TIIE PRES13N'I` INVENTION.
Accordingly one object of the invention is to provide an aqueoIls solution which while hnv;n~,S a low protein error has a particIllarly high bactericidnl action while not, to any significant extent, being resorbed by the body even during prolonged administration for periods of several weeks. Therefore the solution is intencled to be more particularly applicable as a medicament with a bactericidal action for local wound treatment and to render possible the reduction of the use of additional systematic antibiotics or even to completely supplant them. For this purpose a high tissue wetting nction and a high tissue compatibility, comparable with that of Ringer's solution is necessary in the case of the solution in accordance with the invention.
Furthermore the solution is to be free of heavy metals, iodine, PVP and aldehydes and it is to rapidly con;bat the general effects of inflammation (fever, toxic phenomena) without the additional app]ication of antibiotics.
In accordance with the invention this aim is ach;eved since a lactate-free, pure Ringer's solution is employed, which in addition 2 ~ 7 (OntninS 0.1% 0l` M concer1trate, whi(h consists of ,1 20% a~]ul?o~ls solut;orl of 1~o1yhexamethylenebiguan(1idine hydrochk~ride, in wllic h 1 g of polymethyleneg1ycol with a moleculnr weight of appro?~imM1ely ~1~()00 is dissolve(l l-er 100 ml.
~\ mettlo~l for the proctuction of po1yhe~carllel;hyl(?rleb;gunrlic~in(?
hydrochlor;(le i~as been proposed ;n t he Germar1 patent specif;cal ion 1 ,G2û,938. I t has the rol1Owing formula:
~(CE1~ )6 -- NH -- C -- N~l -- C -- Nllln IlCl Nll Nlf n nnd is n1arlcetecl under the trade nnme of "Vantocil IB" by lmpericll Chem;cnl Indusl~ies Ltd as a surfaee dis;nrectant l`Or the fC)O(1SI;UffS~
brewing and soft dr;nks' industries. -- The polyethyleneglyco1 relevant for the lpresent pur1)ose is obtainable as "LUTROL E '1000" produced by BASF.
It was surprising that the solution ;n accordance W;tll the invent;on has a powerrul bacter;c;dal action, which ;s higtlly efficacious w;th respeet to all med;eally relevant baeter;a nnd fungi.
In this respect the solution in accordnnce Wit}l the ;nvent;on does not;
have any p~ote;n error ;n the pL~esence oE 2% Oe alb11m;n and ;n the presence of 20% WtlOle blood on1y hns a very low protein error.
In this respeet it is signi~iearlt thnt the so1ution in aecordance with the ;nvent;orl ;s not a d;s;nrectant of a convent;onal character, which for ;nstance for disinfecting the hands has to develop its fu11 effect within a short time of 30 seconds to 1 minute at the most. The solut;on in aeeordanee with the invention is not suitable ~or use as a skin disinfeetant sueh as one more part;icularly intended for prepar;ng for operat;ons.
It ;s the partieular merit oî the appl;can-t to have recogn;zed for the first time that the 1Ow concentrations of the selected b;guanidine of 0.1% ;n a pure, lactate-free Ringer's solut;ion leads to a resorption-free medicament for the treatment of wo~lnds with a high bacter;eidal aet;on and exeellent t;ssue eompatibil;ty, which even in i he presence of 20% whole blood has a praetieally negl;gible prote;n error and ;n the presenee of very low quantities of a eertain polyethyleneglycol has a surriciently high tissue wetting action so 2~394~7 ,~
t hnt ;n thc c nse of a su r~icierltly prolonge(l time of local a(llllinistrAt;orl lo an illrected wourld a sapro~)hytic microbial condit;or is achieved ~n(t it is even possible to achieve a sterile one.
The time Or a(tmin;stration of Ihe solution ;n accorclnnce with tlle invention to the pnthogenic orgnn;sms in ;nfected wounds alnollntæ lo at least 20 to 60 m;nutes. Even ;n the cnse Or treatment oî the WoUn( - fol~ per;ods of weeks there is no tenderlcy towarcls a decrease in the high degree Or cornpatib;lity. It has furthermore not ~een poss;ble to detect at any significant resorption of the sohltiorl in accor(llrlce wil h the inverlt;otl. It is only when the concentration level in accordance with the invention of 0~2Yo is exceeded that interference with the healing process in the wound is likely. Thus tesl s with a 0.4%
solut;on have shown that it is no longer suitable as a hactericidnl meAicament owing to ;ncompatibil;ty.
For normal admin;stration the concentration in accordance witl the inventioll of 0.1% is completely satisractory. It is only in e~cceptional cases and more particularly in the case of certa;n Gram negative organisms as more particularly occur ;n the buccs~l c nvity, that an increased concentration olF l;he b;guan;de used in ac(.or(tnllce with the invention of 0.2% ;s recomm~nnded, which however shoukl not be exceede(l. Even ;n the case of prolonged admirlistration to ;nfected wounds concentrnt;ons above 0.1% do nol; develop any sal ;sfactory bactericidal act;on.
1l\ decis;ve factor for the efE;cacy of the solut;on ;n accordance w;th the ;nvention is that ;t guarantees a decontam;nat;on of the ;nfected wound as far as a ster;le or saprophytic level, that then uneventful heal;ng may take place and that on further applicat;on of the solution in accordance with the invention to the wound the degree of decontamination achieved may be maintained so that the conditions for optimum healing of the wound are produced.
This makes particularly clear the character Or the solution in accordance with the invention as a medicament in contrast to conventional disinfectants, since the solution in accordance with the invention as a preparation for prolonged treatment ;nitially ensures a rapid and sufficient decontamination of the infected wounds as far as a saprophytic condition and maintains SUC}l action during the ent;ire period of healing if it is regularly applied or applied at intervals.
%~3~
ll~ n similal marlrler the solul.ion in nccordarlce with the inverltion acts as a prophylac.tic ror l he protection of woun(ls agninst renewecl in~ection cluring the entile healing process. Tn this case, as note(l, it is arl nclvarltnge in e~;cept;onal cases to use tlle somewhnt mol e concentrclte(l solution Or 0.2%.
Even ;n the cnse of prolonged admitlistration c>~ tl~(~ solut.ioll in accorc3ance with l;lle invention there are no signs of local irritat:;c)rl on the skin. The sol-ltion possesses a type of compatibility which is ~free of symptoms both locally and generally.
tO The solut;on in accordance with the ;nverltiotl has proved to be particlllarly advantageo-ls in the following cnses;
Irrigation Or wounds involv;ng acute and chronic bone and soft tissue infection;
Irrigation o~ sites of infection in order to able to perform the specific surgical treatment in an optimum, decontalllinal ed environment, SllCh as more particularly the insertion of free bone transplants (spongiosa) and however also stemmed so~t tiss~le nnc3 c)one transplan ts:
Wo~lnd irrigation during an opel al;ion, more particularly nlso ~for combatting microbes, which may become pathogenie after rel(?ase ;nl.o the opernt;on zone (hospitalism):
For covering over wourlds wh;ch are left open postoperatively, for instance with longuettes, which are impregnated with tlrle sohll;;on in accordanee with the invention:
Irrigation and use of tampons impregnated with the solution in accordance with the invention in dental surgery:
Postoperative irrigation in the case of operation sites liable to infection such as osteosyntheses, for the insertion and replacement of endoprostheses, for the treatment of wounds, in the case of injury to the wall of the abdomen and after the closure of the pertioneum.
While on the one hand being compatible and free o~F symptoms on the other hand at a coneentration of 0.1% the solution in accordance with the invention has proved to be effective preventively in the case of gastrie and intestinal resection and thernpeutieally in the case of cholecysisitis acuta after cholecyctectomy. In no single case c3id peritoneal complications (residual abscesses) occur. In this respect the irrigation quantity shou1d at the most only be equ~l to L000 ml.
2~39~
_ fi _ nr~ r igatiorl shoul(l not lasL longer tharl 15 lo 20 m;rlutes. l`heTl irrigntion with Ringer's sol~ltion shoulcl be performe(l. In the cnse of inl rna~(lominal irrigation with a limited quantity oF irrigntirlg sohltion it wns also found that no resorption took pklce. Sueh an ndrllinistration mny in exceptional cases be per~ormed with a 0.2%
solution in accordance with the invention. The intraab(lom;l-al administl ation of the solution in nccorclance with the inverlt;on thel efore offers ndvantages over iodophors as well, which OWillg to the ;odine related disorders are being less and less uscd for this pUl'pOSe.
t0 In the case of open irrigation and drairlage instillatiotl with l~inger's solution is interrupted l to 3 times and intermediate instillntion with the solutioll in accordance with the invention is performed .
Nulllerous tests have proved that even very heavil~y inPected wounds may he successEully treated with the solution in nccordance wit h the invention aE)plied only by itselE nnd locally. In this respecl ;i;
has been shown that the consumption of antibiotics m<l~y be substalll inll~
reduced in sceptic surgery. The intermitterlt use of the solution in acc:ordnnce with the invention with pure~ lactatefree l~inger's solution has in many cases proved t.o be particulnrly successful. 'I`he excellenl;
tissue and overall compatibility has led to oulstan(ling results in a Inrge nllmber Or ~ppl;cations, ;f ;nfected wouncls outs;de the abdomen nre covered 2 or 3 times daily for 20 to 60 minutes with, I`or ;nstance, gnu~e, which has been ;mpregnated w;th the solut;on in accordance w;th the invention. Aîter each such treatment there was post-;rrigation and further irrigation with pure lactatefree Ringer's solution.
Accordingly applications laster several weeks were quite common.
It was furthermore poss;ble to show that ;n the case of a ser;es of local osteitis cases the signs of local in~lammation dim;nished surprisingly quickly if already existing passages (fistulae) leading to the sites of ;nfection are irrigated with a sollltion in accordance with the ;nvention at a concentration of 0.1%. Then, more part;cularly, there was even a d;sappearance of the pungent odor produced in the case of Pseudomonas aerugillosa.
A further observation made was that in the case of the administration of the solution in accordance with the ;nvention general effects (fever, toxic phenomena) quickly d;ed down even if no 203~
systeIl~at;c arll ibi tics we re applied.
Sometl~ing th lt was more particularly :imp.ress;ve was l he decontamintlt;rlg act;on of the solution ;n accordnnce with the ;nver tion in the case o~ s;tes of ir :rect;or wh;ch w;thout curett.age were irrigated nlong wil;h their necrotic content and became sterill?
something that was not e~cperienced ;n the casc of irrigation wil;h antibiotics.
Owing to its avaskularity the spongiosa const;tutes a particulnrly nice criter;on in order to demonstrate the advantageous effects of the sohltion in nccordance w;th the invention wllen nppl;ed to the demand;ng procedure of settling a spongiosa transplanl;. Thus in the case of a number of spongiosa cases when the solutiorl in accordarlce with the invention was applied the spongiosa inlays were able to be settled completely quantitatively. The reliable settlement oï the spongiosa both in the host bed and also in the case o-~ treatment Or nn open wourld mny be looked upon as a reliable indication that the dressing of the wounds with gauze soaked in a solution in nccord~llce Witll the ;nvention not only lends to an oE)timum degree of decorltaminatiorl but means that such decolltaminat ion may ~)e mRi1lt.~ d for a long period o~ tinle. Tllis means that the significant conclitions for trollble-free settlement of the spongiosa inlays are produced that is to say l he certain prevention of infection and of the resulting interference with revascularization of the spongiosa structure. :tn no single cnse was there found to be rejection of spongiosa parts and furthermore the uninterrupted wetting of the wounds with the solution in accordance with the invention did not impair the process of recovery in the least respect. Last but not least the solution in accorclance with the invention has been able to perform the task of adequate wound rmoistening.
Even in the case of a sufficiently stabile corticalis subject to debridement and which was as such lef t open it was possible by USillg gauze soaked in the solution to keep up a deg~e( of decontamination which in all cases led to a spontane~ )us closure of the wound provided that the shrinkage capacity of the soft tissues was adequate.
Bacteriological smears taken from l;he wounds~ which were left open after -the operation showed a l~igh degree of agreement with the 2~39~ ~
clinically as~ me(l degree of decontamirlation. [n the ctlse of ~hree-q~n~l,ers o~ nll s~ ongiosn patient;s even l,he f;rst postol erat;ve woull~l smears or mal,erial obtained by SUCtiOIl dra;nage were s~,erile: ;1'1 the case of col~t;cnlis pclt,ients the Pracl.ion was four-fifths.
:; In tlle case of the othel patierlts the smears were firstly positive bul, then became negative later. 'I`his WAS usunll~r the case with wourlds, in the case of which the self-cleansing OI t,he g1~anulntion was delnyed. In this respect it is significant that in the case oï
such wounds the settlement of the left-open spongiosa or cort;calis took place j~lst as ulleventfully as ;n the case of clean granulations.
In a group of 50 cases which were treate~ with the solu tiorl in accordnnce with the ;nvention (involving irrigation of the sil,es of infection in preparatory stage, covering the postoperative wounds with longuettes soaked in the sohltioll] the following pathogens were t5 eliminated with different times of action:
Staph. aureus various Strel~tococci (Enterococci) Closl.ridium sphenoicles Pseudomonas nerugillosa Serratus marcescells S taph . e pidermidis E. coli Prol;eus margani and P. vulgaris }~lebsiella spp.
~erormonas hydrophilia anaerobic Corynebacteria Achromobacter agglomerans Further experience was gained during the treatment of acute soft tissue phlegmon conditions in the case of which the formation of an abscess was hardly restricted or not restricted at all. The lanced sites of infection were irrigated for a short time using a bhlnt tube and the sol-ltion in accordance with the invention. The decontamination and the consequent decrease in local and general signs oP inPIammation took place surprisingly rapidly. The pathogens generally disappeared from the incisions, which were treated with longuettes soake(t in the solution, after only a few days. l~ccordingly the solution ;n accordance with the invention may be considered to have a deep action.
- ~03~7 ~, Ille solllliol-l in accol(larlce wilh the invelltioll thlls constit-lles an e~ficnciolls alllisel-tic in Ihe sense Ihal it is a bnc:leric idnl nlld l issue-oml-ntil~le nd juvnnt for the trenl;merlt. of woun(ls more l-a~liculnrly in tlle sllrgical repair of ac~lte ~n~l chronic ;nîec~lions of bOlle cll~d soft t iss~le~ suc h treatmenl. Frequenl;ly proving ~ ccessf~ll even wilho~lt l he ndlll;n;sl r<ltion of systerllAt;c antib;ol.;cs.
Owing to Ihe relinble bactericidlal action, the erre( tive local and symptom-free general con-l~atibility of the sol~ltion in nccordarlce with the invent;on Ihere can be no objection to tl~e use thereof for the prophylact;c irr;gatiorl of wounds. This ;s tr~le both or intra.~bdominal irrigation and also for the irrigation of other parts of l he body.
The sol~lt ic~n ;n accordance w;th the invent;on however only develops ;ts opt;mum and successflll efect if the bas;c principles of surgical treatment (vasculal ity and stability~ are adhered to.
Claims (9)
1 A lactate-free Ringer's solution which additionally contains 0.1% of a concentrate, which consists of a 20% aqueous solution of polyhexamethylene biguanidine hydrochloride, in which for every 100 ml. 1 g of polyethyleneglycol which a molecular weight of approximately 4,000 is dissolved.
2 The Ringer's solution as claimed on claim I adapted for the local bacterial decontamination of wounds to attain a sterile or saprophytic condition.
3 The Ringer's solution as claimed in claim 1, adapted for the maintenance of a sterile or saprophytic condition during the entire treatment period
4 The Ringer's solution as claimed in claim 2, comprising a concentration increased to 0.2% at the maximum for the decontamination to eliminate Gram negative pathogens (such as for instance Pseudomonas) and/or anaerobes.
The Ringer's solution as claimed in claim 1 adapted for use as a bactericidally effective medicament for application in the case of therapeutic methods for the local treatment of infected wounds.
6 The Ringer's solution as claimed in claim 1 adapted for use as a bactericidally effective medicament for the prophylactic treatment of wounds liable to become infected.
7 The Ringer's solution as claimed in claim 1 adapted for the prophylactic treatment of wounds likely to become infected, such treatment being performed during an operation.
8 The Ringer's solution as claimed in claim 1 adapted for use as a bactericidally acting medicament in order to ensure local bacterial decontamination of wounds during the process of healing.
9 The Ringer's solution as claimed in claim 1 adapted for the impregnation of wound dressings such as gauze, tampons, longuettes and synthetic resin materials.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP90106312.2 | 1990-04-02 | ||
| EP90106312A EP0450117A1 (en) | 1990-04-02 | 1990-04-02 | Ringers solution and its use as a bactericidally active local wound-treatment medicament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2039457A1 true CA2039457A1 (en) | 1991-10-03 |
Family
ID=8203853
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2039457 Abandoned CA2039457A1 (en) | 1990-04-02 | 1991-03-28 | Ringer's solution |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP0450117A1 (en) |
| CA (1) | CA2039457A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3231452A1 (en) | 2016-04-11 | 2017-10-18 | DiCosmo, Frank | Wound irrigation solutions |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2122288T3 (en) * | 1993-05-26 | 1998-12-16 | Fresenius Ag | ANTI-INFECTIOUS. |
| GB9506841D0 (en) * | 1995-04-03 | 1995-05-24 | Unilever Plc | Deodorant compositions |
| GB9512290D0 (en) * | 1995-06-16 | 1995-08-16 | Moorfields Eye Hospital | Uses of polyhexanide |
| DE19604475A1 (en) * | 1996-02-08 | 1997-08-14 | Fresenius Ag | Use of PHMB to treat infections caused by intracellular proliferative agents |
| DE19628641C2 (en) * | 1996-07-16 | 1998-12-17 | Fresenius Ag | Use of PHMB for the treatment of tumor diseases |
| AU6247299A (en) * | 1998-09-11 | 2000-04-03 | Surfacine Development Company, Llc | Topical dermal antimicrobial compositions |
| US20040204496A1 (en) * | 2003-04-11 | 2004-10-14 | Ammon Daniel M. | Disinfecting solutions effective against bacterial endospores |
| DE10332680A1 (en) * | 2003-07-18 | 2005-02-17 | Biomet Deutschland Gmbh | Use of antiseptic agents in PMMA bone cements |
| BRPI0510004A (en) * | 2004-04-20 | 2007-09-18 | Univ Chicago | article of manufacture, methods for administering a therapeutic composition to an individual's epithelium, to treat a microbe-mediated condition of an individual's epithelium, to ameliorate a symptom of a condition and to prevent a condition, and to use compound type peg pma |
| DE102004024140A1 (en) | 2004-05-14 | 2005-12-08 | Fresenius Medical Care Deutschland Gmbh | Preservative for medical devices |
| DE102007030931A1 (en) * | 2007-07-03 | 2009-01-08 | Birgit Riesinger | Composition containing at least one nutritive, at least one disinfecting or decontaminating and / or at least one protease inhibiting active substance and / or active substance complex |
| WO2011123665A1 (en) * | 2010-03-31 | 2011-10-06 | Biolife Solutions, Inc. | Methods and compositions for the treatment of burns and wounds |
| WO2013135571A1 (en) | 2012-03-14 | 2013-09-19 | Orphanidis Pharma Research Gmbh | Compositions with enhanced therapeutic efficacy against infective agents of the eye comprising miltefosine and polyhexamethylene biguanide |
| EP2896396A1 (en) | 2014-01-20 | 2015-07-22 | Abem Kimya Tibbi Malzemeler Yönetim Danismanligi Temizlik Servis Hizmetleri Sanayi Ve Dis Ticaret Limited Sirketi | Herbal formulation for topical wound treatment |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1167249A (en) * | 1967-08-18 | 1969-10-15 | Ici Ltd | Polymeric Diguanides |
| DE3537627C2 (en) * | 1984-11-03 | 1995-01-26 | Infectless S A | Disinfectant and its use |
-
1990
- 1990-04-02 EP EP90106312A patent/EP0450117A1/en not_active Ceased
-
1991
- 1991-03-28 CA CA 2039457 patent/CA2039457A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3231452A1 (en) | 2016-04-11 | 2017-10-18 | DiCosmo, Frank | Wound irrigation solutions |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0450117A1 (en) | 1991-10-09 |
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