CA1083040A - Topical application of medication by ultrasound with coupling agent - Google Patents
Topical application of medication by ultrasound with coupling agentInfo
- Publication number
- CA1083040A CA1083040A CA271,202A CA271202A CA1083040A CA 1083040 A CA1083040 A CA 1083040A CA 271202 A CA271202 A CA 271202A CA 1083040 A CA1083040 A CA 1083040A
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/05—General characteristics of the apparatus combined with other kinds of therapy
- A61M2205/058—General characteristics of the apparatus combined with other kinds of therapy with ultrasound therapy
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Inorganic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Medical Informatics (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
Abstract of the Disclosure A method of topically applying an effective medication in an emulsion coupling agent by ultrasound.
More particularly, a method of treating a skin condition by applying a medication in an emulsion coupling agent and massaging it into the affected area with ultrasonic vibrations thereby causing the medication to penetrate into the skin. Specifically, a method and composition for the treatment of Herpes Simplex Type 1 and Type 2 lesions. Also specifically, a method and composition for the treatment of demidox mites.
More particularly, a method of treating a skin condition by applying a medication in an emulsion coupling agent and massaging it into the affected area with ultrasonic vibrations thereby causing the medication to penetrate into the skin. Specifically, a method and composition for the treatment of Herpes Simplex Type 1 and Type 2 lesions. Also specifically, a method and composition for the treatment of demidox mites.
Description
The present lnventlon relates to a method o~
treatlng a skin condition wlth an e~rective medication by applying it with ultrasonlc vlbrations through a coupling agent such as oll. More particularly, the present lnvent-ion relates.to a method ror applylng an efrective antiviral drug to Herpes Simplex lesions by ultrasound and to t~e com-posltions thereof. It also relates to a method for applying an errective medlcation to demidox mites by ultrasound and to the composition thereor.
Herpes Simplex is an ~nrectious disease having two ma~or serotypes of the causative virus. As a general rule, Type 1 virus is responslble ror oral herpes and other skin lesions above the waist.- Type 2 virus, on the other hand, is usually responsible ror genital herpes~ other skin lesions below the waist and ~or neonatal herpes.
The two serotypes difrer in thelr cytopathic ef~ect on cells in tissue culture, virulence ~or laboratory animals, behavior on embryonated chicken eggs and, as mentioned above, their usual site on the body. Both types, however, can occur outside of its usual loca~ion and with changing mores, more and more cases Or genital herpes are caused by Type 1 virus. Oc-casionally, neonatal herpes is also caused by Type 1 virus. The occurrence Gr genital herpes is on the riseg particularly among young people. The disease is classified as venereal and is re-garded as a serious medical problem.
The clinical manirestations of oral and genital herpes vary rrom individual to individual but the disease usually appears as a series Or veslcles. In the case Or oral herpes, the disease may mani~est itself as fever blisters or as lesions on the lip~ or ~ace. The lesions are self-limiting and usually heal in about 7 to 14 days but are troublesome .
~1 ~ 33~4~
Io the patient causlng ltchlng and burning and are somewhat .~ 1 S ri guring.
Genltal herpes is more serious and can be ver~
pain~ul, especially in women. In remales, genital herpes can be dif~use and involve the entire vulva~ oriflce Or the vagina, cervix and cervical end Or the vagina. B1-lateral inguinal lymphadenopathy ls the rule. When the vesicles are diffuse, the ma~ority Or women have systemlc manifestations such as chill, fever and general aching.
Dysuria and dyspareunia are common. Occasionally, there is acute urinary retention due to rerlex spasm of the urethral sphincter.
In males, genital herpes usually consists o~
vesicles on the glans o~ the penis or on the penis~ The lesions may be painrul but systemic mani~estations are un-common.
In most patients overt recurrent Herpes Simplex lesions do not appear but in other individuals, recurrences -~are common. The duration and rrequency Or reactivatlon of the infection varies considerably, but the course o~ the disease tends to remaln rairly constant ln any given individual~
These recurrences may be provoked by excitants, such as re- -~ver, sunshlne, gastrointestinal upsets, mechanical trauma, allergy, repressed anxiety or hostility or menstrual periods and are known to be more common during pregnancy. Frequent recurrences are distresslng to the patient, and for women ~enital herpes take~ on additional slgnificance because Or --the suspected association of Type 2 Herpes Simplex and carcinoma Or the cervix and because Or the serious nature of neonatal herpes transmitted rrom mother to inrant during --~ate pregnancy and dellvery.
~ .
3~
In the past, ultrasound has been used to re-lieve symptoms Or musculoskeletal disorders and to clean and treat open wounds. Numerous treatments ror Herpes Simplex les~ons have been tried. In the case Or genital herpes, one Or the more common methods involves painting inrected areas with acridine dyes and then exposing them to llght. This treatment has been crlticised as a potent ial danger in itself because the inactivated viruses may still be able to transrorm normal mammalian cells into cells with new inheritable characteristics and with loss Or contact inhibition, which characteristics are orten as-soclated wlth a malignant potential.
In view of the above, among the several ob~ects Or the present invention is the provision o~ a method ~or treating a skin condition with an efrective medication by applying it with ultrasonic vibrations through a coupling agent such as oil~ More specifically, the ob~ect o~ the present invention is the provision of a method for treat-ing Herpes Simplex involving the application Or an effect-ive antiviral drug such as urea to the afrected area by ultrasound, said method facilitating the administration o~
the antiviral drug intracellularly. Other obJects and fea-tures will be in part apparent and in part pointed out here-inarter .
The invention accordingly comprises the methods and compositions hereinafter described, the scope of the inventlon being indicated in the following claims.
In accordance with the present invention, skin conditions in man or other animals are treated with an ef-fective medication which is applied to the afrected area 33~
and then directly mlcromassaged thereln by ultrasonic vibrations through a coupling agent such as oil.
More particularly, lesions caused by Herpes Simplex are treated with an antiviral drug which is er-fective against Herpes Simplex and directly applied wlth ultrasonic vlbrations.
Suitable antiviral-drugs effective for the pre-sent purpose include urea, idoxuridine, amantadine, meth-isazone~ cytarabine, interrerons or the like. In the pre-ferred rorm, a medicament containing an effective amount of the antiv~ral drug is flrst made up. In general, the medicament contains ~rom about 5 to about 40 percent by welght o~ the antiviral drug. In treating Herpes Simplex~
urea is often selected as the antiviral drug because it is also erfective against cancer. When the drug is urea and the medicament is ror treatment of oral herpes, it gener-ally contains ~rom about 10 percent by welght to about 30 percent by weight Or urea, and when it is for treat-ment of genital herpes, it contains from about 10 percent ~20 by weight to about 40 percent by weight Or urea.
More preferred medlcaments ~or treatment Or oral Herpes Simplex contain rrom about 20 percent to about 30 percent by weight Or urea and ~or treatment of genital Her-pes Simplex contain from about 30 percent by weight to about 40 percent by weight. Especially preferred are medicaments containing about 30 percent by weight Or urea for treatment Or oral herpes or genital herpes.
Usually, the medicament includes other materials to accelerate or otherwise promote healing. W~en the medi-cament is ror oral application, such materials lnclude zinc 3~4~
oxlde, tannic acid~ menthol) ethyl alcohol or the like .
For this purpose, the zinc oxide ls present in an amount rrom about 0.5 percent by weight to about 3 percent by weight 3 pre~erably from about 1 percent by weight to -about 3 percent by weight and more pre~erably from about 1.5 percent by weight to about 2 percent by weight.
Zinc compounds such as zinc oxide are included because zinc amplifies the mechanical efrects Or the ultra-sonic vibrations to break the viral membranes so that the 0 antlviral drug is administered intracellularly. More- ;
over, zinc oxide functions as an astringent, as a corro-sive to promote healing and as a mild antiseptic.
Tannic acid is included because it is an astrin-gent and precipitates protein with heavy metal ions such as zinc. Since Herpes Simplex viruses are protein, the combined ef~ect o~ zinc oxide and tannic acid is to kill the virus.
Menthol is added to the lip ~ormulation because it gives a cool feeling and relie~es itching. Ethyl alco-hol is included as a mild antiseptic because patients orten scratch their blisters and cause secondary ~nrection there-in.
The tannic acid is present in an amount from about 0.5 percent by we~ght to about 2 percent by weight, pre~er-ably ~rom about 0.5 percent by weight to about 1.5 percent ; by weight and more preferably from about 1 percent by weight to about 1.5 percent by weight.
The menthol is present in an amount ~rom about 0.25 percent by weight to about 1 percent by weight, preferably 3 from about 0.25 percent by weight to about 0.75 percent by ~ 836~
welght and more preferably ~rom about 0.30 percent by weight to about 0.50 percent by welght.
The ethyl alcohol is present in an amount ~rom about n . 30 percent by weight to about 1.0 percent by weight, prererably ~rom about 0.30 percent by weight to about 0.75 percent by weight and more prererably ~rom about 0.30 per-cent by weight to about 0O50 percent by weight.
When the medlcament is ~or genital application, the materials to accelerate or otherwise promote healing are the same as for oral application except that menthol and ethyl alcohol are eliminated. In this case, the zinc oxide is present in an amount rrom about 1 percent by weight to about 5 percent by weight, preferably from about 2 percent by weight to about ~ percent by weight and more preferably rrom about .. .
treatlng a skin condition wlth an e~rective medication by applying it with ultrasonlc vlbrations through a coupling agent such as oll. More particularly, the present lnvent-ion relates.to a method ror applylng an efrective antiviral drug to Herpes Simplex lesions by ultrasound and to t~e com-posltions thereof. It also relates to a method for applying an errective medlcation to demidox mites by ultrasound and to the composition thereor.
Herpes Simplex is an ~nrectious disease having two ma~or serotypes of the causative virus. As a general rule, Type 1 virus is responslble ror oral herpes and other skin lesions above the waist.- Type 2 virus, on the other hand, is usually responsible ror genital herpes~ other skin lesions below the waist and ~or neonatal herpes.
The two serotypes difrer in thelr cytopathic ef~ect on cells in tissue culture, virulence ~or laboratory animals, behavior on embryonated chicken eggs and, as mentioned above, their usual site on the body. Both types, however, can occur outside of its usual loca~ion and with changing mores, more and more cases Or genital herpes are caused by Type 1 virus. Oc-casionally, neonatal herpes is also caused by Type 1 virus. The occurrence Gr genital herpes is on the riseg particularly among young people. The disease is classified as venereal and is re-garded as a serious medical problem.
The clinical manirestations of oral and genital herpes vary rrom individual to individual but the disease usually appears as a series Or veslcles. In the case Or oral herpes, the disease may mani~est itself as fever blisters or as lesions on the lip~ or ~ace. The lesions are self-limiting and usually heal in about 7 to 14 days but are troublesome .
~1 ~ 33~4~
Io the patient causlng ltchlng and burning and are somewhat .~ 1 S ri guring.
Genltal herpes is more serious and can be ver~
pain~ul, especially in women. In remales, genital herpes can be dif~use and involve the entire vulva~ oriflce Or the vagina, cervix and cervical end Or the vagina. B1-lateral inguinal lymphadenopathy ls the rule. When the vesicles are diffuse, the ma~ority Or women have systemlc manifestations such as chill, fever and general aching.
Dysuria and dyspareunia are common. Occasionally, there is acute urinary retention due to rerlex spasm of the urethral sphincter.
In males, genital herpes usually consists o~
vesicles on the glans o~ the penis or on the penis~ The lesions may be painrul but systemic mani~estations are un-common.
In most patients overt recurrent Herpes Simplex lesions do not appear but in other individuals, recurrences -~are common. The duration and rrequency Or reactivatlon of the infection varies considerably, but the course o~ the disease tends to remaln rairly constant ln any given individual~
These recurrences may be provoked by excitants, such as re- -~ver, sunshlne, gastrointestinal upsets, mechanical trauma, allergy, repressed anxiety or hostility or menstrual periods and are known to be more common during pregnancy. Frequent recurrences are distresslng to the patient, and for women ~enital herpes take~ on additional slgnificance because Or --the suspected association of Type 2 Herpes Simplex and carcinoma Or the cervix and because Or the serious nature of neonatal herpes transmitted rrom mother to inrant during --~ate pregnancy and dellvery.
~ .
3~
In the past, ultrasound has been used to re-lieve symptoms Or musculoskeletal disorders and to clean and treat open wounds. Numerous treatments ror Herpes Simplex les~ons have been tried. In the case Or genital herpes, one Or the more common methods involves painting inrected areas with acridine dyes and then exposing them to llght. This treatment has been crlticised as a potent ial danger in itself because the inactivated viruses may still be able to transrorm normal mammalian cells into cells with new inheritable characteristics and with loss Or contact inhibition, which characteristics are orten as-soclated wlth a malignant potential.
In view of the above, among the several ob~ects Or the present invention is the provision o~ a method ~or treating a skin condition with an efrective medication by applying it with ultrasonic vibrations through a coupling agent such as oil~ More specifically, the ob~ect o~ the present invention is the provision of a method for treat-ing Herpes Simplex involving the application Or an effect-ive antiviral drug such as urea to the afrected area by ultrasound, said method facilitating the administration o~
the antiviral drug intracellularly. Other obJects and fea-tures will be in part apparent and in part pointed out here-inarter .
The invention accordingly comprises the methods and compositions hereinafter described, the scope of the inventlon being indicated in the following claims.
In accordance with the present invention, skin conditions in man or other animals are treated with an ef-fective medication which is applied to the afrected area 33~
and then directly mlcromassaged thereln by ultrasonic vibrations through a coupling agent such as oil.
More particularly, lesions caused by Herpes Simplex are treated with an antiviral drug which is er-fective against Herpes Simplex and directly applied wlth ultrasonic vlbrations.
Suitable antiviral-drugs effective for the pre-sent purpose include urea, idoxuridine, amantadine, meth-isazone~ cytarabine, interrerons or the like. In the pre-ferred rorm, a medicament containing an effective amount of the antiv~ral drug is flrst made up. In general, the medicament contains ~rom about 5 to about 40 percent by welght o~ the antiviral drug. In treating Herpes Simplex~
urea is often selected as the antiviral drug because it is also erfective against cancer. When the drug is urea and the medicament is ror treatment of oral herpes, it gener-ally contains ~rom about 10 percent by welght to about 30 percent by weight Or urea, and when it is for treat-ment of genital herpes, it contains from about 10 percent ~20 by weight to about 40 percent by weight Or urea.
More preferred medlcaments ~or treatment Or oral Herpes Simplex contain rrom about 20 percent to about 30 percent by weight Or urea and ~or treatment of genital Her-pes Simplex contain from about 30 percent by weight to about 40 percent by weight. Especially preferred are medicaments containing about 30 percent by weight Or urea for treatment Or oral herpes or genital herpes.
Usually, the medicament includes other materials to accelerate or otherwise promote healing. W~en the medi-cament is ror oral application, such materials lnclude zinc 3~4~
oxlde, tannic acid~ menthol) ethyl alcohol or the like .
For this purpose, the zinc oxide ls present in an amount rrom about 0.5 percent by weight to about 3 percent by weight 3 pre~erably from about 1 percent by weight to -about 3 percent by weight and more pre~erably from about 1.5 percent by weight to about 2 percent by weight.
Zinc compounds such as zinc oxide are included because zinc amplifies the mechanical efrects Or the ultra-sonic vibrations to break the viral membranes so that the 0 antlviral drug is administered intracellularly. More- ;
over, zinc oxide functions as an astringent, as a corro-sive to promote healing and as a mild antiseptic.
Tannic acid is included because it is an astrin-gent and precipitates protein with heavy metal ions such as zinc. Since Herpes Simplex viruses are protein, the combined ef~ect o~ zinc oxide and tannic acid is to kill the virus.
Menthol is added to the lip ~ormulation because it gives a cool feeling and relie~es itching. Ethyl alco-hol is included as a mild antiseptic because patients orten scratch their blisters and cause secondary ~nrection there-in.
The tannic acid is present in an amount from about 0.5 percent by we~ght to about 2 percent by weight, pre~er-ably ~rom about 0.5 percent by weight to about 1.5 percent ; by weight and more preferably from about 1 percent by weight to about 1.5 percent by weight.
The menthol is present in an amount ~rom about 0.25 percent by weight to about 1 percent by weight, preferably 3 from about 0.25 percent by weight to about 0.75 percent by ~ 836~
welght and more preferably ~rom about 0.30 percent by weight to about 0.50 percent by welght.
The ethyl alcohol is present in an amount ~rom about n . 30 percent by weight to about 1.0 percent by weight, prererably ~rom about 0.30 percent by weight to about 0.75 percent by weight and more prererably ~rom about 0.30 per-cent by weight to about 0O50 percent by weight.
When the medlcament is ~or genital application, the materials to accelerate or otherwise promote healing are the same as for oral application except that menthol and ethyl alcohol are eliminated. In this case, the zinc oxide is present in an amount rrom about 1 percent by weight to about 5 percent by weight, preferably from about 2 percent by weight to about ~ percent by weight and more preferably rrom about .. .
2.5 percent by weight to about 3 percent by weight.
The tannic acid is present in an amount from about 1 percent by weight to about 5 percent by weight~ preferably rrom about 2 percent by weight to about 4 percent by weight and more prererably rrom about 3 percent by welght to about 4 percent.
Since ultrasound does not transmit through air, the me~icament must provide a coupling between the ultra-sonic applicator and the skin to be treated. IFor this purpose, the medicament usually contalns oil or similar material so ?5 there are no air gaps between the applicator and the under-lying skin~
The particular coupling agent selected is preferably non-stainlng, non-irritating and slow drying. The nature and amount of coupling agent is selected so that the~resultant paste or gel is not so ~luid at body temperature that is ~lows from .
. ' .
~3~4~
between khe ultrasonic applicator and the skin resulting ln poor or no ultrasonic coupling.
Suitable coupling agents lnclude mlxtures o~ mineral oil and glycerln or the like b~t the prererred coupling a~ent ,.,.,, ,~ .
~i is HEB cream sold by Barnes Hind Company. This material is a mixture of cetyl alcohol, stearyl alcohol, white petrolatum9 mineral oil and propylene glycol. When the medicamenk is for oral application and the coupling agent is HEB cream, the coupl-ing agent is present in an amount from about 65 to about 70, pre~erably from about 65 to about 67 and more preferably rrom about 65 to 66 percent by weight. When the medicament is for genital application and the coupling agent is HEB cream, the coupling agent is present in an amount ~rom about 60 per-cent to about 7G percent by weight, preferably ~rom about 60 to about 68 and more prererably ~rom about 60 to 65. Other formulations based on other coupling agents can be readily determined by one skilled in the art given the properties re-quired thereo~ as descrlbed above. -- - -The medicament is made up by combining the above-rnentioned materials_in the amounts described and by blending them until a paste or gel is rormed. Since the medicament is shel~ stable, it-may be prepared in advance and skored.
l~en the medicament is ready for use, the patient is com~ortably positioned and his lesions examined. An amount ~5 Or medicament ls rubbed onto the area to be treated in an amount su~icient to assure good coupling between the ultra-sonic applicator and the skin to be treated.
.
~ ~r~e ~har3( ~ -
The tannic acid is present in an amount from about 1 percent by weight to about 5 percent by weight~ preferably rrom about 2 percent by weight to about 4 percent by weight and more prererably rrom about 3 percent by welght to about 4 percent.
Since ultrasound does not transmit through air, the me~icament must provide a coupling between the ultra-sonic applicator and the skin to be treated. IFor this purpose, the medicament usually contalns oil or similar material so ?5 there are no air gaps between the applicator and the under-lying skin~
The particular coupling agent selected is preferably non-stainlng, non-irritating and slow drying. The nature and amount of coupling agent is selected so that the~resultant paste or gel is not so ~luid at body temperature that is ~lows from .
. ' .
~3~4~
between khe ultrasonic applicator and the skin resulting ln poor or no ultrasonic coupling.
Suitable coupling agents lnclude mlxtures o~ mineral oil and glycerln or the like b~t the prererred coupling a~ent ,.,.,, ,~ .
~i is HEB cream sold by Barnes Hind Company. This material is a mixture of cetyl alcohol, stearyl alcohol, white petrolatum9 mineral oil and propylene glycol. When the medicamenk is for oral application and the coupling agent is HEB cream, the coupl-ing agent is present in an amount from about 65 to about 70, pre~erably from about 65 to about 67 and more preferably rrom about 65 to 66 percent by weight. When the medicament is for genital application and the coupling agent is HEB cream, the coupling agent is present in an amount ~rom about 60 per-cent to about 7G percent by weight, preferably ~rom about 60 to about 68 and more prererably ~rom about 60 to 65. Other formulations based on other coupling agents can be readily determined by one skilled in the art given the properties re-quired thereo~ as descrlbed above. -- - -The medicament is made up by combining the above-rnentioned materials_in the amounts described and by blending them until a paste or gel is rormed. Since the medicament is shel~ stable, it-may be prepared in advance and skored.
l~en the medicament is ready for use, the patient is com~ortably positioned and his lesions examined. An amount ~5 Or medicament ls rubbed onto the area to be treated in an amount su~icient to assure good coupling between the ultra-sonic applicator and the skin to be treated.
.
~ ~r~e ~har3( ~ -
3~
The medicament is then micromassaged lnto the arrected area by ultrasonic vibrations. For this purpose, an ultrasonlc applicator is slowly moved back and rorth over the leslons, either in a rotary or transverse direction, in order to reduce the concentration of energy at any given point. The pressure applied through the applicator is light but is rirm enough to maintain good coupling. In treating patients having lesions which are particularly pain~ul and sensitive to heat, the ultrasonic applicator, which includes a transducer within an applicator houslng, is preferably water cooled.
The length Or the treatment, output frequency Or the ultrasonic generator coupled to the applicator and power level at the applicator surface will vary in the individual case and is up to the physician. Preferably, however, the output rrequency Or the generator is about 1000 KHZ and the power level at the applicator head is about 1.0 to 3.0 watts per sq. cm~ A suitable ultrasonic generator for this purpose is manufactured by Whitewater Electronics, Inc. and has a 20 _= .. =frequency of 1100 XHZ + 10 KHZ, a continuous power output Or 0 to 32 watts and an erfective power level at the applicator head Or 3.0 watts per sq. cm.
The rrequency and number Or treatments is deter-mined individually at the discretion Or the physician. Orten to begin with, treatments are given daily ~or 2 to 3 minutes and then reduced in rrequency when desired efrects are ob-tained. It is not unusual, however~ that only one treatment is necessary berore beneficial efrects become a~parent.
The rollowing examples illustrate the invention~
: ~ _ 9 _ ~ .
~ 3~ ~
An e~recti~e medicament (HERPIGON LOTION I) ror the treatment Or Herpes Slmplex Type 1 lesions by ultra-sound was prepared by blending the following materials:
.
In~redient Percent by Weight Urea . 3 Zinc oxide 2 Tannic acid Menthol .5 HEB cream 66 Ethyl alcohol . qs .
EXAMPLE Z
.To demonstrate that ultrasonic vibrations cause HERPIGON LOTION I to penetrate tissues through the skin, sixty rats were chosen, their backs shaved and treated as rOllOws: - -: Ten rats were selected ~or each o~ three tests in Group A. In each tes~, radioactive HERPIGON LOTION I
was rubbed onto the shaved backs o~ the rats. As shown in Table A, in Test 1 the radioactive component o~ the HERPIGON
LOTION I was tannic acid, ln Test ~ it was urea and in Test 3 it was a combination Or tannic acid and ureaO Otherwlse9 the HERPIGON LOTION I used in these tests was prepared as in Example 1~
' TABLE A
Rad~oactive Component Test 1, Test 4 Tannic acid (H3) Test 2, Test 5 Urea (C14) Test 3, Test 6 Tannic acid (H3) and Urea (C14 . . .
~ j l ~33~D4~
Ten rats were selected for each o~ three tests in Group B. In each test, radioactive HERPIGON LOTION I
was rubbed ~nto the shaved backs o~ the rats and micro-massaged therein with ultrasound ror about 5 minukes. An ultrasonlc generator with a f'requency of 1100 KHZ ~ 10KHZ -was coupled to an ultrasonic applicator. The applicator head measured 2.5 sq. cm. and had an efrectlve power level of 1 watt per sq. cm. As shown in Table A, the radioactive components of the HERPIGON LOTION I in Tests 4, 5 and 6 were the same as in Tests 1, 2 and 3, respectively.
All Or the rats in Groups A and B were sacrificed and vertical sections 1 inch thick including the skin were taken rrom their back muscles. Slices were then made, ~ixed ; and analyzed by autoradiographic localization ror penetration Or the radioactive drugs. The results show that both radio-- active urea and tannic acid are caused to enter the muscle _to a depth Or from about 1/2 inch to about 1 inch when they are applled with ultrasonic vibrations. When they are ap-plied without vibrations, they remain on the surface o~ the skin and do not penetrate the muscle.
Ten sub~ects su~fering oral herpes were chosen on the basis Or visible evidence of active lesions on the lips, inside Or the lips or mouth. Each had 3 or 4 vesicles and came in for treatment between 12 and 24 hours after appearance of the blisters. A sample was taken by cotton swab rrom the inrected area Or each sub~ect and preserved in a special media for virus culture. The virus h~as identified as Herpes Simplex ; 3o Type 1 by culture and by electron microscopy.
Five of the subJects were selected for a control group. They were treated by rubblng an ultrasonic applicator ;
r ~3~
head as described in Example 2 over the infected area for two minutes~ The control patients reported that itching continued ror 4 to 7 days and that the blisters took rrom 7 to 12 days to disappear.
me other five sub~ects were selected for an active treatment group acsording to the present lnvent-ionO An amount o~ HERPIGON LOTION I as prepared ~n Ex-ample 1 was applied to the lesions and the sub~ects were treated with ultrasound as described above. The blisters were treated on two consecutive days. The active treatment patients reported that itching stopped after 4 to 6 hours. Blisters were reported as having a healing crust after 12 to 18 hours and as disappeared arter about
The medicament is then micromassaged lnto the arrected area by ultrasonic vibrations. For this purpose, an ultrasonlc applicator is slowly moved back and rorth over the leslons, either in a rotary or transverse direction, in order to reduce the concentration of energy at any given point. The pressure applied through the applicator is light but is rirm enough to maintain good coupling. In treating patients having lesions which are particularly pain~ul and sensitive to heat, the ultrasonic applicator, which includes a transducer within an applicator houslng, is preferably water cooled.
The length Or the treatment, output frequency Or the ultrasonic generator coupled to the applicator and power level at the applicator surface will vary in the individual case and is up to the physician. Preferably, however, the output rrequency Or the generator is about 1000 KHZ and the power level at the applicator head is about 1.0 to 3.0 watts per sq. cm~ A suitable ultrasonic generator for this purpose is manufactured by Whitewater Electronics, Inc. and has a 20 _= .. =frequency of 1100 XHZ + 10 KHZ, a continuous power output Or 0 to 32 watts and an erfective power level at the applicator head Or 3.0 watts per sq. cm.
The rrequency and number Or treatments is deter-mined individually at the discretion Or the physician. Orten to begin with, treatments are given daily ~or 2 to 3 minutes and then reduced in rrequency when desired efrects are ob-tained. It is not unusual, however~ that only one treatment is necessary berore beneficial efrects become a~parent.
The rollowing examples illustrate the invention~
: ~ _ 9 _ ~ .
~ 3~ ~
An e~recti~e medicament (HERPIGON LOTION I) ror the treatment Or Herpes Slmplex Type 1 lesions by ultra-sound was prepared by blending the following materials:
.
In~redient Percent by Weight Urea . 3 Zinc oxide 2 Tannic acid Menthol .5 HEB cream 66 Ethyl alcohol . qs .
EXAMPLE Z
.To demonstrate that ultrasonic vibrations cause HERPIGON LOTION I to penetrate tissues through the skin, sixty rats were chosen, their backs shaved and treated as rOllOws: - -: Ten rats were selected ~or each o~ three tests in Group A. In each tes~, radioactive HERPIGON LOTION I
was rubbed onto the shaved backs o~ the rats. As shown in Table A, in Test 1 the radioactive component o~ the HERPIGON
LOTION I was tannic acid, ln Test ~ it was urea and in Test 3 it was a combination Or tannic acid and ureaO Otherwlse9 the HERPIGON LOTION I used in these tests was prepared as in Example 1~
' TABLE A
Rad~oactive Component Test 1, Test 4 Tannic acid (H3) Test 2, Test 5 Urea (C14) Test 3, Test 6 Tannic acid (H3) and Urea (C14 . . .
~ j l ~33~D4~
Ten rats were selected for each o~ three tests in Group B. In each test, radioactive HERPIGON LOTION I
was rubbed ~nto the shaved backs o~ the rats and micro-massaged therein with ultrasound ror about 5 minukes. An ultrasonlc generator with a f'requency of 1100 KHZ ~ 10KHZ -was coupled to an ultrasonic applicator. The applicator head measured 2.5 sq. cm. and had an efrectlve power level of 1 watt per sq. cm. As shown in Table A, the radioactive components of the HERPIGON LOTION I in Tests 4, 5 and 6 were the same as in Tests 1, 2 and 3, respectively.
All Or the rats in Groups A and B were sacrificed and vertical sections 1 inch thick including the skin were taken rrom their back muscles. Slices were then made, ~ixed ; and analyzed by autoradiographic localization ror penetration Or the radioactive drugs. The results show that both radio-- active urea and tannic acid are caused to enter the muscle _to a depth Or from about 1/2 inch to about 1 inch when they are applled with ultrasonic vibrations. When they are ap-plied without vibrations, they remain on the surface o~ the skin and do not penetrate the muscle.
Ten sub~ects su~fering oral herpes were chosen on the basis Or visible evidence of active lesions on the lips, inside Or the lips or mouth. Each had 3 or 4 vesicles and came in for treatment between 12 and 24 hours after appearance of the blisters. A sample was taken by cotton swab rrom the inrected area Or each sub~ect and preserved in a special media for virus culture. The virus h~as identified as Herpes Simplex ; 3o Type 1 by culture and by electron microscopy.
Five of the subJects were selected for a control group. They were treated by rubblng an ultrasonic applicator ;
r ~3~
head as described in Example 2 over the infected area for two minutes~ The control patients reported that itching continued ror 4 to 7 days and that the blisters took rrom 7 to 12 days to disappear.
me other five sub~ects were selected for an active treatment group acsording to the present lnvent-ionO An amount o~ HERPIGON LOTION I as prepared ~n Ex-ample 1 was applied to the lesions and the sub~ects were treated with ultrasound as described above. The blisters were treated on two consecutive days. The active treatment patients reported that itching stopped after 4 to 6 hours. Blisters were reported as having a healing crust after 12 to 18 hours and as disappeared arter about
4 days.
An effective medicament (HERPIGON LOTION II3 .. .. .
for the treatment of Herpes Simplex Type 2 lesions by ultrasound was prepared by blending the following mater-~; 20 ials: `
IngredientPercent by Weight Urea 3 Zinc oxide 3 Tannic ac~d 2 HEB cream 65 , ' EXAI~PLE 5 Twenty female subJects sufrering from recurrent geni~al herpes at least three tlmes in the preceding year were chosen. Each patient came in for treatment about 12 ~83~
- to 24 hours a~ter appearance o~ the blisters as veslcles on the vulva and orirlce Or the vaglna. A sample was taken by cotton swab from the infected area of each subJect both be~ore and after treatment and preserved in a speclal medla for virus culture. The virus was ident~fied as Herpes Simplex Type 2 by culture and by electron microscopy.
Five Or the sub~ects were selected for a control group. Members of this group had 20 to 50 blisters and were treated by rubbing an ultrasonic applicator over the infected areas ~or three minutes. The particular applicator selected depended on the size Or the infected area. Probe A measured 5 sq . cm., Probe B 2.5 sq . cm. and Probe C 1.5 sq. cm. Probe A was used if the blisters covered a wide area. In smaller areas9 Probe B was used and in hidden areas such as beneath the clitorls or labia minora, Probe C was used. The ultrasonic generator coupled to the ap-plicator had an output ~requency of 1100 KHZ ~ 10 KHZ and . .~
the power output was selected so that the e~rective power level a~ the applicator head3 regardless o~ whlch one was selected, was 0 watts per sq. cm~- The control "treatment"
was applied once daily for three consecutive days. The control patients reported that itching and pain lasted ~or about a week to 10 days and that the blisters took 3 to 4 weeks to disappear. All o~ the sub~ects experienced re-current inrections withln three months.
Another five sub~ects were selected as a group for treatment with ultrasound alone. Members o~ this group had 7 to 50 vesicular lesions and were treated as de-scrlbed above except that the power level at the applicator head , .
was 1 watt per sq. cm.~ once daily ror three consecutlve days~ On the third day Or treatment 3 60 percent Or the vlrus had been killed ~s evidenced by the sample taken on the cotton swab. The ultrasound treatment group re-ported that itching and pain lasted about 4 days and that the bllsters disappeared after about 18 to 20 days.
Five more of the sub~ects were selected for treatment with HERPIGON LOTION II alon~. Members o~ this group had 10 to 50 vesicular lesions and were treated by rubbing HERPIGON LOTION II onto the infected areas twice a day for three daysO On the third day Or treatment, 65 percent of the virus had been killed. The HERPIGON LOTION
II treatment group reported that itching lasted about 3 days and that the blisters disappeared after about 15 to 17 days.
The other five subJects were treated as follows.
, = = ~ .
Members of this group had 10 to 50 vesicular lesions and . _ . . . .......... . .
were treated by rubbing HERPIGON LOTION II onto the infected areas and immediately micromassaging it therein with the ~20 probes described for the con~rol group except that the power-level at the applicator head was 1 watt per sq. cm. This treatment was applied once daily for three minutes on each o~
three consecutive days. On the third day of treatment~ 100 percent Or the vlrus had been killed at the site Or the lesions. This treatment group reported itching stopped after 12 to 24 hours and blister disappearance after 5 to - -7 days.
All t~enty sub~ects were followed after treatment, As ~entioned above, all of the control group had recurrent ; :
.
- 14 - , .
.
3~
genital herpes ln~ections wlthin three monthsr ~i~ty percent o~ the subJects treated with ultrasound alone had.
recurrent lnfections within 5 months, 45 percent o~ the sub~ects treated with HERPIGON LOTION II alone had recur-rent infections within 6 months but 100 percent Or the sub~ects treated with HERPIGON LOTION II and ultrasound were stlll ~ree ~rom recurrent infections after one year.
Ten male sub~ects suf~ering genital herpes were o chosen. Each had 2 to 6 vesicles on the glans o~ the penis or on the penis. No bllsters were noted on the scrotum with the exception of one patient who had two blisters.. A sample - .
was taken by cotton swab from the inrected areas Or each~
; sub~ect and preserved in a special media ~or virus culture.
; The virus was identified as Herpes Simplex Typë II by cul-ture and by electron microscopy.
- Five of the sub~ects were selected-for a control~~
group. They were treated by rubbing an ultrasonic applicator ~ L; :. head such as Probe A or Probe B o~ Example 4 over.the in-. ~r~
0 ~ected areas for three minutes. The power level~at the-:--~--- ----applicator head was set for O watts per sq. cm. The control patlents seldom reported itching but those who did said that lt lasted about 3 days. Blisters took 2 weeks to dis-appear. : .
The other rlve sub~ects were selected--ror an actlve treatment group according to the present invention~ An amount Or HERPIGON LOTION II was applied to the lesions and the sub~ects were treated as described for the control group aboYe except that the effective power level at the appli-3 cator head was 1 watt per sq. cm. These patients reported .
.
' :
3~
that itching (if initially pr~ opp~d within 4 ko 8 hours and that the blisters disappeared within 5 to 7 days, An effective medicament (DEMIDOX SHAMPOO~ for the treatment o~ demidox mites in dogs when applied with ultrasound was prepared by blending the following mater-ials~
In~redient Percent by Weight Urea 20 : ' Dimethyl sulfoxide 10 C:lyFerol ' qs '' ,',,,,, ,,,,,, ,,, ~, - In general~ effective DEMIDOX SHAMPOOS conta~n =~. .. .
rrom about 10 to about 50 percent by weight of urea and from about 1 to about 20 percent by weight. of-dimethyl. ..... _ .
-., ........ sulfoxide with the balance being made up by gly.cerol. _ l~en these shampoos are micromassaged into the infected ... areas with ultrasound as described for treatment.o~ Herpes - - . ~
- - Simplex Type 1 or 2 lesions, the urea.and.dime~hy.l.,,sul-..~
2~ foxide penetrate the tissues ancl kill the mite e&gs. The ; glycerol acts as an ultrasound coupling agent and as a lubricant.
. ' .
Seven dogs suffering with demidox were treated--''' by rubbing an ~mount Or DEMIDOX SHAMPOO as prepared in ~-Example 7 onto the infected areas. These areas were then rubbed with an ultrasonic applicator for 5 to 7 minutes.
An ultrasonic generator as described in Example 2 was '`, ' `,.
.
.~ '".
set so that the efrectlve power level at the appllcator head was rrom about 1 to about 1.5 watts per sq. cm. The dogs were treated every other day ror 20 days. All seven Or the dogs were cured after 10 treatments.
In view Or the above~ lt will be seen that the several ob~ects Or the inventlon are achieved and other advantageous results attainedO
As various changes could be made in the above methods and compositions wlthout departing rrom the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.
An effective medicament (HERPIGON LOTION II3 .. .. .
for the treatment of Herpes Simplex Type 2 lesions by ultrasound was prepared by blending the following mater-~; 20 ials: `
IngredientPercent by Weight Urea 3 Zinc oxide 3 Tannic ac~d 2 HEB cream 65 , ' EXAI~PLE 5 Twenty female subJects sufrering from recurrent geni~al herpes at least three tlmes in the preceding year were chosen. Each patient came in for treatment about 12 ~83~
- to 24 hours a~ter appearance o~ the blisters as veslcles on the vulva and orirlce Or the vaglna. A sample was taken by cotton swab from the infected area of each subJect both be~ore and after treatment and preserved in a speclal medla for virus culture. The virus was ident~fied as Herpes Simplex Type 2 by culture and by electron microscopy.
Five Or the sub~ects were selected for a control group. Members of this group had 20 to 50 blisters and were treated by rubbing an ultrasonic applicator over the infected areas ~or three minutes. The particular applicator selected depended on the size Or the infected area. Probe A measured 5 sq . cm., Probe B 2.5 sq . cm. and Probe C 1.5 sq. cm. Probe A was used if the blisters covered a wide area. In smaller areas9 Probe B was used and in hidden areas such as beneath the clitorls or labia minora, Probe C was used. The ultrasonic generator coupled to the ap-plicator had an output ~requency of 1100 KHZ ~ 10 KHZ and . .~
the power output was selected so that the e~rective power level a~ the applicator head3 regardless o~ whlch one was selected, was 0 watts per sq. cm~- The control "treatment"
was applied once daily for three consecutive days. The control patients reported that itching and pain lasted ~or about a week to 10 days and that the blisters took 3 to 4 weeks to disappear. All o~ the sub~ects experienced re-current inrections withln three months.
Another five sub~ects were selected as a group for treatment with ultrasound alone. Members o~ this group had 7 to 50 vesicular lesions and were treated as de-scrlbed above except that the power level at the applicator head , .
was 1 watt per sq. cm.~ once daily ror three consecutlve days~ On the third day Or treatment 3 60 percent Or the vlrus had been killed ~s evidenced by the sample taken on the cotton swab. The ultrasound treatment group re-ported that itching and pain lasted about 4 days and that the bllsters disappeared after about 18 to 20 days.
Five more of the sub~ects were selected for treatment with HERPIGON LOTION II alon~. Members o~ this group had 10 to 50 vesicular lesions and were treated by rubbing HERPIGON LOTION II onto the infected areas twice a day for three daysO On the third day Or treatment, 65 percent of the virus had been killed. The HERPIGON LOTION
II treatment group reported that itching lasted about 3 days and that the blisters disappeared after about 15 to 17 days.
The other five subJects were treated as follows.
, = = ~ .
Members of this group had 10 to 50 vesicular lesions and . _ . . . .......... . .
were treated by rubbing HERPIGON LOTION II onto the infected areas and immediately micromassaging it therein with the ~20 probes described for the con~rol group except that the power-level at the applicator head was 1 watt per sq. cm. This treatment was applied once daily for three minutes on each o~
three consecutive days. On the third day of treatment~ 100 percent Or the vlrus had been killed at the site Or the lesions. This treatment group reported itching stopped after 12 to 24 hours and blister disappearance after 5 to - -7 days.
All t~enty sub~ects were followed after treatment, As ~entioned above, all of the control group had recurrent ; :
.
- 14 - , .
.
3~
genital herpes ln~ections wlthin three monthsr ~i~ty percent o~ the subJects treated with ultrasound alone had.
recurrent lnfections within 5 months, 45 percent o~ the sub~ects treated with HERPIGON LOTION II alone had recur-rent infections within 6 months but 100 percent Or the sub~ects treated with HERPIGON LOTION II and ultrasound were stlll ~ree ~rom recurrent infections after one year.
Ten male sub~ects suf~ering genital herpes were o chosen. Each had 2 to 6 vesicles on the glans o~ the penis or on the penis. No bllsters were noted on the scrotum with the exception of one patient who had two blisters.. A sample - .
was taken by cotton swab from the inrected areas Or each~
; sub~ect and preserved in a special media ~or virus culture.
; The virus was identified as Herpes Simplex Typë II by cul-ture and by electron microscopy.
- Five of the sub~ects were selected-for a control~~
group. They were treated by rubbing an ultrasonic applicator ~ L; :. head such as Probe A or Probe B o~ Example 4 over.the in-. ~r~
0 ~ected areas for three minutes. The power level~at the-:--~--- ----applicator head was set for O watts per sq. cm. The control patlents seldom reported itching but those who did said that lt lasted about 3 days. Blisters took 2 weeks to dis-appear. : .
The other rlve sub~ects were selected--ror an actlve treatment group according to the present invention~ An amount Or HERPIGON LOTION II was applied to the lesions and the sub~ects were treated as described for the control group aboYe except that the effective power level at the appli-3 cator head was 1 watt per sq. cm. These patients reported .
.
' :
3~
that itching (if initially pr~ opp~d within 4 ko 8 hours and that the blisters disappeared within 5 to 7 days, An effective medicament (DEMIDOX SHAMPOO~ for the treatment o~ demidox mites in dogs when applied with ultrasound was prepared by blending the following mater-ials~
In~redient Percent by Weight Urea 20 : ' Dimethyl sulfoxide 10 C:lyFerol ' qs '' ,',,,,, ,,,,,, ,,, ~, - In general~ effective DEMIDOX SHAMPOOS conta~n =~. .. .
rrom about 10 to about 50 percent by weight of urea and from about 1 to about 20 percent by weight. of-dimethyl. ..... _ .
-., ........ sulfoxide with the balance being made up by gly.cerol. _ l~en these shampoos are micromassaged into the infected ... areas with ultrasound as described for treatment.o~ Herpes - - . ~
- - Simplex Type 1 or 2 lesions, the urea.and.dime~hy.l.,,sul-..~
2~ foxide penetrate the tissues ancl kill the mite e&gs. The ; glycerol acts as an ultrasound coupling agent and as a lubricant.
. ' .
Seven dogs suffering with demidox were treated--''' by rubbing an ~mount Or DEMIDOX SHAMPOO as prepared in ~-Example 7 onto the infected areas. These areas were then rubbed with an ultrasonic applicator for 5 to 7 minutes.
An ultrasonic generator as described in Example 2 was '`, ' `,.
.
.~ '".
set so that the efrectlve power level at the appllcator head was rrom about 1 to about 1.5 watts per sq. cm. The dogs were treated every other day ror 20 days. All seven Or the dogs were cured after 10 treatments.
In view Or the above~ lt will be seen that the several ob~ects Or the inventlon are achieved and other advantageous results attainedO
As various changes could be made in the above methods and compositions wlthout departing rrom the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.
Claims (9)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS
:
1. An effective antiviral medication for treatment of Herpes Simplex lesions comprising urea and a physiologically acceptable zinc compound in an oil coupling agent, the urea and the zinc compound being present in an effective amount.
2. The effective antiviral medication for treatment of Herpes Simplex lesions according to claim 1 wherein the urea is present in an amount from about 5 to about 40 percent by weight.
3. The effective antiviral medication for treatment of Herpes Simplex lesions according to claim 2 wherein said lesions are Type 1 lesions and wherein the urea is present in an amount from about 10 percent to about 40 percent by weight.
4. The effective antiviral medication for treatment of Herpes Simplex Type 1 lesions according to claim 3 which further includes tannic acid in an effective amount.
5. The effective antiviral medication for treatment of Herpes Simplex Type 1 lesions according to claim 4 wherein the zinc com-pound is zinc oxide and is present in an amount from about 0.5 percent to about 3 percent by weight and wherein the tannic acid is present in an amount from about 0.5 percent to about 2 percent by weight.
6. The effective antiviral medication for treatment of Herpes Simplex Type 1 lesions according to claim 5 which further includes menthol in an amount from about 0.25 percent to about 1 percent by weight, ethyl alcohol in an amount from about 0.30 percent to about 1.0 percent by weight and the oil coupling agent is present in an amount from about 65 percent to about 70 percent by weight.
7. The effective antiviral medication for treatment of Herpes Simplex lesions according to claim 2 wherein said lesions are Type 2 lesions and wherein the urea is present in an amount from about 10 percent to about 40 percent by weight.
8. The effective antiviral medication for treatment of Herpes Simplex Type 2 lesions according to claim 7 which further includes tannic acid in an effective amount.
9. The effective antiviral medication for treatment of Herpes Simplex Type 2 lesions according to claim 8 wherein the zinc compound is zinc oxide and is present in an amount from about 1 percent to about 5 percent by weight, wherein the tannic acid is present in an amount from about 1 percent to about 5 percent by weight and wherein the oil coupling agent is present in an amount from about 60 to about 70 percent by weight.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65614376A | 1976-02-09 | 1976-02-09 | |
| US656,143 | 1976-02-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1083040A true CA1083040A (en) | 1980-08-05 |
Family
ID=24631816
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA271,202A Expired CA1083040A (en) | 1976-02-09 | 1977-02-07 | Topical application of medication by ultrasound with coupling agent |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS52115591A (en) |
| CA (1) | CA1083040A (en) |
| GB (1) | GB1577551A (en) |
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| US4767402A (en) * | 1986-07-08 | 1988-08-30 | Massachusetts Institute Of Technology | Ultrasound enhancement of transdermal drug delivery |
| JPS63135179A (en) * | 1986-11-26 | 1988-06-07 | 立花 俊郎 | Subcataneous drug administration set |
| JPH074428B2 (en) * | 1989-07-31 | 1995-01-25 | 俊郎 立花 | Ultrasonic drug administration device |
| US5115805A (en) * | 1990-02-23 | 1992-05-26 | Cygnus Therapeutic Systems | Ultrasound-enhanced delivery of materials into and through the skin |
| CA2063529A1 (en) | 1991-03-22 | 1992-09-23 | Katsuro Tachibana | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
| US5814599A (en) * | 1995-08-04 | 1998-09-29 | Massachusetts Insitiute Of Technology | Transdermal delivery of encapsulated drugs |
| US6041253A (en) * | 1995-12-18 | 2000-03-21 | Massachusetts Institute Of Technology | Effect of electric field and ultrasound for transdermal drug delivery |
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-
1977
- 1977-02-07 CA CA271,202A patent/CA1083040A/en not_active Expired
- 1977-02-07 GB GB495477A patent/GB1577551A/en not_active Expired
- 1977-02-09 JP JP1346277A patent/JPS52115591A/en active Pending
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Also Published As
| Publication number | Publication date |
|---|---|
| JPS52115591A (en) | 1977-09-28 |
| GB1577551A (en) | 1980-10-22 |
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