DK164198B

DK164198B - Topical preparation comprising ether for treating herpes simplex virus

Info

Publication number: DK164198B
Application number: DK88384A
Authority: DK
Inventors: Harvey T Collins
Original assignee: Harvey T Collins
Priority date: 1984-02-22
Filing date: 1984-02-22
Publication date: 1992-05-25
Also published as: DK88384A; DK164198C; DK88384D0

Description

iin

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Den foreliggende opfindelse angår et topisk præparat til påføring af områder på menneskets krop, som er inficeret med herpes simplex virus, til inaktivering af virusen.The present invention relates to a topical composition for applying areas of the human body infected with herpes simplex virus to inactivating the virus.

Der findes to typer herpes simplex virus, der bevirker forskellige 5 former for kliniske udslag. I almindelighed er herpes simplex type 1 forbundet med periodisk tilbagevendende labial is (forkølelsessår), og herpes simplex type 2 er forbundet med periodisk tilbagevendende vulvovaginitis.There are two types of herpes simplex virus that cause different 5 types of clinical rashes. In general, herpes simplex type 1 is associated with periodic recurrent labial ice (cold sores) and herpes simplex type 2 is associated with periodic recurrent vulvovaginitis.

Herpes simplex virus synes at finde at de porøse områder omkring 10 slimhinderne er et attraktivt sted at trives og forårsage infektion.Herpes simplex virus seems to find that the porous areas around the 10 mucous membranes are an attractive place to thrive and cause infection.

Når først et uskadt område er angrebet af herpes simplex virus, ser der ud til at være en triggermekanisme, der tager imod gentaget infektion af det samme område. Grunden til dette fænomen er endnu ikke kendt.Once an uninfected area is attacked by herpes simplex virus, there appears to be a trigger mechanism that takes on repeated infection of the same area. The cause of this phenomenon is not yet known.

Herpes simplex virus' infektivitet er hovedsageligt afhængig af den 15 virale kappes uberørthed, og en kemisk forbindelse, der skader eller fjerner kappen, vil reducere infektiviteten stærkt. Det er velkendt, at ether er særdeles velegnet til tilvejebringelse af denne effekt. Den normale kropstemperatur er imidlertid ca. 4*C over kogepunktet for ethylether, således at behandling in vivo hidtil ikke har været 20 vellykket. Se for eksempel "Topical Ether and Herpes Simplex Labial is" af Mary E. Guinan, M.D., Ph.D, et al., JAMA, 14. marts 1980, vol. 243, nr. 10, side 1059-61. Ligeledes på grund af ethers meget store flygtighed, i særdeleshed ethylether, ved stuetemperatur eller derover, har ethylether hidtil kun været anvendt til denne type behandling i et kon-25 trolleret miljø såsom på et hospital eller hos en praktiserende læge, og ethylether har ikke været tilgængelig i en form, som var egnet til anvendelse uden for et kontrolleret (for eksempel hospitals-) miljø.The infectivity of the herpes simplex virus is mainly dependent on the untouched viral coat, and a chemical compound that damages or removes the coat will greatly reduce the infectivity. It is well known that ether is particularly suitable for providing this effect. However, the normal body temperature is approx. 4 ° C above the boiling point of ethyl ether, so that in vivo treatment so far has not been successful. See, for example, "Topical Ether and Herpes Simplex Labial Ice" by Mary E. Guinan, M.D., Ph.D., et al., JAMA, March 14, 1980, Vol. 243, No. 10, pages 1059-61. Also, due to the very high volatility of ethers, in particular ethyl ether, at room temperature or above, ethyl ether has so far been used only for this type of treatment in a controlled environment such as in a hospital or GP, and ethyl ether has not been used. available in a form suitable for use outside a controlled (e.g., hospital) environment.

I stedet har ether-, amid- eller esterbundne forbindelser alene eller i kombination været anvendt. Sådanne forbindelsers effektivitet 30 til behandling af Herpes simplex virus er imidlertid langt mindre end ren ethers. Et eksempel på en emulsion indeholdende en sådan forbindelse er omhandlet i US-patentskrift nr. 4.020.183.Instead, ether-, amide- or ester-bound compounds alone or in combination have been used. However, the effectiveness of such compounds in treating Herpes simplex virus is far less than pure ether. An example of an emulsion containing such a compound is disclosed in U.S. Patent No. 4,020,183.

I overensstemmelse med dette patentskrift applikeres ikke-ioniske overfladeaktive midler i en ikke-irriterende bærer så som en lotion 35 eller olie til et inficeret område, idet den anvendte mængde overfladeaktivt middel ligger mellem 0,5 og 20 volumenprocent.In accordance with this patent, nonionic surfactants are applied in a non-irritating carrier such as a lotion 35 or oil to an infected area, the amount of surfactant used being between 0.5 and 20% by volume.

I Biological Abstracts vol. 73, no. 2, 1982, nr. 11154 er det beskrevet at ethylether applikeret topisk på tilbagevendende herpes 2In Biological Abstracts, vol. 73, no. 2, 1982, No. 11154, it is disclosed that ethyl ether applied topically to recurrent herpes 2

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simplex infektioner, forlænger intervallet mellem virusudbrud.simplex infections, prolong the interval between virus outbreaks.

I US-patentskrift nr. 3.949.071 er det blevet foreslået at anvende en vandig opløsning omfattende en base, fedtsyrer hovedsageligt bestående af oleinsyre og et overfladeaktivt middel til behandling af 5 brandsår, skoldninger og andre hudirritationer. Basen er et al kalimetal-carbonat.In U.S. Patent No. 3,949,071, it has been proposed to use an aqueous solution comprising a base, fatty acids consisting mainly of oleic acid and a surfactant for the treatment of 5 burns, scars and other skin irritations. The base is an all potassium carbonate.

I US-patentskrift nr. 2.079.166 er det yderligere blevet foreslået at anvende et topisk præparat bestående af en blød sæbe og stearoptener i en salve til anvendelse som et liniment.In U.S. Patent No. 2,079,166, it has further been proposed to use a topical composition consisting of a soft soap and stearoptener in an ointment for use as a liniment.

10 Endvidere er det kendt fra "A simple proof of the thermodynamic stability of materials taken up by solutions containing solubilizers such as soap", Amer. Chem. Soc. 62, 2855-9 (1940), at ether er termodynamisk stabilt i sæbe. Især er de kolloide opløsninger, der er dannet af en opløsning af ether og sæbe, som indeholder små mængder silikat 15 eller hydroxid, termodynamisk stabile, på grund af at damptrykket er signifikant mindre end for det fri carbonhydrids vedkommende, indtil opløsningen er næsten mættet.Furthermore, it is known from "A simple proof of the thermodynamic stability of materials taken up by solutions containing solubilizers such as soap", Amer. Chem. Soc. 62, 2855-9 (1940), that ether is thermodynamically stable in soap. In particular, the colloidal solutions formed from a solution of ether and soap containing small amounts of silicate 15 or hydroxide are thermodynamically stable because the vapor pressure is significantly less than that of the free hydrocarbon until the solution is almost saturated.

Endvidere er det kendt fra "SOAP MANUFACTURE" af J. Davidsohn, et al., udgivet af Interscience Publishers, Inc. New York, side 495, at 20 kokosnødoliesæbe var mere bakteriedræbende overfor Escherichia col i og Eberthella typhosa end andre sæber, som er fremstillet ud fra naturlige fedtstoffer og olier. Det omtales ligeledes i denne tekst på side 503, at kultjæresæber kan fremstilles ved tilsætning af trætjære til kokos-nødoliesæbe, og på side 505, at svovlsæbe kan fremstilles ved tilsætning 25 af svovl til kokosnødoliesæbe.Furthermore, it is known from "SOAP MANUFACTURE" by J. Davidsohn, et al., Published by Interscience Publishers, Inc. New York, page 495 that 20 coconut oil soaps were more bactericidal to Escherichia col i and Eberthella typhosa than other soaps made from natural fats and oils. It is also mentioned in this text on page 503 that coal tar soaps can be prepared by the addition of wooden tar to coconut oil soap, and on page 505 that sulfur soap can be produced by the addition of sulfur to coconut oil soap.

Som det vil blive beskrevet mere detaljeret i det efterfølgende, afviger det topiske præparat ifølge den foreliggende opfindelse fra de tidligere foreslåede præparater ved, at det indeholder en blanding af vandfri ethylether (frem for en bundet forbindelse), hvori den anvendte 30 mængde vandfri ethylether omfatter mindst 30 volumenprocent af blandingen, og en oliebærer, fortrinsvis en kokosnødoliebærer. Desuden benytter blandingen en kokosnødoliebærer med færrest mulige frie fedtsyrer.As will be described in more detail below, the topical composition of the present invention differs from the previously proposed compositions in that it contains a mixture of anhydrous ethyl ether (rather than a bonded compound) wherein the amount of anhydrous ethyl ether used comprises at least 30% by volume of the mixture, and an oil carrier, preferably a coconut oil carrier. In addition, the mixture uses a coconut oil carrier with the least possible free fatty acids.

I overensstemmelse med opfindelsen tilvejebringes et topisk præparat til behandling af et epidermisområde på et menneske inficeret 35 med herpes simplex virus, hvilket præparat er ejendommeligt ved, at det omfatter en stabil blanding med fra ca. 30 til ca. 50 volumenprocent af en vandfri ethylether i en farmaceutisk acceptabel naturlig oliebærer, hvorfra de fleste af de frie fedtsyrer er fjernet, hvilkenIn accordance with the invention, there is provided a topical composition for treating an epidermal region of a human infected with herpes simplex virus, which composition is characterized in that it comprises a stable mixture of from ca. 30 to approx. 50% by volume of anhydrous ethyl ether in a pharmaceutically acceptable natural oil carrier, from which most of the free fatty acids are removed, which

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3 blanding har et kogepunkt på mindst ca. 38eC.3 mixture has a boiling point of at least approx. 38eC.

Fortrinsvis tilføres det inficerede område varme kort tid efter, at det topiske præparat er påført, for eksempel tilføres der varme i en periode på mellem 3 og 15 minutter ca. 3 minutter efter, at det 5 topiske præparat er påført.Preferably, the infected area is heat applied shortly after the topical composition is applied, for example, heat is applied for a period of between 3 and 15 minutes approx. 3 minutes after the 5 topical preparation is applied.

I overensstemmelse med den foreliggende opfindelse har det vist sig, at et topisk præparat, som indeholder en blanding af vandfri ethyl ether og en kokosnødoliebærer, hvorfra de fleste frie fedtsyrer er fjernet, er effektivt i behandlingen af epidermisområder, som er 10 inficeret med herpes simplex virus.In accordance with the present invention, it has been found that a topical composition containing a mixture of anhydrous ethyl ether and a coconut oil carrier from which most free fatty acids are removed is effective in the treatment of epidermal areas infected with herpes simplex. virus.

Det har været kendt i nogen tid, at ethyl ether er meget nyttig til behandlingen af forkølelsessår i et epidermisområde inficeret med herpes simplex virus. I denne henseende skader eller fjerner etheren den virale kappe, hvorved infektiviteten reduceres. Ether, især ethylether, 15 er imidlertid meget ustabil og har et meget lavt kogepunkt. I overensstemmelse hermed må man være meget omhyggelig med påføringen af ethylether, og førhen er dette kun sket i et kontrolleret miljø så som i et hospitalsambulatorium eller hos en praktiserende læge. Desuden fordamper ethylether hurtigt, og som resultat heraf trænger det ikke dybt ned i 20 det inficerede område.It has been known for some time that ethyl ether is very useful for the treatment of cold sores in an epidermal area infected with herpes simplex virus. In this regard, the ether damages or removes the viral sheath, thereby reducing infectivity. However, ether, especially ethyl ether, is very unstable and has a very low boiling point. Accordingly, care must be taken with the application of ethyl ether, and in the past this has only been done in a controlled environment such as in a hospital ambulatory or a GP. Furthermore, ethyl ether evaporates rapidly and as a result does not penetrate deep into the infected area.

I betragtning af ethers hurtige fordampning er det blevet foreslået i US-patentskrift nr. 4.020.183 at påføre det inficerede område en etherbunden forbindelse i en ikke-irriterende bærer så som en lotion eller olie. På denne måde kan den etherbundne forbindelse i bæreren 25 bibeholdes på det inficerede areal i et signifikant tidsrum til, at den etherbundne forbindelse trænger ind. Den etherbundne forbindelse er imidlertid ikke så stærk og effektiv som ethylether til ødelæggelse af den virale kappe.In view of the rapid evaporation of ethers, it has been proposed in U.S. Patent No. 4,020,183 to apply to the infected area an ether-bound compound in a non-irritating carrier such as a lotion or oil. In this way, the ether bound compound in the carrier 25 can be retained on the infected area for a significant period of time for the ether bound compound to penetrate. However, the ether bound compound is not as strong and effective as ethyl ether for destroying the viral sheath.

I overensstemmelse med den foreliggende opfindelse anvendes således 30 vandfri ethylether, der er et stærkt flygtigt kemikalie. Den skal imidlertid kombineres med en bærer, således at den er mere stabil. Vandfri ethylether anvendes på grund af, at den menes at trænge dybere ind end andre ethere eller etherbundne forbindelser med højere kogepunkt. Desuden er ethylether lettere tilgængelige til anvendelse i den vandfri 35 form end andre ethere, så som methylether der har et lavere kogepunkt.Thus, in accordance with the present invention, 30 anhydrous ethyl ether, which is a highly volatile chemical, is used. However, it must be combined with a carrier so that it is more stable. Anhydrous ethyl ether is used because it is believed to penetrate deeper than other ether or ether-bound compounds having a higher boiling point. In addition, ethyl ether is more readily available for use in the anhydrous form than other ethers, such as methyl ether having a lower boiling point.

Vandfri ethylether indeholder praktisk taget intet vand (0,01%). Ved anvendelsen af vandfri ethylether holdes det inficerede areal således så tørt som muligt. I så henseende forekommer fugtighed at være en hindringAnhydrous ethyl ether contains practically no water (0.01%). Thus, when using anhydrous ethyl ether, the infected area is kept as dry as possible. In this regard, moisture seems to be an obstacle

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4 for helingsprocessen af forkølelsessåret i et område inficeret med herpes simplex virus, når dette påføres ether.4 for the healing process of the cold sore in an area infected with herpes simplex virus when applied to ether.

Den vandfri ethylether, der anvendes ifølge den foreliggende opfindelse har følgende American Chemical Society specifikationer: 5The anhydrous ethyl ether used in the present invention has the following American Chemical Society specifications: 5

Butyleret hydroxytoluen (konserveringsmiddel) 0,5-1 ppmButylated hydroxytoluene (preservative) 0.5-1 ppm

Bestemt (C2H5)20 som CC 98,5%Determined (C 2 H 5) as CC 98.5%

Farvestof (APHA) 10Dye (APHA) 10

Densitet (g/ml ved 25*C max.) 0,7079 10 Peroxid (som H202) 0,0001%Density (g / ml at 25 ° C max) 0.7079 Peroxide (as H2O2) 0.0001%

Remanens efter inddampning 0,001%Residue after evaporation 0.001%

Substanser mørknet af H2S04 NogenlundeSubstances darkened by H2S04 Roughly

Alkohol (C2H50H) 0,01% H20 (Karl Fisher metoden) 0,01% 15 Sporurenheder (i ppm):Alcohol (C2H50H) 0.01% H2O (Karl Fisher method) 0.01% Trace units (in ppm):

Syre (som CHgCOOH) 0,5Acid (as CH 2 COOH) 0.5

Kobber 0,1Copper 0.1

Tungmetaller (AgPB) 0,1Heavy metals (AgPB) 0.1

Nikkel (Nj) 0,1 20 I præparatet ifølge den foreliggende opfindelse anvendes fortrinsvis raffineret kokosnødolie, hvori de fleste frie fedtsyrer er fjernet, som bæreren. Selv om andre naturlige olier kunne anvendes, viste det sig, at kokosnødolie var bedst egnet til blanding med den vandfri ethyl-25 ether.Nickel (Nj) 0.1 20 In the composition of the present invention, refined coconut oil, in which most free fatty acids are removed, is preferably used as the carrier. Although other natural oils could be used, it was found that coconut oil was best suited for blending with the anhydrous ethyl ether.

Den raffinerede og blegede eller hydrogenerede kokosnødoliebærer opnås på følgende måde.The refined and bleached or hydrogenated coconut oil carrier is obtained as follows.

Først raffineres kokosnødolie med kaustisk soda (NaOH), hvilken fremgangsmåde også kendes som raffinering af et glycerid. Her nedbrydes 30 den naturlige olie (et glycerid) til glycerolestere og en sæbe, som indeholder de fleste (mindst 95%) af de frie fedtsyrer. Glycerol esteren bibeholdes, og denne fremgangsmåde til fjernelse af de i olien fundne frie fedtsyrer (for eksempel palmitin-, caprin-, olein-, 1 i nol - og linolensyrer) gør bæreren langt mindre irriterende for huden. Olien 35 indeholder nu ikke mere end 7% frie fedtsyrer og fortrinsvis mellem 2,5 og 3,5% frie fedt-syrer. Det menes, at den raffinerede kokosnødoliebærer hjælper med til at hele epidermisområdet omkring forkølelsessåret, hvilket område er blevet tappet for fugtighed ved påføringen af denFirst, coconut oil is refined with caustic soda (NaOH), which is also known as refining a glyceride. Here, the natural oil (a glyceride) is broken down into glycerol esters and a soap containing most (at least 95%) of the free fatty acids. The glycerol ester is retained, and this method of removing the free fatty acids found in the oil (e.g., palmitic, caprin, olein, 1 in zero and linolenic acids) makes the wearer far less irritating to the skin. The oil 35 now contains no more than 7% free fatty acids and preferably between 2.5 and 3.5% free fatty acids. It is believed that the refined coconut oil carrier helps the entire epidermal area around the cold sore, which area has been tapped for moisture when applied to it.

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5 vandfri ethyl ether, ved forsegling af dette epidermisområde mod luft og vand, der kan hindre helingsprocessen.5 anhydrous ethyl ether, by sealing this epidermal area against air and water which may hinder the healing process.

Efter raffineringen foradies glycerolesteren yderligere, den kan for eksempel hydrogeneres, til dannelse af stearinsyre {koldcreme) og 5 det ønskede produkt, raffineret og hydrogeneret kokosnødolie, som er den bærer, der anvendes i blandingen sammen med den vandfri ethyl ether. Det er blevet vist empirisk, at det bedst egnede brydningsindex af hydrogenering for bæreren er 1,4540 ± 0,0002 ved 25T og et iodtal på 4,5 ± 0,5.After refining, the glycerol ester is further added, it can be hydrogenated, for example, to form stearic acid (cold cream) and the desired product, refined and hydrogenated coconut oil, which is the carrier used in the mixture with the anhydrous ethyl ether. It has been shown empirically that the most suitable refractive index of hydrogenation for the support is 1.4540 ± 0.0002 at 25T and an iodine number of 4.5 ± 0.5.

10 Raffinering og hydrogenering af olier er velkendte processer, og måden, hvorpå disse processer udføres, er beskrevet i et værk med titlen "Official and Tentative Methods of the American Oil Chemist's Society" (3. udgave) 1976, udgivet af American Oil Chemist's Society, Champaign, Illinois. I dette værk beskrives teknikker til raffinering af olie i 15 A.O.C.S. Official Method Cc 8d-55 side 1-3, og teknikker til hydrogenering af olie er beskrevet i A.O.C.S. Recommended Practice Ca 17-76 side 1-3.10 Refining and hydrogenation of oils are well known processes, and the manner in which these processes are performed is described in a work entitled "Official and Tentative Methods of the American Oil Chemist's Society" (3rd ed.) 1976, published by the American Oil Chemist's Society , Champaign, Illinois. In this work, oil refining techniques are described in 15 A.O.C.S. Official Method Cc 8d-55 pages 1-3, and oil hydrogenation techniques are described in A.O.C.S. Recommended Practice Approx 17-76 page 1-3.

Denne hydrogeneringsproces menes at forsinke udviklingen af harskhed i olien, et almindeligt problem for oliebaserede forbindelser, og 20 muliggør således en længere lager- og brugstid.This hydrogenation process is believed to delay the development of rancidity in the oil, a common problem for oil-based compounds, thus enabling a longer storage and service life.

Raffineret og bl eget eller hydrogeneret kokosnødolie, der har et iodtal på 4,5 ± 0,5, der ikke indeholder mere end 7% frie fedtsyrer (FFA som olein), og med et brydningsindeks på 1,4540 ± 0,0002 ved 25*C, kan fås fra: 25 CPC International International Plaza P.0. Box 500Refined and blended or hydrogenated or hydrogenated coconut oil having an iodine value of 4,5 ± 0,5 containing not more than 7% free fatty acids (FFA as olein) and having a refractive index of 1.4540 ± 0.0002 at 25 * C, available from: 25 CPC International International Plaza P.0. Box 500

Englewood Cliffs, New Jersey, 30 fra dets datterselskabEnglewood Cliffs, New Jersey, 30 from its subsidiary

Best Foods CPC International 35 2841 S. KilbourneBest Foods CPC International 35 2841 S. Kilbourne

Chicago, Illinois og fraChicago, Illinois and from

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66

Capital City Produts 1200 Route 46 W. New York, New Jersey 5 En foretrukken delvis hærdet raffineret og bl eget (eller hydro generet) kokosnødolie har følgende materialespecifikationer:Capital City Product's 1200 Route 46 W. New York, New Jersey 5 A preferred partially cured refined and blended (or hydro-generated) coconut oil has the following material specifications:

Farvestof (Lovibond) Max. 4,0 rød F.F.A. (som olein) Max. 7,0% 10 M.I.U. (fugtighedsinert) Max. 1,0%Dye (Lovibond) Max. 4.0 Red F.F.A. (like olein) Max. 7.0% 10 M.I.U. (moisture inert) Max. 1.0%

Forsæbningstal Min. 254Saponification figures Min. 254

Polyumættede syrer* Max. 0,40% lodtal 4,5 ± 0,5Polyunsaturated acids * Max. 0.40% Vertical 4.5 ± 0.5

Lugt Sædvanlige karakteristiske lugt 15 Brydningsindex 1,4540 ± 0,0002 * Bestemmes ved hjælp af A.O.C.S. Method Cd 7-58.Odor Usual characteristic odor Refractive index 1.4540 ± 0.0002 * Determined by A.O.C.S. Method Cd 7-58.

(F.F.A. = frie fedtsyrer og M.I.U. = fugtighedsinert ikke-forsæbende).(F.F.A. = free fatty acids and M.I.U. = moisture inert non-soaping).

20 Ved raffineringen af kokosnødolien fjernes de frie fedtsyrer, d.v.s. de frie fedtsyrer omdannes til sæbe, som udfælder og fjernes som bundfald, mens glycerolestere af andre fedtsyrer bibeholdes, f.eks. glycerol esterne Cg til Cjg. Hydrogeneringen omdanner således de ustabile glycerol estere, for eksempel olein (ustabil) til stearin (stabil).In refining the coconut oil, the free fatty acids, i.e. the free fatty acids are converted to soap which precipitates and is removed as a precipitate while retaining glycerol esters of other fatty acids, e.g. the glycerol esters Cg to Cjg. The hydrogenation thus converts the unstable glycerol esters, for example olein (unstable) to stearin (stable).

25 Kokosnødnolie er en blanding af estere af fedtsyrer med et lige antal carbonatomer fra Cg til Cjgj. Mængderne af Cg og CgQ er nul. Fordelingen er som følger:Coconut oil is a mixture of esters of fatty acids with an equal number of carbon atoms from Cg to Cjgj. The quantities of Cg and CgQ are zero. The breakdown is as follows:

Fedtsyre %_ 30 Cg (capron) NulFatty acid% _ 30 Cg (capron) Zero

Cg (capryl) 6 ± 1Cg (capryl) 6 ± 1

Cjq (caprin) 7 ± 1Cjq (caprin) 7 ± 1

Cjg (laurin) 48,5 ± 1,5 (myristin) 19,0 ± 1,0 35 Cjg (palmetin) 8,75 ± 0,75Cjg (laurine) 48.5 ± 1.5 (myristine) 19.0 ± 1.0 Cjg (palmetin) 8.75 ± 0.75

Cjg (stearin) 5,25 ± 0,75 ^18-1 3,00 ± 0,50 7Cjg (stearin) 5.25 ± 0.75 ^ 18-1 3.00 ± 0.50 7

De frie fedtsyrer i kokosnødolien vil forsæbe under visse betingelser under raffineringen af den rå kokosnødolie, mens de andre komponenter ikke vil.The free fatty acids in the coconut oil will sap under certain conditions during the refining of the raw coconut oil, while the other components will not.

I for eksempel én raffineringsfremgangsmåde anbringes 500 g rå 5 kokosnødolie i et vandbad med en mekanisk omrører ved en temperatur mellem 30 og 35eC og ved 250 opm. Dernæst tilsættes en mængde af 20# Baume NaOH for effektivt at forsæbe de frie fedtsyrer, for eksempel CJ7H33COOH (oleinsyre + NaOH = CjyH^COONa + HgO). Oleinsyrens molekylvægt er 282,4 og natriumhydroxids molekylvægt er 40.For example, in one refining process, 500 g of crude 5 coconut oil is placed in a water bath with a mechanical stirrer at a temperature between 30 and 35 ° C and at 250 rpm. Next, an amount of 20 # Baume NaOH is added to effectively saponify the free fatty acids, for example CJ7H33COOH (oleic acid + NaOH = CjyH2 COONa + HgO). The molecular weight of the oleic acid is 282.4 and the molecular weight of sodium hydroxide is 40.

10 Efter at mængden af NaOH er blevet bestemt ved konventionelle beregningsmetoder, sættes det til olien, der herefter omrøres i 5 minutter. Dernæst nedsættes hastigheden til 70 opm og vandbadets temperatur forøges hurtigt til 50-53eC. Der omrøres i 10 til 15 minutter eller mere, indtil bundfaldet (bundsæben) er klar til fjernelse. Når 15 olien er relativt klar, fjernes den raffinerede olie.After the amount of NaOH has been determined by conventional calculation methods, it is added to the oil, which is then stirred for 5 minutes. The speed is then reduced to 70 rpm and the temperature of the water bath is rapidly increased to 50-53 ° C. Stir for 10 to 15 minutes or more until the precipitate (bottom soap) is ready for removal. When the oil is relatively clear, the refined oil is removed.

Ved blegning af den raffinerede kokosnødolie anvendes et 60 mesh (0,25 mm) filter, blegejord som i American Oil Chemists Societys standarder, filterpapir (Sargent Welch Grade S 32915-J eller tilsvarende) og rullet bomuld. Filtret opstilles med tynde lag rullet bomuld, og 300 g 20 raffineret olie får lov at filtrere ned i en rustfri stålskål, der herefter placeres under en mekanisk omrører. Herefter tilsættes 9 g blegejord, og der omrøres ved en temperatur på 100 til 110eC. Omrøringshastigheden er stor nok til at holde bl egepulveret i suspension i 5 minutter. Dernæst filtreres opløsningen gennem en ståltragt med filter-25 papir, og filtratet af raffineret og bl eget kokosnødolie opsamles i et bægergi as.When bleaching the refined coconut oil, use a 60 mesh (0.25 mm) filter, bleaching soil as per American Oil Chemists Society's standards, filter paper (Sargent Welch Grade S 32915-J or equivalent) and rolled cotton. The filter is set up with thin layers of rolled cotton, and 300 g of 20 refined oil is allowed to filter into a stainless steel bowl, which is then placed under a mechanical stirrer. Then 9 g of pale earth is added and stirred at a temperature of 100 to 110 ° C. The stirring rate is large enough to hold the bleach powder in suspension for 5 minutes. Next, the solution is filtered through a filter funnel with filter paper and the filtrate of refined and blended coconut oil is collected in a beaker.

Blandingen af vandfri ethyl ether og den hydrolyserede og hydrogenerede kokosnødolie eller den raffinerede og blegede kokosnødolie blandes i et forhold fra 1:2 til 1:1, idet vandfri ethyl ether pr. volumen 30 til kokosnødolie pr. volumen i et forhold på 2:3 foretrækkes.The mixture of anhydrous ethyl ether and the hydrolyzed and hydrogenated coconut oil or the refined and bleached coconut oil is mixed in a ratio of 1: 2 to 1: 1, with anhydrous ethyl ether per liter. volume 30 to coconut oil per volume in a ratio of 2: 3 is preferred.

Det fremgik af talrige tests, at ved kombination af kokosnødolien med den vandfri ethyl ether i et forhold på 3:2 efter volumen, hvorved der dannes en overmættet blanding, hæves blandingens normale kogepunkt til ca. 48*C. Denne numeriske forholdskombination af olie og ether 35 iagttoges også at forårsage mindst skade, d.v.s. nekrose, på det levedygtige væv, der omgiver herpeslæsionen, mens det stadig tilvejebringer et meget effektivt middel til destruktion af den virale kappe.Numerous tests have shown that by combining the coconut oil with the anhydrous ethyl ether at a 3: 2 by volume ratio to form a supersaturated mixture, the normal boiling point of the mixture is raised to approx. 48 * C. This numerical ratio combination of oil and ether 35 was also observed to cause the least amount of damage, i.e. necrosis, on the viable tissue surrounding the herpes lesion, while still providing a very effective means of destroying the viral sheath.

Blandingen anvendes som topisk præparat på det inficerede områdeThe mixture is used as a topical preparation in the infected area

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8 eller områder i en mængde, som er tilstrækkelig til at dække det inficerede areal eller arealer én gang om dagen i et tidsrum på fra 1 uge op til 90 dage, om nødvendigt. Empiriske målinger indikerer, at den 3 anvendte mængde er ca. 1 cm for ca. hver 1/4 kvadrattomme (US) (0,4 2 5 cm ) inficeret overfladeareal. Mere specifikt anvendes præparatet dagligt, indtil forkølelsessåret i det inficerede område ikke længere er synligt.8 or areas in an amount sufficient to cover the infected area or areas once a day for a period of from 1 week up to 90 days, if necessary. Empirical measurements indicate that the amount used is approx. 1 cm for approx. every 1/4 square inch (US) (0.4 2.5 cm) of infected surface area. More specifically, the preparation is used daily until the cold sore in the infected area is no longer visible.

Fortrinsvis tilføres det inficerede område også varme, og det er blevet observeret, at den tilførte varme synes at forbedre og medvirke 10 til helingsprocessen, d.v.s. til forkølelsessårenes forsvinden.Preferably, the infected area is also supplied with heat, and it has been observed that the heat applied appears to improve and contribute to the healing process, i.e. to the disappearance of the cold sores.

To typer varme er blevet anvendt med gode resultater. Den ene er stråling, infrarød eller tør varme, og den anden er våd varme påført med et varmt, vådt håndklæde.Two types of heat have been used with good results. One is radiation, infrared or dry heat, and the other is wet heat applied with a warm, wet towel.

Strålingen, infrarød, varme tilføres ved så høj en temperatur som 15 patienten kan udholde i en periode på 15 til 20 minutter om morgenen efter at præparatet er blevet påført. Den infrarøde kilde placeres ca.The radiation, infrared, heat is applied at as high a temperature as the patient can endure for a period of 15 to 20 minutes in the morning after the preparation has been applied. The infrared source is placed approx.

40 cm eller mere fra det inficerede område på patientens ansigt, idet der anbringes en maske over de tilstødende ansigtsområder, særligt over øjnene for at beskytte disse. Strålingsvarmen synes at hjælpe med til 20 tørring af læsionerne og viste sig at være meget effektiv til tørring af multiple udbrud.40 cm or more from the infected area on the patient's face, applying a mask over the adjacent facial areas, especially over the eyes to protect them. Radiation heat seems to help with 20 drying of the lesions and proved to be very effective for drying multiple outbreaks.

Det menes også, at anvendelsen af varme forøger blodtilførslen til det inficerede område og forøger oxygeneringen af vævet i dette område, for således yderligere at bistå helingen. Desuden menes forøget blod-25 strøm forårsaget af anvendelse af varme at fremme en hurtigere fjernelse af det nedbrudte materiale, som efterlades, når læsionen ødelægges.It is also believed that the use of heat increases the blood supply to the infected area and increases the oxygenation of the tissue in that area, thus further assisting the healing. In addition, increased blood flow caused by the use of heat is believed to promote a faster removal of the degraded material which is left behind when the lesion is destroyed.

Som et alternativ til infrarød varme kan våd varme i form af varme, våde håndklæder anvendes på de inficerede områder ved en så høj temperatur som patienten kan udholde i en periode på 15 til 20 minutter hver 30 morgen og hver aften, idet det topiske præparat påføres én gang dagligt om aftenen.As an alternative to infrared heat, wet heat in the form of warm, wet towels can be applied to the infected areas at as high a temperature as the patient can endure for a period of 15 to 20 minutes every 30 mornings and every evening, applying the topical preparation. once daily in the evening.

For individer, som er udsat for multiple infektioner med regelmæssige intervaller, påføres det topiske præparat tre gange dagligt i de første fem dage, og derefter påføres det topiske præparat tre gange 35 dagligt i de næste fem dage, idet hver påføring efterfølges af påføring af et varmt, vådt håndklæde (så varmt som individet kan udholde) i 3 til 20 minutter tre gange dagligt.For individuals who are exposed to multiple infections at regular intervals, the topical composition is applied three times daily for the first five days, and then the topical preparation is applied three times 35 daily for the next five days, each application being followed by application of a warm, wet towel (as hot as the individual can endure) for 3 to 20 minutes three times daily.

I én fremgangsmåde til behandling påføres ca. 2 cm af det topiske 9 υκ itKn»a a præparat det inficerede areal rundt om for eksempel læberne. Efter tre minutter lægges et vådt håndklæde, så varmt som patienten kan udholde, på området i ca. tre minutter.In one method of treatment, approx. 2 cm of the topical 9 υκ itKn »a a preparation the infected area around, for example, the lips. After three minutes, a wet towel, as warm as the patient can endure, is placed on the area for approx. three minutes.

Det menes, at uden varme trænger etheren så dybt ned i det infice-5 rede areal som muligt i løbet af ca. 3 minutter. Herefter menes det, at varmen fra det våde håndklæde får etheren, der er trængt ind, til at fordampe, hvorved det drives eller bevæger sig op igennem trigeminus-kanalen og dræber virus, der gemmer sig heri på et hvilestadie, og som senere bliver aktive og forårsager periodisk tilbagevendende infek-10 tioner. Igen menes det, at ca. tre minutter er tilstrækkelig til at holde dampene bevægelige i kanalen med et tilstrækkeligt tryk og volumen til ødelæggelse af virus.It is believed that without heat, the ether penetrates as deep into the infected area as possible over the course of approx. 3 minutes. After that, it is believed that the heat from the wet towel causes the ether that has penetrated to evaporate, thereby propelling or moving up through the trigeminal tract and killing viruses which hibernate there at a resting state and which later become active and periodically recurring infections. Again, it is believed that approx. three minutes is sufficient to keep the vapors moving in the duct with sufficient pressure and volume to destroy the virus.

Empiriske studier viser, at én fremgangsmåde til behandling består i at påføre det topiske præparat mindst én gang (fortrinsvis to gange) 15 dagligt i tre dage. Herefter påføres på den tredie dag, selv om forkølelsessårene synes at være afhjulpet, præparatet og varmen som beskrevet ovenfor tre gange dagligt i mindst tre dage. Det menes, at medikamentet efter dette tidsrum har vundet kampen og dræbt virusen på infektionsstedet, og at kroppens immunsystem kan overtage kampen og tvinge virusen 20 til flugt via trigeminuskanal en.Empirical studies show that one method of treatment consists of applying the topical composition at least once (preferably twice) 15 daily for three days. Thereafter, on the third day, although the cold sores appear to have been remedied, the preparation and heat as described above are applied three times daily for at least three days. It is believed that after this period, the drug has won the battle and killed the virus at the site of infection, and that the body's immune system can take over the fight and force the virus 20 to escape via the trigeminal tract.

Eksemplerexamples

To individer, der i gennemsnit havde haft ét forkølelsessår pr. år i de 2 år, som gik forud for behandlingen, behandledes med et topisk 25 præparat ifølge opfindelsen, der indeholdt 60 volumenprocent kokosnødolie, hvorfra de fleste af de fede fedtsyrer var fjernet, og 40 volumenprocent vandfri ethylether, der påførtes det inficerede område én gang dagligt i 7 dage samtidig med, at der tilførtes stråling, infrarød varme, én gang dagligt om morgenen efter påføring af det topiske præpa-30 rat. Ingen genkomst af forkølelsessår observeredes i et tidsrum på 7 år efter denne behandling.Two individuals who had on average one cold sore per day. Years in the 2 years preceding treatment were treated with a topical 25 composition of the invention containing 60% by volume of coconut oil from which most of the fatty fatty acids were removed and 40% by volume of anhydrous ethyl ether applied to the infected area once daily for 7 days at the same time as radiation, infrared heat was applied, once daily in the morning after application of the topical preparation. No recurrence of cold sores was observed for a period of 7 years after this treatment.

Otte individer, der i gennemsnit havde fire forkølelsessår pr. år i de ti år, som gik forud for behandlingen, behandledes med et topisk præparat ifølge den foreliggende opfindelse, der indeholdt 60 volumen-35 procent kokosnødolie, hvorfra de fleste af fedtsyrerne var fjernet, og 40 volumenprocent vandfri ethyl ether, hvilket præparat påførtes det inficerede areal én gang dagligt i 90 dage samtidig med at våd varme tilførtes ved hjælp af varme, våde håndklæder to gange dagligt i 90Eight individuals who had an average of four cold sores per day. for the ten years preceding the treatment, was treated with a topical composition of the present invention containing 60% -35% coconut oil from which most of the fatty acids were removed and 40% by volume of anhydrous ethyl ether applied to it. infected area once daily for 90 days while applying wet heat using warm, wet towels twice daily for 90 days.

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10 dage. Efter denne behandling observeredes ingen genkomst af forkølelsessår i en periode på 2¼ år efter behandlingen. Graden af infektion for disse individer var således, at gennemsnitlig to af fire tilsynekomster af forkølelsessår var multiple læsioner.10 days. After this treatment, no recurrence of cold sores was observed for a period of 2¼ years after treatment. The degree of infection for these individuals was that on average two out of four appearances of cold sores were multiple lesions.

5 Endnu fire individer, der i gennemsnit havde haft fem forkølelses sår pr. år i de ti år, der gik forud for behandlingen, behandledes med et topisk præparat ifølge den foreliggende opfindelse, der bestod af 60 volumenprocent kokosnødolie, hvorfra de fleste fedtsyrer var fjernet, og 40 volumenprocent vandfri methyl ether, hvilket præparat påførtes det 10 inficerede område én gang dagligt i 90 dage, og samtidig hermed tilførtes våd varme ved hjælp af varme, våde håndklæder to gange om dagen i 90 dage. Graden af infektion for disse individer var således, at gennemsnitlig fire ud af fem forekomster af forkølelsessår var multiple læsioner. Ingen genkomst af forkølelsessår observeredes for disse indi-15 vider i en periode på to år efter behandlingen.5 Another four individuals who had an average of five cold sores per day. Years in the ten years preceding the treatment were treated with a topical composition of the present invention consisting of 60% by volume of coconut oil from which most fatty acids had been removed and 40% by volume of anhydrous methyl ether applied to the 10 infected area. once daily for 90 days, and at the same time wet heat was applied by means of warm, wet towels twice a day for 90 days. The degree of infection for these individuals was that on average, four out of five cold sores were multiple lesions. No recurrence of cold sores was observed for these individuals for a period of two years after treatment.

Andre ti individer, der havde haft gennemsnitlig to forkølelsessår pr. år i de ti år, som gik forud for behandlingen, behandledes med et topisk præparat ifølge den foreligende opfindelse, der indeholdt 60 volumenprocent kokosnødolie, hvorfra de fleste fedtsyrer var fjernet, og 20 40 volumenprocent vandfri ethyl ether, hvilket præparat påførtes det inficerede område én gang dagligt i 20 dage sammen med anvendelsen af våd varme ved hjælp af varme, våde håndklæder to gange dagligt i 20 dage. Efter denne behandling observeredes ingen genkomst af forkølelsessår i to år efter behandlingen.Another ten individuals who had had an average of two cold sores per day. for the ten years preceding the treatment, was treated with a topical composition of the present invention containing 60% by volume of coconut oil from which most fatty acids were removed and 20% by volume of anhydrous ethyl ether applied to the infected area one once daily for 20 days along with the application of wet heat using warm, wet towels twice daily for 20 days. After this treatment, no recurrence of cold sores was observed for two years after treatment.

25 Det vil kunne forstås, at det topiske præparat ifølge opfindelsen har gjort en sikker afgivelse af ethylether til et epidermisområde, som er inficeret med herpes simplex virus, mulig. I så henseende blandes vandfri ethylether i den raffinerede og blegede kokosnødoliebærer, som beskrevet ovenfor, således at den vandfri ethylethers varmeinstabilitet 30 modvirkes af kokosnødoliebærerens høje kogepunkt. På denne måde forøges kogepunktet for den samlede emulsion fra det normale kogepunkt for ethylether på 34,6*C op til ca. 54,4eC. Denne forøgelse af kogepunktet for blandingen gør det muligt at oplagre ethyletheren i blandingen lettere og mere sikkert, hvorved den kan anvendes uden for det kontrol-35 lerede miljø i et hospitalsambulatorium eller hos en praktiserende læge.It will be appreciated that the topical composition of the invention has made possible the safe delivery of ethyl ether to an epidermal area infected with herpes simplex virus. In this regard, anhydrous ethyl ether is blended into the refined and bleached coconut oil carrier, as described above, so that the thermal instability of the anhydrous ethyl ether 30 is counteracted by the high boiling point of the coconut oil carrier. In this way, the boiling point of the total emulsion is increased from the normal boiling point of ethyl ether of 34.6 ° C up to approx. 54,4eC. This increase of the boiling point of the mixture makes it possible to store the ethyl ether in the mixture more easily and more securely, whereby it can be used outside the controlled environment in a hospital ambulatory or by a practitioner.

Det vil også kunne forstås, at ved at tilføre det inficerede område varme sammen med påføringen af det topiske præparat fremskyndes og forøges helingen af forkølelsessårene. Som angivet ovenfor menes det, at 11It will also be appreciated that by applying heat to the infected area together with the application of the topical composition, healing of the cold sores is accelerated and enhanced. As stated above, it is believed that 11

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dette skyldes den forøgede blodstrøm til det inficerede område som resultat af den dertil tilførte varme.this is due to the increased blood flow to the infected area as a result of the heat supplied.

Et andet vigtigt træk ved den foreliggende opfindelse er, at der, når der anvendes mindst 30 volumenprocent vandfri ethylether i en raffi -5 neret og bleget kokosnødoliebærer i modsætning til en etherbundet forbindelse, fås et stærkere middel til behandlingen af herpes simplex virus, hvorved der tilvejebringes et mere effektiv behandling. I så henseende er den vandfri ethylether mere effektiv end den etherbundne forbindelse til ødelæggelsen af herpes simplex virus' vi rale kappe, 10 hvorved der tilvejebringes en mere effektiv behandling. I så henseende er den vandfri ethylether mere effektiv end den etherbundne forbindelse til ødelæggelse af den virale kappe, og emulsionen muliggør påføringen af et tilstrækkeligt volumen ethylether til det inficerede område. Ved anvendelse af vandfri ethylether placeres der desuden praktisk talt 15 intet vand i kontakt med det inficerede område, når etheren påføres, hvilket yderligere hjælper på helingsprocessen.Another important feature of the present invention is that when at least 30% by volume of anhydrous ethyl ether is used in a refined and bleached coconut oil carrier as opposed to an ether bound compound, a stronger agent for the treatment of herpes simplex virus is obtained, thereby providing more effective treatment is provided. In this regard, the anhydrous ethyl ether is more effective than the ether-bound compound for the destruction of the herpes simplex virus sheath, thereby providing a more effective treatment. In this regard, the anhydrous ethyl ether is more effective than the ether bound compound for destroying the viral sheath and the emulsion enables the application of a sufficient volume of ethyl ether to the infected area. In addition, using anhydrous ethyl ether, virtually no water is placed in contact with the infected area when the ether is applied, which further aids in the healing process.

En anden fordel ved det topiske præparat ifølge den foreliggende opfindelse er anvendelsen af raffineret og bleget kokosnødolie, hvorfra mange af de hudirriterende frie fedtsyrer er fjernet. Den raffinerede og 20 blegede kokosnødoliebærer tjener desuden til beskyttelse af det inficerede område under behandling mod luft og vand, der ofte virker hindrende for helingsprocessen.Another advantage of the topical composition of the present invention is the use of refined and bleached coconut oil from which many of the skin irritating free fatty acids are removed. The refined and 20 bleached coconut oil carrier additionally serves to protect the infected area during treatment against air and water, which often impedes the healing process.

Det fremgår af den foregående beskrivelse, at det topiske præparat til behandling af herpes simplex virus ifølge den foreliggende opfin-25 delse har en række fordele, hvoraf nogle er beskrevet ovenfor. For eksempel er det blevet observeret, at ved behandling af forkølelsessårsvirus og ved udnyttelse af det topiske præparat ifølge den foreliggende opfindelse formindskes lokal genkomst af forkøl elesessår stærkt, hvis ikke de helt igennem elimineres, og sådan forebyggelse af 30 genkomst er et stort ønske, når det gælder behandlingen af herpes simplex virus infektivitet.It will be apparent from the foregoing description that the topical composition for the treatment of herpes simplex virus of the present invention has a number of advantages, some of which are described above. For example, it has been observed that in treating cold sore virus and by utilizing the topical composition of the present invention, local recurrence of cold sore ulcers is greatly diminished if not completely eliminated, and such prevention of recurrence is a great desire when It applies to the treatment of herpes simplex virus infectivity.

De empiriske tests har deuden vist, at det topiske præparat er effektivt til behandling in vivo af herpes 1, herpes 2.In addition, the empirical tests have shown that the topical preparation is effective for the in vivo treatment of herpes 1, herpes 2.

3535

Claims

1. Topical composition for treating an epidermal area of a human infected with herpes simplex virus, characterized in that it contains a stable mixture of from ca. 30 to approx. 50 volume 5% anhydrous ethyl ether in a pharmaceutically acceptable natural oil carrier from which most of the free fatty acids have been removed, the mixture having a boiling point of at least about 50 38 ° C.

2. Topical composition according to claim 1, characterized in that the natural oil is refined so that it does not contain more than 7% free 10 fatty acids.

3. Topical composition according to claim 1 or 2, characterized in that the natural oil is hydrogenated.

4. Topical composition according to claim 3, characterized in that the refractive index of the hydrogenated oil is 1.4540 ± 0.0002 at 25 ° C.

5. Topical composition according to claim 2 or 3, characterized in that the iodine number for the hydrogenated oil is 4.5 ± 0.5.

6. Topical composition according to any one of claims 1 to 5, characterized in that the oil is refined and of its own oil.

7. A topical composition according to any one of claims 1 to 6, characterized in that it has a boiling point of approx. 48eC.

8. Topical composition according to any one of claims 1 to 7, characterized in that the numerical ratio of the volume of the natural oil to the volume of the anhydrous ethyl ether is 3: 2.

9. Topical composition according to any one of claims 1 to 8, characterized in that the mixture is supersaturated with respect to the ethyl ether.

Topical composition according to any one of claims 1 to 9, characterized in that the oil is refined coconut oil. 1 35