CA2056392A1 - Topical treatment of herpesvirus hominis - Google Patents
Topical treatment of herpesvirus hominisInfo
- Publication number
- CA2056392A1 CA2056392A1 CA002056392A CA2056392A CA2056392A1 CA 2056392 A1 CA2056392 A1 CA 2056392A1 CA 002056392 A CA002056392 A CA 002056392A CA 2056392 A CA2056392 A CA 2056392A CA 2056392 A1 CA2056392 A1 CA 2056392A1
- Authority
- CA
- Canada
- Prior art keywords
- hyaluronic acid
- salt form
- herpesvirus hominis
- epithelia
- hominis
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
A method of retarding and reversing the effects of herpesvirus hominis comprises topically applying to human epithelia in an area affected by herpesvirus hominis, hyaluronic acid or its biocompatible salt form having a viscosity greater than about 0.4 Pascal seconds in an amount effective to retard and reverse the effects of herpesvirus hominis.
Description
WO90/1409S PCT/US90/~943 Z~S~i3~
~ .,.
TOPICAL TREAT~ENT OF ~ERPB~VIRUB ~OMINIS
.
~lal~ o~ th~ ~nvention The present invention relates to methods o~
retarding or reversing the ef~ects of herpesvirus hominis using high molecular weight hyaluronic acid or its biocompatible salt form.
10_~k~xoun~ o~ th~ ~nvantion ~ lerpes or herpc~ ~implex i~ a r~urrcnt viral in~ection charact~riznd by the app~ar~n~e on the epithelium, specificall~ skin or mucous m~mbrane, o~ simple or multiple clusters of ~mall vesicles or lesions ~illed with a clear fluid on slightly raised inflammatory bases. The infective agent in humans is the relatively large herpes simplex ~irus tHSV) known as herpesvirus hominis.
There are two HSV strains: HSV-l or Type I -herpesvirus hominis and HSV-2 or Type II
; herpesvirus hominis. HSV-l typically ca~ses herpes labalis and keratitis, more commonly called ~eve~
:
~ .
' , . ..
W090JI409s ;~ - PCT/US90/02~43 2~5639;. - 2 -blisters or cold sores. HSV-2 typically cau~es genital herpes. ;
After initial exposure to the virus and the onset of cutaneous lesions, the HSV remains latent in the s~in or nerve ganglla. Recurrent eruptions may be precipltat~d by various ~orms o~ physiaal and/or e~otlonal Btress~ ~tQr a short prodromal period o~ tingling discomfort or itching, small vesicles appear on an erythematous base. Single clusters may occur or coalesce to rOrm painrul vesiclcs. The~e ves~oles parsi~t ~or a ~ew day~
then begin to dry, ~orming a thinl y~llowi~h c~U~t.
Healing begin~ in ~v~n to ton d~ly~ artar on~t nnd iS gen~rally complets :ln twonty-on~ ~2~) daya.
Genital herpes ~s an in~ection which may be sexually tr~nsmitted and may be transmitted by women to an u~born chil~ in utero.
There is presently no cure for herpesvirus hominis. Analgesics may be administered to alleviate irritation. However, analgesic administration generally does not help alleviate the outward symptoms of herpesvirus hominis and does not inhi~it or prevent the onset of cutaneous lesions.
. ,: ., . i WOsO/1409~ 2C5~92 PCT~US90/02943 h ~t~3~." t Generally, "hyaluronic acid~ ~HA) designates an acidic polysaccharide having a molecular weight in a range of about 50,000 to about 8 million Daltons~ depending on its source, method of preparation and method of meiasurement or method of determination. ~he molecular weight and concentration in ~olutlon oS hyaluronic acid generally corresponds directly with its viscosity, with a hiigher ~olecular weight generally resulting in a higher viscosity.
Hyaluronic acid generally comprisaiq equimolar parti~ of d-glucouronic acid and N~ -acctyl-D-gluco~amin~ and iB i~i na~uri~lly OGCUrrlllg compound prei~nt on c~llulo~c ~ur~aoe~, in ~hc basic extracellular sub~tanaes o~ ~he connective tissues o~ vertebrates, in synovial fluid, in pathologic joints, in group A and C hemolytic streptococci, in Wharton's jelly, in the umbilical cord, in rooster combs, in shark cartilage and in 20 pig snoutis. ~
When dissolved in solution, hyaluronic acid ~-forms random coils which interact with other polysaccharides and achieves an unusually large hydrodynamic volume. Such interaction helps a~count for its viscous nature in solution. For ' `
, W090~14095 '~ PCT/US90/02943 2~5~39;~ ~
~ .,.
TOPICAL TREAT~ENT OF ~ERPB~VIRUB ~OMINIS
.
~lal~ o~ th~ ~nvention The present invention relates to methods o~
retarding or reversing the ef~ects of herpesvirus hominis using high molecular weight hyaluronic acid or its biocompatible salt form.
10_~k~xoun~ o~ th~ ~nvantion ~ lerpes or herpc~ ~implex i~ a r~urrcnt viral in~ection charact~riznd by the app~ar~n~e on the epithelium, specificall~ skin or mucous m~mbrane, o~ simple or multiple clusters of ~mall vesicles or lesions ~illed with a clear fluid on slightly raised inflammatory bases. The infective agent in humans is the relatively large herpes simplex ~irus tHSV) known as herpesvirus hominis.
There are two HSV strains: HSV-l or Type I -herpesvirus hominis and HSV-2 or Type II
; herpesvirus hominis. HSV-l typically ca~ses herpes labalis and keratitis, more commonly called ~eve~
:
~ .
' , . ..
W090JI409s ;~ - PCT/US90/02~43 2~5639;. - 2 -blisters or cold sores. HSV-2 typically cau~es genital herpes. ;
After initial exposure to the virus and the onset of cutaneous lesions, the HSV remains latent in the s~in or nerve ganglla. Recurrent eruptions may be precipltat~d by various ~orms o~ physiaal and/or e~otlonal Btress~ ~tQr a short prodromal period o~ tingling discomfort or itching, small vesicles appear on an erythematous base. Single clusters may occur or coalesce to rOrm painrul vesiclcs. The~e ves~oles parsi~t ~or a ~ew day~
then begin to dry, ~orming a thinl y~llowi~h c~U~t.
Healing begin~ in ~v~n to ton d~ly~ artar on~t nnd iS gen~rally complets :ln twonty-on~ ~2~) daya.
Genital herpes ~s an in~ection which may be sexually tr~nsmitted and may be transmitted by women to an u~born chil~ in utero.
There is presently no cure for herpesvirus hominis. Analgesics may be administered to alleviate irritation. However, analgesic administration generally does not help alleviate the outward symptoms of herpesvirus hominis and does not inhi~it or prevent the onset of cutaneous lesions.
. ,: ., . i WOsO/1409~ 2C5~92 PCT~US90/02943 h ~t~3~." t Generally, "hyaluronic acid~ ~HA) designates an acidic polysaccharide having a molecular weight in a range of about 50,000 to about 8 million Daltons~ depending on its source, method of preparation and method of meiasurement or method of determination. ~he molecular weight and concentration in ~olutlon oS hyaluronic acid generally corresponds directly with its viscosity, with a hiigher ~olecular weight generally resulting in a higher viscosity.
Hyaluronic acid generally comprisaiq equimolar parti~ of d-glucouronic acid and N~ -acctyl-D-gluco~amin~ and iB i~i na~uri~lly OGCUrrlllg compound prei~nt on c~llulo~c ~ur~aoe~, in ~hc basic extracellular sub~tanaes o~ ~he connective tissues o~ vertebrates, in synovial fluid, in pathologic joints, in group A and C hemolytic streptococci, in Wharton's jelly, in the umbilical cord, in rooster combs, in shark cartilage and in 20 pig snoutis. ~
When dissolved in solution, hyaluronic acid ~-forms random coils which interact with other polysaccharides and achieves an unusually large hydrodynamic volume. Such interaction helps a~count for its viscous nature in solution. For ' `
, W090~14095 '~ PCT/US90/02943 2~5~39;~ ~
- 4 - ' `' example, a 1% by weight aqueous solution o~ certain -:
hyaluronic acids is about 500,000 times more viscous than water alone. At a 10% by weight - :
' ~:
aqueous solution, hyaluronic acid is so viscous ' that it may be formed into ba'lls. Commercially available a~ueous solution~ generally have vi~cositie~ o~ abou~ 0.~ Pascal soconds ~Pas) to about 108 Pas (see W.E. ~ones, ~'Viscosupplementation in the Joint~ J. Equine Vet. ' ~
10 Sci. 9(2):102-04 (1989)). . '' Hyaluronic ac~d is an inhibitor o~ cell migration, a direct inhibitor o~ luukocykic activity, prev~nts th~ ~orm~tion c~ ~xc~ ibrau~
tiGsue ~nd i~ ~n anti-in~lamma~ory ~g~nt in m~ny uses. Previously ~ndwn u5e8 ~or hyaluronla acid are varie~, ranging rrOm its use to replace vitreous humor in opthalmic surgery, as an anti-inflammatory agent in veterinary medicine and as a vehicle in some cosmetic and pharmaceutical preparations.
8ummary of t~e Invention According to the present invention, a method of retarding and reversing the ef~ects o~
herpesvirus hominis comprises topically applying ~o W O 90/14095 2C~;~i392 P(~r/US9OtO2943 ,~ ' "' ' i - 5 ~ ; 3 human epithelia in an area affected by herpesvirus hominis, hyaluronic acid or its biocompatible salt form having a viscosity greater than about 0.4 Pascal seconds in amount effective to retard and reverse the effect6 of herpesvirus hominis.
Pre~erably, hyaluroni~ acld ~r its biocompatible ~alt ~o nD ha~ a VisC05ity in ~:olutlon c~ about 23 Pas to about 108 Pas and is prescnt in aqueous solution in an amount of about 1o mg/ml.
D~ C De~rlptlon ~ Pre~rra~ Embo~l~ent~
According to th~ pre~nt lnvcntion, the e~P~cts o~ herpQ0v~ru~ homini3 m~y b~ re~ard~d or revers~d by tapi~ally ~pply~ng to human ap~th~lla a~fected by herpesvirus hominis hyaluronic acid or iks biocompatibl~ salt ~o na. E~yaluronic acid or its biocompatible sal~ form should have a viscosity greater than about 0.4 Pas. It will be appreciated by one skill~d in the art in view of this disclosure that viscosity greater than about 0.4 2b Pas helps facilitate inunction or topical application of hyaluronic acid or its biocompatible ; salt form according to the present invention.
According to one embodi~ent o~ the present invention, for example, hyaluronic acid or its ;'' wos~/140~ PCT/US90/02943 . ,.. ~.. , ~ ' ' ~ . " ' ' . .
z~639~ - 6 -biocompatible salt form ha~ a molecular weight of about 3.8 million Daltons, and has a viscosity in an aqueous 601ution of about 108 Pas. At this relatively high viscosity, hyaluronic acid or its biocompatible salt may be applied topically without ~xcessiv~ runnlne~ or dripping, thereby allowing the hyaluronic acid or it~ bioco~patible ~alt to remain in contact with the application area for a period of time (typically about 5 to about 10 minutes) su~icient to provide therapcu~ic value in retarding and rev~rsing the e~cts o~ h~rp~vi~us hominis in accordance W~th th~ p~a~ent inv~ntian.
Hyaluronic acid o~ lt~ blocompat~b~ 0al~
solutions having V~8C05iti~ th~n abou~ 0.
Pas ar~ generally not desired due ~o increased inconvenience in topical application.
It is believed that hyaluronic acid or its biocompatible salt form may be derived from any source using c~nventional processing techniques as long as the resulting hyaluronic acid has a visco~ity greater than about 0.4 Pas.
The salt form of hyaluronic acid according to the present invention must be biocompatible, preferably to about the same degree as hyaluronic acid. ~hus, the salt ~orm of hyaluronic acid , ,,. ~ . `,, ' , ; :
W090/14095 PCT/US90~02~43 2CS639~
~V,*
- 7 - ~ ,.
~hould not cause irritation or discomfort upon application, nor should the salt form of the hyaluronic acid have any other untoward effects whether or not related to the HSV infection. One example o~ a suitable biocompatible salt form o~
hyaluron~c acid includes sodium salt, ~orming ~odlum hyaluronate. One ~killed in the art, however, may readily determine, in view o~ the present specification and without undue experimentation, other biocompatible salt ~orms o~
hyaluronic acid which may b~ u~ed in accord~co with the presen~ inv~ntion.
Hy~luroni~ ~id or it~ bloaompatlbl~ ~lk ~orm ~ 5 pre~erabl~ ~ppli~d ln an a~uaou~ ~olution.
~he concentration o~ hyaluronic acid in such solution must be high enough, given the particular molecular weight o the hyaluronic acid, so that the solution has a viscosity greater than about 0.4 Pas and preferably greater than about 23 Pas for : :
relatively easy topical application. In one embodiment of the present invention, for exa~ple, hyaluronic acid having a molecular weight of about 500,000 Daltons is present in an aqueous solution :~:
in an amount of about 10 mg/ml and has a viscosity o~ about 0.4 Pas. In another, presently pre~erred Wo~o/14095 PCT/US90/02943 ~ ' . ' ZC5~39X - 8 -embodiment of the present invention, an aqueous solution of hyaluronic acid or its biocompatible salt having a molecular weight of about 3.8 million Daltons has a concentration of about 10 mq/ml and a viscosity o~ about 108 Pas.
Where hyaluronic a~id or its biocompatible salt i~ prezent in ~n aqUeous ~olution/ it may be desired to bu~er the solution to a given pH for greater or more consistent biocompatibility.
Generally, a pH o~ a~out 7.0 to about 7.4 is pr~erred ~or good biocompakibility ln topic~1 applications to a~eatad epithelia. Such buf~r~
should exhibit good bioccmp~ ility and ~hould not adver~ly e~ct th~ hyalu~onl~ a~ld ~r lt~
biocompatible ~alt ~orm. Examples o~ ~uitable bu~ers lnclude sodium phosphates, such as disodium hydrogen phosphate dihydrate ~nd sodium dihydrogen phosphate hydrate. One skilled in the art will appreciate, however, that other biocompatible 20 bu~fers may be used in accordance with the present ~ -invention.
Hyaluronic acid and its biocompatible salt forms suitable for treating herpesvirus hominis according to the present invention are commercially 25 available from manu~actures including Phar~aGia A~ , .. . . . . .. ~
W~0/14Q95 2~392 PCT/US90/02943 ' ', _ g _ ~ ~ .
D
in Sweden, MedChem Products, Inc., in Woburn, - -Massachusetts and Trans Bussan, S.A., Geneva, Switzerland. Pharmacia AB ~anufactures, for example, the Hylartin~ V sodium hyaluronate injection compound for American ~quine Products, Inc., South Norwalk Connecticut for intra-articular injection in hor~es. This partic~llar sodium hyaluronate has a molecular weight of about 3.
million Daltons in a buffered solution with a viscosity of about 108 Pas. This same sodium hyalurona~e preparation i~ also a~ailabl~ ~rom Pharmacia AB as thc produc~ H~lon ~or u~ in op~halmlc ~urgi~l proc~dur~. Thi~ p~apar~t~on i~
one exampl~ o~ a ~uitab~e biocompa~ibl~ ~alt -~rm of hyaluronic acid ~or use in accordance with the pres~nt invention.
Topical application o~ h~aluronic acid or its biocompatible salt form according to the present invention should be to human epithelia ~ -affected by the herpesvirus hominis, such as mucous and skin epithelia in the oral region (e.g., the :~:
lip) in the case of HSV-l infections, for example, and to the mucous and skin epithelia in the genital region in the case of HSV-2 infections, for example. Such application should substantially .
. . , : . . .
W O gO/]4095 ~ . PC~r/US90/02943 ~t.~
~ .
~S~;~3~2 - lo-totally cover the affected area. Those epithelia areas affected by ~Sv infection are general~y readily ascertainable in the precutaneous stage by the infected patient as those areas having a tingling and/or tender ~ensation or, ag $n many ~SV~2 infeatlo~s, a tend¢rnes~ in various ~u~cle groups in the areas surrounding the inf0ction, such as the muscles of the posterior thigh. In the cutaneous stage, affected areas are readily ascertainable as those areas o~ the epithelia contalning HSV induced le~ion~.
Testing o~ ~cvcral ~SV-l ln~cct~d ind~vi~uals in ~n uncon~clled cxpQrim~nt u~ing ~ho Hylart~n~ V sodium hyaluronat~ pr~para~ion ha~
indicated that ~reguent and liberal topical applications in accorda~ce with the present invention has several inhibitory e~fects on the immediate precutaneous and cutaneous stages of the ~SV-l infections. For example, during the completely manifested cutaneous stage of the HSV-1 infection, topical application according to this invention initiates an i~mediate (within 24 hours) reversal of the painful erythematic lesions. In addition, such application appesrs to reverse the 2S course o~ the cutaneous ~orm of the HSV-l infection W~90/l40~5 2~5~392 PCT/US90/02943 .~'~
and quicken its return to a latent state. Further, topical application according to this invention appears to 6horten the cutaneous phase of the i~fection and dramatically alleviate much of the as~ociated pain and discomfort.
While not wishing to be bound by any particular theoryr lt i~ believed that topical application o~ hyaluronic acid or its biocompatible salt form is best initiated when the HSV infection 10 i8 in the precukaneous ~orm. While toplcal applicatlon o~ hyaluronio ~cid ox it~ bloaompatiblc fo~m at this staga is recommand~d, topical applic~tion ~ lat~r stag~s m~y ~l~o ~ ~on~uc~od to allevia~e di~oom~ort and ~uick~n the return to latency. Topical application ~o affected epithelia thrice daily is presently believed to be effective to retard and reduce the effects of herpesvirus hominis~ Generally, application of hyaluronic acid or its biocompatible salt form should cover the affected area and ensured contact for at least about five to about ten minutes is presently believed to be satisfactory. ~;
The present invention may be embodied in other specific form~ without departing from the spiri~ or essential attributes thereof and, W09Otl409~ , PCT/US90/~2943 . ~. ~, . .. .... .. .
~ .' ' 2~392 - 12 -accordingly, reference should be made to the appended claims, rather than the specification, as indicating the scope of the invention.
.. -~ : . ........... .
.. ...
, . . , . . . .- .. . ~. .. ~ . : , . .: . ,:
hyaluronic acids is about 500,000 times more viscous than water alone. At a 10% by weight - :
' ~:
aqueous solution, hyaluronic acid is so viscous ' that it may be formed into ba'lls. Commercially available a~ueous solution~ generally have vi~cositie~ o~ abou~ 0.~ Pascal soconds ~Pas) to about 108 Pas (see W.E. ~ones, ~'Viscosupplementation in the Joint~ J. Equine Vet. ' ~
10 Sci. 9(2):102-04 (1989)). . '' Hyaluronic ac~d is an inhibitor o~ cell migration, a direct inhibitor o~ luukocykic activity, prev~nts th~ ~orm~tion c~ ~xc~ ibrau~
tiGsue ~nd i~ ~n anti-in~lamma~ory ~g~nt in m~ny uses. Previously ~ndwn u5e8 ~or hyaluronla acid are varie~, ranging rrOm its use to replace vitreous humor in opthalmic surgery, as an anti-inflammatory agent in veterinary medicine and as a vehicle in some cosmetic and pharmaceutical preparations.
8ummary of t~e Invention According to the present invention, a method of retarding and reversing the ef~ects o~
herpesvirus hominis comprises topically applying ~o W O 90/14095 2C~;~i392 P(~r/US9OtO2943 ,~ ' "' ' i - 5 ~ ; 3 human epithelia in an area affected by herpesvirus hominis, hyaluronic acid or its biocompatible salt form having a viscosity greater than about 0.4 Pascal seconds in amount effective to retard and reverse the effect6 of herpesvirus hominis.
Pre~erably, hyaluroni~ acld ~r its biocompatible ~alt ~o nD ha~ a VisC05ity in ~:olutlon c~ about 23 Pas to about 108 Pas and is prescnt in aqueous solution in an amount of about 1o mg/ml.
D~ C De~rlptlon ~ Pre~rra~ Embo~l~ent~
According to th~ pre~nt lnvcntion, the e~P~cts o~ herpQ0v~ru~ homini3 m~y b~ re~ard~d or revers~d by tapi~ally ~pply~ng to human ap~th~lla a~fected by herpesvirus hominis hyaluronic acid or iks biocompatibl~ salt ~o na. E~yaluronic acid or its biocompatible sal~ form should have a viscosity greater than about 0.4 Pas. It will be appreciated by one skill~d in the art in view of this disclosure that viscosity greater than about 0.4 2b Pas helps facilitate inunction or topical application of hyaluronic acid or its biocompatible ; salt form according to the present invention.
According to one embodi~ent o~ the present invention, for example, hyaluronic acid or its ;'' wos~/140~ PCT/US90/02943 . ,.. ~.. , ~ ' ' ~ . " ' ' . .
z~639~ - 6 -biocompatible salt form ha~ a molecular weight of about 3.8 million Daltons, and has a viscosity in an aqueous 601ution of about 108 Pas. At this relatively high viscosity, hyaluronic acid or its biocompatible salt may be applied topically without ~xcessiv~ runnlne~ or dripping, thereby allowing the hyaluronic acid or it~ bioco~patible ~alt to remain in contact with the application area for a period of time (typically about 5 to about 10 minutes) su~icient to provide therapcu~ic value in retarding and rev~rsing the e~cts o~ h~rp~vi~us hominis in accordance W~th th~ p~a~ent inv~ntian.
Hyaluronic acid o~ lt~ blocompat~b~ 0al~
solutions having V~8C05iti~ th~n abou~ 0.
Pas ar~ generally not desired due ~o increased inconvenience in topical application.
It is believed that hyaluronic acid or its biocompatible salt form may be derived from any source using c~nventional processing techniques as long as the resulting hyaluronic acid has a visco~ity greater than about 0.4 Pas.
The salt form of hyaluronic acid according to the present invention must be biocompatible, preferably to about the same degree as hyaluronic acid. ~hus, the salt ~orm of hyaluronic acid , ,,. ~ . `,, ' , ; :
W090/14095 PCT/US90~02~43 2CS639~
~V,*
- 7 - ~ ,.
~hould not cause irritation or discomfort upon application, nor should the salt form of the hyaluronic acid have any other untoward effects whether or not related to the HSV infection. One example o~ a suitable biocompatible salt form o~
hyaluron~c acid includes sodium salt, ~orming ~odlum hyaluronate. One ~killed in the art, however, may readily determine, in view o~ the present specification and without undue experimentation, other biocompatible salt ~orms o~
hyaluronic acid which may b~ u~ed in accord~co with the presen~ inv~ntion.
Hy~luroni~ ~id or it~ bloaompatlbl~ ~lk ~orm ~ 5 pre~erabl~ ~ppli~d ln an a~uaou~ ~olution.
~he concentration o~ hyaluronic acid in such solution must be high enough, given the particular molecular weight o the hyaluronic acid, so that the solution has a viscosity greater than about 0.4 Pas and preferably greater than about 23 Pas for : :
relatively easy topical application. In one embodiment of the present invention, for exa~ple, hyaluronic acid having a molecular weight of about 500,000 Daltons is present in an aqueous solution :~:
in an amount of about 10 mg/ml and has a viscosity o~ about 0.4 Pas. In another, presently pre~erred Wo~o/14095 PCT/US90/02943 ~ ' . ' ZC5~39X - 8 -embodiment of the present invention, an aqueous solution of hyaluronic acid or its biocompatible salt having a molecular weight of about 3.8 million Daltons has a concentration of about 10 mq/ml and a viscosity o~ about 108 Pas.
Where hyaluronic a~id or its biocompatible salt i~ prezent in ~n aqUeous ~olution/ it may be desired to bu~er the solution to a given pH for greater or more consistent biocompatibility.
Generally, a pH o~ a~out 7.0 to about 7.4 is pr~erred ~or good biocompakibility ln topic~1 applications to a~eatad epithelia. Such buf~r~
should exhibit good bioccmp~ ility and ~hould not adver~ly e~ct th~ hyalu~onl~ a~ld ~r lt~
biocompatible ~alt ~orm. Examples o~ ~uitable bu~ers lnclude sodium phosphates, such as disodium hydrogen phosphate dihydrate ~nd sodium dihydrogen phosphate hydrate. One skilled in the art will appreciate, however, that other biocompatible 20 bu~fers may be used in accordance with the present ~ -invention.
Hyaluronic acid and its biocompatible salt forms suitable for treating herpesvirus hominis according to the present invention are commercially 25 available from manu~actures including Phar~aGia A~ , .. . . . . .. ~
W~0/14Q95 2~392 PCT/US90/02943 ' ', _ g _ ~ ~ .
D
in Sweden, MedChem Products, Inc., in Woburn, - -Massachusetts and Trans Bussan, S.A., Geneva, Switzerland. Pharmacia AB ~anufactures, for example, the Hylartin~ V sodium hyaluronate injection compound for American ~quine Products, Inc., South Norwalk Connecticut for intra-articular injection in hor~es. This partic~llar sodium hyaluronate has a molecular weight of about 3.
million Daltons in a buffered solution with a viscosity of about 108 Pas. This same sodium hyalurona~e preparation i~ also a~ailabl~ ~rom Pharmacia AB as thc produc~ H~lon ~or u~ in op~halmlc ~urgi~l proc~dur~. Thi~ p~apar~t~on i~
one exampl~ o~ a ~uitab~e biocompa~ibl~ ~alt -~rm of hyaluronic acid ~or use in accordance with the pres~nt invention.
Topical application o~ h~aluronic acid or its biocompatible salt form according to the present invention should be to human epithelia ~ -affected by the herpesvirus hominis, such as mucous and skin epithelia in the oral region (e.g., the :~:
lip) in the case of HSV-l infections, for example, and to the mucous and skin epithelia in the genital region in the case of HSV-2 infections, for example. Such application should substantially .
. . , : . . .
W O gO/]4095 ~ . PC~r/US90/02943 ~t.~
~ .
~S~;~3~2 - lo-totally cover the affected area. Those epithelia areas affected by ~Sv infection are general~y readily ascertainable in the precutaneous stage by the infected patient as those areas having a tingling and/or tender ~ensation or, ag $n many ~SV~2 infeatlo~s, a tend¢rnes~ in various ~u~cle groups in the areas surrounding the inf0ction, such as the muscles of the posterior thigh. In the cutaneous stage, affected areas are readily ascertainable as those areas o~ the epithelia contalning HSV induced le~ion~.
Testing o~ ~cvcral ~SV-l ln~cct~d ind~vi~uals in ~n uncon~clled cxpQrim~nt u~ing ~ho Hylart~n~ V sodium hyaluronat~ pr~para~ion ha~
indicated that ~reguent and liberal topical applications in accorda~ce with the present invention has several inhibitory e~fects on the immediate precutaneous and cutaneous stages of the ~SV-l infections. For example, during the completely manifested cutaneous stage of the HSV-1 infection, topical application according to this invention initiates an i~mediate (within 24 hours) reversal of the painful erythematic lesions. In addition, such application appesrs to reverse the 2S course o~ the cutaneous ~orm of the HSV-l infection W~90/l40~5 2~5~392 PCT/US90/02943 .~'~
and quicken its return to a latent state. Further, topical application according to this invention appears to 6horten the cutaneous phase of the i~fection and dramatically alleviate much of the as~ociated pain and discomfort.
While not wishing to be bound by any particular theoryr lt i~ believed that topical application o~ hyaluronic acid or its biocompatible salt form is best initiated when the HSV infection 10 i8 in the precukaneous ~orm. While toplcal applicatlon o~ hyaluronio ~cid ox it~ bloaompatiblc fo~m at this staga is recommand~d, topical applic~tion ~ lat~r stag~s m~y ~l~o ~ ~on~uc~od to allevia~e di~oom~ort and ~uick~n the return to latency. Topical application ~o affected epithelia thrice daily is presently believed to be effective to retard and reduce the effects of herpesvirus hominis~ Generally, application of hyaluronic acid or its biocompatible salt form should cover the affected area and ensured contact for at least about five to about ten minutes is presently believed to be satisfactory. ~;
The present invention may be embodied in other specific form~ without departing from the spiri~ or essential attributes thereof and, W09Otl409~ , PCT/US90/~2943 . ~. ~, . .. .... .. .
~ .' ' 2~392 - 12 -accordingly, reference should be made to the appended claims, rather than the specification, as indicating the scope of the invention.
.. -~ : . ........... .
.. ...
, . . , . . . .- .. . ~. .. ~ . : , . .: . ,:
Claims (13)
1. A method of retarding and reversing the effects of herpesvirus hominis, which comprises topically applying to human epithelia in an area affected by herpesvirus hominis, hyaluronic acid or its biocompatible salt form having a viscosity greater than about 0.4 Pascal seconds in an amount effective to retard and reverse the effect of herpesvirus hominis.
2. The method according to claim 1, wherein the epithelia is mucous membrane.
3. The method according to claim 1, wherein the epithelia is lip tissue.
4. The method according to claim 1, wherein the epithelia is genital epithelia.
5. The method according to claim 1, wherein the herpesvirus hominis is Type I
herpesvirus hominis.
herpesvirus hominis.
6. The method according to claim 1, wherein the herpesvirus hominis is Type II
herpesvirus hominis.
herpesvirus hominis.
7. The method according to claim 1, wherein the viscosity of the hyaluronic acid or its biocompatible salt form is greater than about 23 Pascal seconds.
8. The method according to claim 1, wherein the biocompatible salt form is sodium hyaluronate.
9. The method according to claim 1, wherein the hyaluronic acid or its biocompatible salt form is present in a buffered aqueous solution.
10. The method according to claim 9, wherein the hyaluronic acid or its biocompatible salt form is present in solution in an amount of about 10 mg/ml.
11. The method according to claim 9, wherein the aqueous solution is buffered with a sodium phosphate.
12. The method according to claim 11, wherein the sodium phosphate is selected from the group consisting of disodium hydrogen phosphate and sodium dihydrogen phosphate.
13. The method according to claim 1, wherein the hyaluronic acid or its biocompatible salt form is applied thrice daily in an amount sufficient to substantially totally cover the affected area.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35738589A | 1989-05-26 | 1989-05-26 | |
| US357,385 | 1989-05-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2056392A1 true CA2056392A1 (en) | 1990-11-27 |
Family
ID=23405357
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002056392A Abandoned CA2056392A1 (en) | 1989-05-26 | 1990-05-24 | Topical treatment of herpesvirus hominis |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU5670990A (en) |
| CA (1) | CA2056392A1 (en) |
| WO (1) | WO1990014095A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5550112A (en) * | 1992-12-30 | 1996-08-27 | Patent Biopharmaceutics, Inc. | Hyaluronic acid-urea pharmaceutical compositions and uses |
| WO2003041723A1 (en) * | 2001-11-12 | 2003-05-22 | Reinmueller Johannes | Pharmaceutical applications of hyaluronic acid preparations |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0066283B1 (en) * | 1981-06-02 | 1986-09-10 | Eupan Corporation | Eustatic composition for nonspecifically facilitating and amplifying the generalized homeostatic regulation and maintenance, compensation and repair in living organisms |
| US4711780A (en) * | 1984-06-11 | 1987-12-08 | Fahim Mostafa S | Composition and process for promoting epithelial regeneration |
-
1990
- 1990-05-24 CA CA002056392A patent/CA2056392A1/en not_active Abandoned
- 1990-05-24 WO PCT/US1990/002943 patent/WO1990014095A1/en active Application Filing
- 1990-05-24 AU AU56709/90A patent/AU5670990A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU5670990A (en) | 1990-12-18 |
| WO1990014095A1 (en) | 1990-11-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5118633B2 (en) | Mucoadhesive xyloglucan-containing preparations useful in medical devices and pharmaceutical preparations | |
| CA2310207C (en) | Topical zinc compositions and methods of use | |
| US6476005B1 (en) | Oral and injectable nutritional composition | |
| US6645948B2 (en) | Nutritional composition for the treatment of connective tissue | |
| AU617111B2 (en) | Repairing agent for cells and tissues | |
| US6346271B1 (en) | Topical drug preparations | |
| JP4010574B2 (en) | Topical skin preparation | |
| KR100761051B1 (en) | Pharmaceutical composition for the treatment of mucositis, stomatitis and Behcet's syndrome | |
| US20060094643A1 (en) | Compositions of hyaluronic acid and methods of use | |
| JPH08502074A (en) | Tissue protection and regeneration composition | |
| JP4005628B2 (en) | Topical composition containing hyaluronic acid and NSAIDS (non-steroidal anti-inflammatory agent) | |
| JP2001505546A (en) | Antibacterial treatment for herpes simplex virus and other infectious diseases | |
| JPH0739347B2 (en) | Uses of sulfated sugars | |
| KR20010013349A (en) | Device and Methods for Wound Treatment | |
| CA2090749A1 (en) | Composition for nasal treatment | |
| EP0305551A2 (en) | Pharmaceutical compositions for topical application | |
| JPH11514967A (en) | Use of hyaluronic acid and NSAIDs for the manufacture of a medicament for the treatment of mucosal inflammation | |
| WO2002094256A1 (en) | Lysine and/or analogues and/or polymers thereof for promoting wound healing and angiogenesis | |
| US6387407B1 (en) | Topical drug preparations | |
| US4957734A (en) | Treatment of certain skin malignancies and pre-malignant skin lesions, herpes zoster and psoriasis | |
| MXPA03011613A (en) | Ophthalmic composition containing n-acetylcysteine for the treat ment of dry-eye syndrome. | |
| CA2056392A1 (en) | Topical treatment of herpesvirus hominis | |
| JP3050898B2 (en) | Aqueous pharmaceutical preparation | |
| CN106491634A (en) | Hyaluronic Acid dimethyl-silicon alkanol complex and combinations thereof | |
| JPS60233018A (en) | Insulin medicine for treating normal acne |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |