CA1169774A - Medication having penetration through cutaneous surfaces into articular and muscular areas - Google Patents
Medication having penetration through cutaneous surfaces into articular and muscular areasInfo
- Publication number
- CA1169774A CA1169774A CA000375605A CA375605A CA1169774A CA 1169774 A CA1169774 A CA 1169774A CA 000375605 A CA000375605 A CA 000375605A CA 375605 A CA375605 A CA 375605A CA 1169774 A CA1169774 A CA 1169774A
- Authority
- CA
- Canada
- Prior art keywords
- parts
- therapeutic composition
- composition according
- further characterized
- glucocorticoidal
- 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.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- A61K38/35—Corticotropin [ACTH]
Abstract
MEDICATION HAVING PENETRATION THROUGH
CUTANEOUS SURFACES INTO ARTICULAR
AND MUSCULAR AREAS
ABSTRACT OF THE DISCLOSURE
A medication that penetrates the surface of the skin is provided. The articular and muscular areas subject to discomfort may be re-lieved by the topical application of the medi-cation. The medication has a penetrant of di-methyl sulfoxide, an anti-inflammatory agent, made from glucocorticoids, and a topical anes-thetic compound. The medication greatly relieves pain and reduces swelling.
CUTANEOUS SURFACES INTO ARTICULAR
AND MUSCULAR AREAS
ABSTRACT OF THE DISCLOSURE
A medication that penetrates the surface of the skin is provided. The articular and muscular areas subject to discomfort may be re-lieved by the topical application of the medi-cation. The medication has a penetrant of di-methyl sulfoxide, an anti-inflammatory agent, made from glucocorticoids, and a topical anes-thetic compound. The medication greatly relieves pain and reduces swelling.
Description
~7~
1, MEDICATION HAVING P~NETRATION TH~OUGH
- CUTANEOUS SURFACES INTO ARTICULAR
_ `~ND MUSCULAR ARE~S
TECHNICAL FIELD
This invention relates to a therapeutic composition for the relief of intra-articular and intra muscular discomfor~ and the method for application of that therapeutic composition to cutaneous surfaces.
BACKGROUND ART
Treatment of discom~ort in intra-muscular and intra-artlcular areas has typically involved medications injected beneath the cutaneous surface or oral administration. Use of the blood stream to carry the medication to the discomforted area may sometimes cause undesirable side effects to areas not desired for treatment. Further, the ~s delay of transmission of the medication into the blood stream is not conducive to rapid relief.
Injection of medications directly into a joint may cause recrystallization of the medication wi~hin the joint, causing synovitis.
A direct penetration of an active ingredi-ent medication involves percutaneous administrat-ion of the medication. The use of lower aliphatic sulfo~ide~ in slight concentrations has been ~.
recorded in the prior art. The ~ollowing table ~' indIcates those United States patents where the concentration o the lower aliphatic sulfoxide is less than 25 percent.
1, MEDICATION HAVING P~NETRATION TH~OUGH
- CUTANEOUS SURFACES INTO ARTICULAR
_ `~ND MUSCULAR ARE~S
TECHNICAL FIELD
This invention relates to a therapeutic composition for the relief of intra-articular and intra muscular discomfor~ and the method for application of that therapeutic composition to cutaneous surfaces.
BACKGROUND ART
Treatment of discom~ort in intra-muscular and intra-artlcular areas has typically involved medications injected beneath the cutaneous surface or oral administration. Use of the blood stream to carry the medication to the discomforted area may sometimes cause undesirable side effects to areas not desired for treatment. Further, the ~s delay of transmission of the medication into the blood stream is not conducive to rapid relief.
Injection of medications directly into a joint may cause recrystallization of the medication wi~hin the joint, causing synovitis.
A direct penetration of an active ingredi-ent medication involves percutaneous administrat-ion of the medication. The use of lower aliphatic sulfo~ide~ in slight concentrations has been ~.
recorded in the prior art. The ~ollowing table ~' indIcates those United States patents where the concentration o the lower aliphatic sulfoxide is less than 25 percent.
2.
3,981,9g6~,148,gl7 4,148,874 3,592,9304,14~,887 3,952,099 3j888 ! 995 3,896,238 4,046,886
4,130,6674,148,893 3,953,599 4,148,924 The prior art also discloses compositions where the lower aliphatic sulfoxide comprises greater than 50 percent of the overall composi~
tion. Table 2 illustrates the United States patents indicating this majority composition ingredient.
TABLE ~
3;551,554 3,743,727 3,77I,606 3,771,602 3,592,93 The use of lower aliphatic sulfoxide has been criticized, particularly dimethyl sulfoxide.
United States Patent Nos. 3,527,864; 3,903,256;
and 3,678J156 all teach the preferred use of higher aliphatic sulfoxides. Indeed, some percutaneous penetrant systems emphasize the avoidance of lower aliphatic sulfoxides, to wit:.United States fi;!, Patents Nos, 4,032,661; 4,070,449; and 3,326,768. '-Dimethyl sulfoxide was regarded as an active ingredient in United States Patents Nos.
.
3~
3,740,420 and 3,790,676~ Further, United States Patent No. 3,321,364 teaches t~e use vf dimethyl sulfoxide as a.foliage insecticide, while United States Patent No. 3,527,863 ~eaches ~he use of dimethyl sulfoxide as a preservative in tissue sectioning.
The us e of a percutaneous penetran~
system where the lower aliphatic sulfoxide is less than 25 percent is not adequate to penetrate tis-sues having a higher density concentration. Con-trariwise, percutaneous penetrant systems where the lower aliphatic sulfoxide exceeds S0 percent, have been found to cause significant adverse reactions or systems unjustifiedly relying upon the alleged miraculous quali~ies of the pene~rant itself, rather than the active ingredient. When treating intra-muscular and intra-articular discomfort, a signi-ficant balance must be obtained between the con- '.,5 centration of the penetrant serving as the carrier and the anti-inflammatory agent being transported by the carrier percutaneously. I'herefore, the neea exists for a the~apeutic composition which has suf-ficient penetrant to rapidly carry the activ~
anti-inflammatory agent percutaneously, while not exceeding such concentrations as to mask and di-minish the effectiveness of ~hose anti-inflammatory agents. The need further exists to distinguish the proper use of lower aliphatic sulfoxides as .::
a cutaneous penetrant, rather than serving as an active ingredient in the system. ..
7 ;~9~
DISCLOSURE OF INVENTION
Therefore, it is an aspect of -the invention to provide a therapeutic composition for the relief of intra-articular and intra-muscular discom~ort, where-in the penetrant concentration exceeds 25 percent, but remains less than 50 percent of the total concen-tration of the composition.
Another aspect of the invention is to provide a therapeutic composition for the relief of intra-articular and intra-muscular discomfort, wherein the penetrant serves in an absorbent carrier function for physiologically active glucocorticoidal agents.
It is another aspect of the invention to pro-vide a therapeutic composition, as above, wherein a topical anesthetic compound is applied to the cutaneous surface for the diminished sensory recognition of dis-comfort within the articular and the muscular areas.
Still another aspect of the invention is to provide a method for the treatment of intra-articular and intra-muscular discomfort wherein a therapeutic composition, as above, is supplied to the cutaneous surface of the affected area.
Moreover, it is an aspect of the invention to provide a method for the treatment of intra-articular and intra-muscular discomfort, as above, wherein the therapeutic composition reduces inflammation of the discomforted areas.
It is yet another aspect of the invention to provide a therapeutic composition and a method for application of the same, as above, wherein the relief is administered percutaneously for direct, controlled, and immediate relief.
These aspects and other aspects of the inven-tion which will become apparent as the detailed descrip-tion of the best mode for carrying out the invention ~ ~ .
.
, `7~
proceeds, are achie~ed b~: a therapeu-tic composition for the relief of intra-articular and intra-muscular discomfort beneath cutaneous surfaces, comprising:
(a) from about 25 to less than 50 parts by weight of a percutaneous penetrant selected from sulfoxides hav-int the following formula:
R - S -R' Il o where R and R' are aliphatic hydrocarbon radicals hav-ing from 1 to 5 carbon atoms and may be the same group;
(b) from about 0.25 to about 0.75 parts by weight of a topical anesthetic compound; and (c) from about 0.005 to about 0.10 parts by weight of at least one physio-logically active glucocorticoidal agent selected from the grou.p consisting of: adrenocoricotropin hormone (ACTH), cortisone, hydrocortisone, prednisone, prednis-olone, triaminolone, methyl prednisolone, meprednisone, paramethasone, fluprednisolone, dexamethasone, and betamethasone.
The aspects of the invention are also achieved by a method for the treatment of intra~articular and intra-muscular discomfort beneath a cutaneous surface, comprising: (a) heating the cutaneous surface over the discomforted intra-articular and intra-muscular areas for a few minutes; (b) applying a topical appli-cation of a therapeutic composition into said cutane-ous surface; said therapeutic composition comprising:
(a) from about 25 to about 50 parts of a percutaneous penetrant selected from sulfoxides having the follow-ing formula:
R- S - R' `11 o where R and R' are aliphatic hydrocarbon radicals hav-ing from 1 to 5 carbon atoms and may be the same radical;
.
(b) from about 0.25 to about 0.75 parts of a topical anesthetic compound; and (c) from about 0.005 to about 0.10 parts of at least one physiologically active glu-cocorticoidal agent selected from the group consist-ing of adrenocorticotropin hormone (ACTH), cortisone, hydrocortisone, prednisone, prednisolone, triamino-lone, methyl prednisolone, meprednisone, parametha-sone, fluprednisolone, dexamethasone, and betametha-sone.
BEST MODE FOR CAR~YING OUT THE INVENTION
The use of lower aliphatic sulfoxides, and particularly dimethyl sulfoxide, as a therapeutic agent or carrier for other therapeutic agents has been repeatedly examined by the United States Food and Drug Administration. Claims that the dimethyl sulfoxide (DMSO) serves as a thera-peutic agent for the relief of pain are publicly announced without specific approval by that Federal agency and amidst scientific controversy. Advocates discussing the use of DMSO as a penetrant carrier for other chemicals are divided in~o two specific schools of thought: those which advocate the use of the pene-trant in concentrations less than 25 percent of the total composition, and those which advocate the concen-tration greater than 50 percent of the total composi-tion. It has been found by this inventor that the optim-al percentage of lower aliphatic sulfoxides to be used as a penetrant and carrier for other active ingredients is between the range of 25 percent and 50 percent of the total composition of the therapeutic compound.
Whenever a concentration greater than 50 percent is employed using a lower aliphatic 6~7~
sulfoxide, and part'icularly DMSO, ~he patien~
experiences a side reaction of a garlic taste in the oral cavi,ty. A test with a percentage of DMSO
greater than 50'percent has indicated that the therapeutic action of the composition is not en-hanced while the'concentration of ~he ~MSO is needlessly high.
Whenever t~e concentration of the lower aliphatic sulfoxide, and particularly DMSO, is less than 25 percent of the total composition, it has been found that the penetrating capabilities of the entire therapeutlc composition is less effective than desired for high-density intra-muscular and intra-articular areas. Consequently, the preferred range has been found ~o be between 25 percent and 50 percent of the total therapeutic composition.
Relief of intra~uscular and intra- ..
articular discomfort must gensrally employ an anti-inflamm~tory agent ~o relieve pain and swel-ling of the discomforted areas. Once again, it has been found that these anti-inflammatory agents are most effective when ~he concentration of the lower aliphatic sulfoxide is between 25 and 50 percent of the total composition~ The therapeutic compositlon may utilize any number of anti-inflamma-tory agents or any combinations of anti-inflammatory agents sufficient to satisfy the particular arti- , cular or muscular treatment desired. '' The use of anti-infla~matory agents through injection into the joint has been found to be detri-mental to the therapy sought. Injections of anti-~ r~, inflammatory agents ~ay, within the Join~, recrysta-lize causing synovitis. Percutaneous penetration does not lead to recrystalization o~ the anti-in1ammatory agen~.
The anti-inflammatory agents of the present invention are classified as physiologically active glucocorticoidal agents, those adrenal cortical steroids which serve to reduce inflam-mation. In the present invention, it has been found that a percentage from about 0.005 to about 0.10 percent o~ the total therapeutic composition should comprise at least one physiologically active glucocorticoidal agent. Preferably, the concen-tra~ion is about 0.025 percent of the total thera-peutic composition.
Physiologically active glucocorticoidal a~en~s include the following natural and synthesized steroids: adrenocorticotropin hormone (ACTH), cortisone, hydrocortisone, prednisone, prednis-2Q olone, triaminolone, methyl prednisolone, mepred-nisone, paramethasone, fluprednisolone, dexametha-sone, and betamethasone. Refinement of the parti-cular glucocorticoidal agent to be used with the treatment of a speciic articular or intra-muscular discomfort depends upon the discomfort involved.
Glucocorticoidal agents are commonly employed for various rheumatic conditions, including, post-traumatic osteoarthritis, synovitis o~ osteoarthri-tis, rheumatoid arthritis, acute and subacute bur-sitis, epicondylitis~ acute nonspécific tenosyno-vitis, acute gouty arthritis, psoriatic arthritis, and ankylosing spondylitis. Typical collagen 7 ~
. ~.
di.seases which glucocorticoidal agents are employed inlude systemic lupus erythemoatosu5, sy8temic dermatomysitis, and acute rheumatic carditis.
These anti-inflammatory agents prevent damage to joint colla~en and bone tissues as caused by abnormal production of collagenase and enzymes in the synovi.al fluid. Synovial cells release la-tent colla~enase which remains latent unless acti-~ated by an actîve enzyme. Rheumato~ cells con-verts inactive plasminogen into active plasminenzyme~ This latter enzyme activates the latent collagenase into active collagenase, which when in th.e synoYial fluid, attacks ~he adjacent col-lagen and bone tissues during joint movement. The anti-inflamma~ory agents, even in a low concentration, inhibit the production of plasminogenand the con-verting substance in the rheumatoid cells, thereby main~aining collagenase in its latent form~ These anti-inflammatory agents also assist in maintain-ing the immune processes within the joints them-selves.
In addition to the lower aliphatic sul-foxide and at least one physiologically active glucocorticoidal agent, the therapeutic composition of the present invention also includes from about 0.25 to about 0.75 percent o$ a topical anesthetic compound. The topical a~esthetic compound may include any compound known to those skilled in the ~.
art to anesthetize the cu~aneous ~urface of the patient. Topical anesthetic compounds include lidocaine, tetracaine, di~ucaine, pramoxire HCl, cyclomethycaine sulfate, di~ethisoquine HCL ethyl 10 .
aminobenzoate (benzocaine), lldocaine HC~, diper-odon, butamben picrate, tetracaine HCl, dyclonine HCl, and hexylcaine HCl. The topical anesthetic compound relieves the cutaneous surface of dis-comfort when the therapeutic composition is applied and the physiologically active glucocorticoidal agent and the percutaneous penetrant are percu-taneously absorbed.
The surface area of the skin over the af-fected joint~ bone, or muscle usually have a number of trigger points associated with myofascial and visceral pains. Brief in~ense stimulation of tri~ger points frequently produces prolonged relief of pain~ It is well known that a short-acting local anesthetic stimulates these trigger points to crea~ a prolonged, perhaps permanent, relief from myo~scial and visceral pain. This in~ense stimulation, called hyperstimulation, is necessary in the therapeutic composition of the present in-vention to relieve pain while the glucocorticoidal agents block acti~ation of collagenase. The syner-gistic combination of analgesia and anti-inflammato-ry medication is only possible with cutaneous applica~ion ha~ing percutaneous penetrants therein.
Because of the continuing controversy surrounding the use of lower aliphatic sulfoxides as claimed active ingredients and as known pene-trants, testing of the therapeutic composition of the present invention was conducted under strict control of availability of material. The lower aliphatic sulfoxides o the present invention ;
have the following formula:
11 .
--'S ~ 1,~, O
- where R and R' are aliphatic hydrocarbon radicals having from l to 5 carbon atoms and may be the same radicals. Prefera~ly, the percutaneous pene-trant of the present invention is dimethyl sul-foxide where R and R' are both methyl groups.
The method o,f treatment ~or the intra-articular and intra-muscular discomfor~ of patients comprises heating the cutaneous surface over the discomforted intra-articular and intra-muscular areas for a few minutes with a warm substance, such as a hot towel or other similar method known to those skilled in the art. If moist heat is used, the cutaneous surface should be dried before applying the topical applica~ion of the therapeutic com-position of the present invention onto the cuta-neous surface. This second step should be enhanced by a gentle rubbing of the surface to enhance the functions of the anesthetic compound and to permit penetration of the percutaneous penetrant and the physiologically active glucocorticoidal agent.
This treatment should be repeated daily or more often until the discomort in the articular and mNscular areas subsides.
The percutaneous penetrant, the topical anesthetic compound and at least one physiologi-cally active glucocorticoidal agent may be mixed with a unibase ointment solvent, commonly known to those skilled in the art. This unibase ointment is water soluble and frequently employed as a - substrate within which the active ingredients 7'7~ ~
12.
of any medication ~ay be used. The unibase ointment comprises glycerine, sodium laurel sulate, sodium citrate, and propyl paraben. The penetrant, anes-thetic compound, and glucocorticoidal agents may be mixed directly into about 100 parts of the unibase ointment solvent, such that the sulfoxide penetrant comprises from about ~5 to about 50 parts, the ~opical anesthetic compound comprises from about 0.25 to about 0.75 parts, and the physiologically active glucocorticoidal agent comprises from about 0~005 to about 0~30 ~arts. Preferably, the pene-trant comprise~s 40 parts, the topical anesthetic compound comprises 0.50 parts, and the glucocorti-coidal agent comprises about 0.025 parts of the therapeutic composition. The relative concentra-tions expressed in parts or percentages of these components of the composition do no~ reflect the solvents or solutions in which they are typically commercially available.
2a INDUSTRIAL APPLICABILITY
The administration of a therapeutic compo-sition of the present invention has achieved sig~
nificant utility by reducing conditions of discom-fort resulting from bursitis, arthritis, and other diseases. The following cases demonstrate the unexpected recovery of patients -following treatment with the therapeutic composition of the present invention.
T~e therapeutic composition was prepared according to the following method. Into about 454 grams of unibase ointment was mixed about ,0 . ....... :
7~
192 milliliters of dimethyl sulfoxide 100 percent solution to create about a 40 percent D~SO pene-tration concentration. Next, approximately 48 milliliters of a 5 percent topical cyclaine 501u-tion was added to the unibase composition to create a 0.5 percent concentration of the topical anes-thetic compound. The 5 percent topical Cyclaine*
solution is commercially available from Merck Sharp Dohme, which serves as a trademark for hexylcaine HCl. To that composition was added two physiologi-cally active glucocortiocoidal agents, the first being approximately 2 l/2 milliliters of ACTH
(40 units / 5 ml) or 100 units of ACTH, a commerci-ally available quantity from Parke-Davis Company.
Finally, approximately 48 milliliters of Decadron*
elixir was added to the therapeutic composition as another glucocorticoidal agent. Decadron* elixir is a commercial quantity available from Merck Sharp Dohme, as a trademark for dexamethasone.
Each milliliter of elixir has 0.1 milligrams of dexamethasone, and the therapeutic composition, therefore, contains 0.000105 percent of the total therapeutic composition.
As an equivalent to lO0 units of ACTH, it has been found that approximately 2 1/2 millili-ters of Depomedrol* (40 mg/ml) may be a physiologi-cally active glucocorticoidal agent. Depomedrol*
(40 mg/ml) is a commercially available quantity available from the UpJohn Company as a trademark for methylprednisolone acetate. This Depomedrol* con-tains 40 milligrams of methylprednisolone acetate per milliliter of solution, which creates a con-centration of glucocorticoidal agent of about .~ *Trademark v;;~ r7 4 4 ~
0~022 pereent of the therapeutic composition~
The following cases ~llustrate ~,he direct, controlled, ~nd immediate therapeutic effect o~
the therapeutic compo3ition for patlents having a Yariety of discomforts~
The patien~ is a m~le, aged 59, who has had therapy for several months on his right shoul-der ~mder the care of several doctors with nosignificant improvement, Upon physical examina-tion, the chief complaints are severe pain in the right shoulder with the inability to raise or ex~end the arm~ The pressure point area of the right shoulder is tender upon pressure, and the orthrodiagram shoulder temperature indicates a chronic pain. Laborato~y tests indicate CBC-normal, WBC-normal~ RA factor-ne~ative, BUN ground range blood sugar-no~mal limi~, The ai~gnosis is acute' and chronic bursitis of the right shoulder.
Therapy was begun with the therapeutic composition, (ACTH formulation), used topically to the shoulder area and muscles, Daily treatment included the application of hot towels for five minutes to ~he area, a drying of the area, and the application of the therapeutic composition with a gentle rubbing of the ointment into the skin, After approximately three weeks of daily treatment J ;', pain has left the right shoulder and complete use 30 of the arm~ including raising and rotating the right arm, was obtained without discomfort.
~ .
~ ~`~
37 ~L
tion. Table 2 illustrates the United States patents indicating this majority composition ingredient.
TABLE ~
3;551,554 3,743,727 3,77I,606 3,771,602 3,592,93 The use of lower aliphatic sulfoxide has been criticized, particularly dimethyl sulfoxide.
United States Patent Nos. 3,527,864; 3,903,256;
and 3,678J156 all teach the preferred use of higher aliphatic sulfoxides. Indeed, some percutaneous penetrant systems emphasize the avoidance of lower aliphatic sulfoxides, to wit:.United States fi;!, Patents Nos, 4,032,661; 4,070,449; and 3,326,768. '-Dimethyl sulfoxide was regarded as an active ingredient in United States Patents Nos.
.
3~
3,740,420 and 3,790,676~ Further, United States Patent No. 3,321,364 teaches t~e use vf dimethyl sulfoxide as a.foliage insecticide, while United States Patent No. 3,527,863 ~eaches ~he use of dimethyl sulfoxide as a preservative in tissue sectioning.
The us e of a percutaneous penetran~
system where the lower aliphatic sulfoxide is less than 25 percent is not adequate to penetrate tis-sues having a higher density concentration. Con-trariwise, percutaneous penetrant systems where the lower aliphatic sulfoxide exceeds S0 percent, have been found to cause significant adverse reactions or systems unjustifiedly relying upon the alleged miraculous quali~ies of the pene~rant itself, rather than the active ingredient. When treating intra-muscular and intra-articular discomfort, a signi-ficant balance must be obtained between the con- '.,5 centration of the penetrant serving as the carrier and the anti-inflammatory agent being transported by the carrier percutaneously. I'herefore, the neea exists for a the~apeutic composition which has suf-ficient penetrant to rapidly carry the activ~
anti-inflammatory agent percutaneously, while not exceeding such concentrations as to mask and di-minish the effectiveness of ~hose anti-inflammatory agents. The need further exists to distinguish the proper use of lower aliphatic sulfoxides as .::
a cutaneous penetrant, rather than serving as an active ingredient in the system. ..
7 ;~9~
DISCLOSURE OF INVENTION
Therefore, it is an aspect of -the invention to provide a therapeutic composition for the relief of intra-articular and intra-muscular discom~ort, where-in the penetrant concentration exceeds 25 percent, but remains less than 50 percent of the total concen-tration of the composition.
Another aspect of the invention is to provide a therapeutic composition for the relief of intra-articular and intra-muscular discomfort, wherein the penetrant serves in an absorbent carrier function for physiologically active glucocorticoidal agents.
It is another aspect of the invention to pro-vide a therapeutic composition, as above, wherein a topical anesthetic compound is applied to the cutaneous surface for the diminished sensory recognition of dis-comfort within the articular and the muscular areas.
Still another aspect of the invention is to provide a method for the treatment of intra-articular and intra-muscular discomfort wherein a therapeutic composition, as above, is supplied to the cutaneous surface of the affected area.
Moreover, it is an aspect of the invention to provide a method for the treatment of intra-articular and intra-muscular discomfort, as above, wherein the therapeutic composition reduces inflammation of the discomforted areas.
It is yet another aspect of the invention to provide a therapeutic composition and a method for application of the same, as above, wherein the relief is administered percutaneously for direct, controlled, and immediate relief.
These aspects and other aspects of the inven-tion which will become apparent as the detailed descrip-tion of the best mode for carrying out the invention ~ ~ .
.
, `7~
proceeds, are achie~ed b~: a therapeu-tic composition for the relief of intra-articular and intra-muscular discomfort beneath cutaneous surfaces, comprising:
(a) from about 25 to less than 50 parts by weight of a percutaneous penetrant selected from sulfoxides hav-int the following formula:
R - S -R' Il o where R and R' are aliphatic hydrocarbon radicals hav-ing from 1 to 5 carbon atoms and may be the same group;
(b) from about 0.25 to about 0.75 parts by weight of a topical anesthetic compound; and (c) from about 0.005 to about 0.10 parts by weight of at least one physio-logically active glucocorticoidal agent selected from the grou.p consisting of: adrenocoricotropin hormone (ACTH), cortisone, hydrocortisone, prednisone, prednis-olone, triaminolone, methyl prednisolone, meprednisone, paramethasone, fluprednisolone, dexamethasone, and betamethasone.
The aspects of the invention are also achieved by a method for the treatment of intra~articular and intra-muscular discomfort beneath a cutaneous surface, comprising: (a) heating the cutaneous surface over the discomforted intra-articular and intra-muscular areas for a few minutes; (b) applying a topical appli-cation of a therapeutic composition into said cutane-ous surface; said therapeutic composition comprising:
(a) from about 25 to about 50 parts of a percutaneous penetrant selected from sulfoxides having the follow-ing formula:
R- S - R' `11 o where R and R' are aliphatic hydrocarbon radicals hav-ing from 1 to 5 carbon atoms and may be the same radical;
.
(b) from about 0.25 to about 0.75 parts of a topical anesthetic compound; and (c) from about 0.005 to about 0.10 parts of at least one physiologically active glu-cocorticoidal agent selected from the group consist-ing of adrenocorticotropin hormone (ACTH), cortisone, hydrocortisone, prednisone, prednisolone, triamino-lone, methyl prednisolone, meprednisone, parametha-sone, fluprednisolone, dexamethasone, and betametha-sone.
BEST MODE FOR CAR~YING OUT THE INVENTION
The use of lower aliphatic sulfoxides, and particularly dimethyl sulfoxide, as a therapeutic agent or carrier for other therapeutic agents has been repeatedly examined by the United States Food and Drug Administration. Claims that the dimethyl sulfoxide (DMSO) serves as a thera-peutic agent for the relief of pain are publicly announced without specific approval by that Federal agency and amidst scientific controversy. Advocates discussing the use of DMSO as a penetrant carrier for other chemicals are divided in~o two specific schools of thought: those which advocate the use of the pene-trant in concentrations less than 25 percent of the total composition, and those which advocate the concen-tration greater than 50 percent of the total composi-tion. It has been found by this inventor that the optim-al percentage of lower aliphatic sulfoxides to be used as a penetrant and carrier for other active ingredients is between the range of 25 percent and 50 percent of the total composition of the therapeutic compound.
Whenever a concentration greater than 50 percent is employed using a lower aliphatic 6~7~
sulfoxide, and part'icularly DMSO, ~he patien~
experiences a side reaction of a garlic taste in the oral cavi,ty. A test with a percentage of DMSO
greater than 50'percent has indicated that the therapeutic action of the composition is not en-hanced while the'concentration of ~he ~MSO is needlessly high.
Whenever t~e concentration of the lower aliphatic sulfoxide, and particularly DMSO, is less than 25 percent of the total composition, it has been found that the penetrating capabilities of the entire therapeutlc composition is less effective than desired for high-density intra-muscular and intra-articular areas. Consequently, the preferred range has been found ~o be between 25 percent and 50 percent of the total therapeutic composition.
Relief of intra~uscular and intra- ..
articular discomfort must gensrally employ an anti-inflamm~tory agent ~o relieve pain and swel-ling of the discomforted areas. Once again, it has been found that these anti-inflammatory agents are most effective when ~he concentration of the lower aliphatic sulfoxide is between 25 and 50 percent of the total composition~ The therapeutic compositlon may utilize any number of anti-inflamma-tory agents or any combinations of anti-inflammatory agents sufficient to satisfy the particular arti- , cular or muscular treatment desired. '' The use of anti-infla~matory agents through injection into the joint has been found to be detri-mental to the therapy sought. Injections of anti-~ r~, inflammatory agents ~ay, within the Join~, recrysta-lize causing synovitis. Percutaneous penetration does not lead to recrystalization o~ the anti-in1ammatory agen~.
The anti-inflammatory agents of the present invention are classified as physiologically active glucocorticoidal agents, those adrenal cortical steroids which serve to reduce inflam-mation. In the present invention, it has been found that a percentage from about 0.005 to about 0.10 percent o~ the total therapeutic composition should comprise at least one physiologically active glucocorticoidal agent. Preferably, the concen-tra~ion is about 0.025 percent of the total thera-peutic composition.
Physiologically active glucocorticoidal a~en~s include the following natural and synthesized steroids: adrenocorticotropin hormone (ACTH), cortisone, hydrocortisone, prednisone, prednis-2Q olone, triaminolone, methyl prednisolone, mepred-nisone, paramethasone, fluprednisolone, dexametha-sone, and betamethasone. Refinement of the parti-cular glucocorticoidal agent to be used with the treatment of a speciic articular or intra-muscular discomfort depends upon the discomfort involved.
Glucocorticoidal agents are commonly employed for various rheumatic conditions, including, post-traumatic osteoarthritis, synovitis o~ osteoarthri-tis, rheumatoid arthritis, acute and subacute bur-sitis, epicondylitis~ acute nonspécific tenosyno-vitis, acute gouty arthritis, psoriatic arthritis, and ankylosing spondylitis. Typical collagen 7 ~
. ~.
di.seases which glucocorticoidal agents are employed inlude systemic lupus erythemoatosu5, sy8temic dermatomysitis, and acute rheumatic carditis.
These anti-inflammatory agents prevent damage to joint colla~en and bone tissues as caused by abnormal production of collagenase and enzymes in the synovi.al fluid. Synovial cells release la-tent colla~enase which remains latent unless acti-~ated by an actîve enzyme. Rheumato~ cells con-verts inactive plasminogen into active plasminenzyme~ This latter enzyme activates the latent collagenase into active collagenase, which when in th.e synoYial fluid, attacks ~he adjacent col-lagen and bone tissues during joint movement. The anti-inflamma~ory agents, even in a low concentration, inhibit the production of plasminogenand the con-verting substance in the rheumatoid cells, thereby main~aining collagenase in its latent form~ These anti-inflammatory agents also assist in maintain-ing the immune processes within the joints them-selves.
In addition to the lower aliphatic sul-foxide and at least one physiologically active glucocorticoidal agent, the therapeutic composition of the present invention also includes from about 0.25 to about 0.75 percent o$ a topical anesthetic compound. The topical a~esthetic compound may include any compound known to those skilled in the ~.
art to anesthetize the cu~aneous ~urface of the patient. Topical anesthetic compounds include lidocaine, tetracaine, di~ucaine, pramoxire HCl, cyclomethycaine sulfate, di~ethisoquine HCL ethyl 10 .
aminobenzoate (benzocaine), lldocaine HC~, diper-odon, butamben picrate, tetracaine HCl, dyclonine HCl, and hexylcaine HCl. The topical anesthetic compound relieves the cutaneous surface of dis-comfort when the therapeutic composition is applied and the physiologically active glucocorticoidal agent and the percutaneous penetrant are percu-taneously absorbed.
The surface area of the skin over the af-fected joint~ bone, or muscle usually have a number of trigger points associated with myofascial and visceral pains. Brief in~ense stimulation of tri~ger points frequently produces prolonged relief of pain~ It is well known that a short-acting local anesthetic stimulates these trigger points to crea~ a prolonged, perhaps permanent, relief from myo~scial and visceral pain. This in~ense stimulation, called hyperstimulation, is necessary in the therapeutic composition of the present in-vention to relieve pain while the glucocorticoidal agents block acti~ation of collagenase. The syner-gistic combination of analgesia and anti-inflammato-ry medication is only possible with cutaneous applica~ion ha~ing percutaneous penetrants therein.
Because of the continuing controversy surrounding the use of lower aliphatic sulfoxides as claimed active ingredients and as known pene-trants, testing of the therapeutic composition of the present invention was conducted under strict control of availability of material. The lower aliphatic sulfoxides o the present invention ;
have the following formula:
11 .
--'S ~ 1,~, O
- where R and R' are aliphatic hydrocarbon radicals having from l to 5 carbon atoms and may be the same radicals. Prefera~ly, the percutaneous pene-trant of the present invention is dimethyl sul-foxide where R and R' are both methyl groups.
The method o,f treatment ~or the intra-articular and intra-muscular discomfor~ of patients comprises heating the cutaneous surface over the discomforted intra-articular and intra-muscular areas for a few minutes with a warm substance, such as a hot towel or other similar method known to those skilled in the art. If moist heat is used, the cutaneous surface should be dried before applying the topical applica~ion of the therapeutic com-position of the present invention onto the cuta-neous surface. This second step should be enhanced by a gentle rubbing of the surface to enhance the functions of the anesthetic compound and to permit penetration of the percutaneous penetrant and the physiologically active glucocorticoidal agent.
This treatment should be repeated daily or more often until the discomort in the articular and mNscular areas subsides.
The percutaneous penetrant, the topical anesthetic compound and at least one physiologi-cally active glucocorticoidal agent may be mixed with a unibase ointment solvent, commonly known to those skilled in the art. This unibase ointment is water soluble and frequently employed as a - substrate within which the active ingredients 7'7~ ~
12.
of any medication ~ay be used. The unibase ointment comprises glycerine, sodium laurel sulate, sodium citrate, and propyl paraben. The penetrant, anes-thetic compound, and glucocorticoidal agents may be mixed directly into about 100 parts of the unibase ointment solvent, such that the sulfoxide penetrant comprises from about ~5 to about 50 parts, the ~opical anesthetic compound comprises from about 0.25 to about 0.75 parts, and the physiologically active glucocorticoidal agent comprises from about 0~005 to about 0~30 ~arts. Preferably, the pene-trant comprise~s 40 parts, the topical anesthetic compound comprises 0.50 parts, and the glucocorti-coidal agent comprises about 0.025 parts of the therapeutic composition. The relative concentra-tions expressed in parts or percentages of these components of the composition do no~ reflect the solvents or solutions in which they are typically commercially available.
2a INDUSTRIAL APPLICABILITY
The administration of a therapeutic compo-sition of the present invention has achieved sig~
nificant utility by reducing conditions of discom-fort resulting from bursitis, arthritis, and other diseases. The following cases demonstrate the unexpected recovery of patients -following treatment with the therapeutic composition of the present invention.
T~e therapeutic composition was prepared according to the following method. Into about 454 grams of unibase ointment was mixed about ,0 . ....... :
7~
192 milliliters of dimethyl sulfoxide 100 percent solution to create about a 40 percent D~SO pene-tration concentration. Next, approximately 48 milliliters of a 5 percent topical cyclaine 501u-tion was added to the unibase composition to create a 0.5 percent concentration of the topical anes-thetic compound. The 5 percent topical Cyclaine*
solution is commercially available from Merck Sharp Dohme, which serves as a trademark for hexylcaine HCl. To that composition was added two physiologi-cally active glucocortiocoidal agents, the first being approximately 2 l/2 milliliters of ACTH
(40 units / 5 ml) or 100 units of ACTH, a commerci-ally available quantity from Parke-Davis Company.
Finally, approximately 48 milliliters of Decadron*
elixir was added to the therapeutic composition as another glucocorticoidal agent. Decadron* elixir is a commercial quantity available from Merck Sharp Dohme, as a trademark for dexamethasone.
Each milliliter of elixir has 0.1 milligrams of dexamethasone, and the therapeutic composition, therefore, contains 0.000105 percent of the total therapeutic composition.
As an equivalent to lO0 units of ACTH, it has been found that approximately 2 1/2 millili-ters of Depomedrol* (40 mg/ml) may be a physiologi-cally active glucocorticoidal agent. Depomedrol*
(40 mg/ml) is a commercially available quantity available from the UpJohn Company as a trademark for methylprednisolone acetate. This Depomedrol* con-tains 40 milligrams of methylprednisolone acetate per milliliter of solution, which creates a con-centration of glucocorticoidal agent of about .~ *Trademark v;;~ r7 4 4 ~
0~022 pereent of the therapeutic composition~
The following cases ~llustrate ~,he direct, controlled, ~nd immediate therapeutic effect o~
the therapeutic compo3ition for patlents having a Yariety of discomforts~
The patien~ is a m~le, aged 59, who has had therapy for several months on his right shoul-der ~mder the care of several doctors with nosignificant improvement, Upon physical examina-tion, the chief complaints are severe pain in the right shoulder with the inability to raise or ex~end the arm~ The pressure point area of the right shoulder is tender upon pressure, and the orthrodiagram shoulder temperature indicates a chronic pain. Laborato~y tests indicate CBC-normal, WBC-normal~ RA factor-ne~ative, BUN ground range blood sugar-no~mal limi~, The ai~gnosis is acute' and chronic bursitis of the right shoulder.
Therapy was begun with the therapeutic composition, (ACTH formulation), used topically to the shoulder area and muscles, Daily treatment included the application of hot towels for five minutes to ~he area, a drying of the area, and the application of the therapeutic composition with a gentle rubbing of the ointment into the skin, After approximately three weeks of daily treatment J ;', pain has left the right shoulder and complete use 30 of the arm~ including raising and rotating the right arm, was obtained without discomfort.
~ .
~ ~`~
37 ~L
5 ~
CA~2 I'he patient is a male, aged 52 who has been treated by several doctors with intra-articular injections. The physical examination showed chief complaints to be severe pain in right shoulder area and pain radiating down the neck and arm. The arm could not be elevated. Laboratory tests indicated CBC-normal, WBC 8,150, blood sugar-100 milligrams, ~UN-81 milligrams, normal range, cholesterol-284.
The diagnosis is chronic bursitis of the right shoulder~
'rherapy was begun with daily treatments of the therapeutic composition (ACTH formulation) and hot towels as described with Case 1. Daily treatment continues for approximately three weeks.
The present condition finds no pain, a relief of tenderness in the right shoulder~ and the elevation and extension of the right arm, performed without pain. Further, no pressure point pain was found.
The patient is a female~ aged 57 who had visited several doctors with no satisfactory results. Upon physical examination, the chief complaints were the inability to close the fingers to make a fist for both hands. The tenderness in both hands was located in the tendons, which prevented the patient from tying shoelaces or other objects. Laboratory results indicated CBC-adequate, blood sugar-114 milligr~ms, BUN-122 (normal range), cholesterol-224 milligrams, triglycerides-elevated, latex test-negative. The diagnosis was acute tino-ocysnomitis of ligaments of both hands.
.
r ~ 7 ~
Therapy was initiated with daily treatment o~ hot towels applied to thé ingers and wrists on the dorium of the hands for approximately ive minutes, a drying o~ the heated area, and the application and gentle rubbing of the therapeutic composition of the present invention (ACTH ormula-tion). While the treatment continued for several weeks, after one week, the patient was able to tie her shoelaces and make a fist in both hands. Af-ter a few weeks, all pain was relieved and the patient was eventually able to return ~o work and per~orm normal manipuIative duties.
The patient is a female, aged 94. Upon examination, the chief complaints were the inabili-~y by the patient to walk without pain in her hip joints and knee joints. Fhe laboratory results ;
indicate WBC-7800, blood sugar-104, BUN-126 (normal~, cholesterol-225 (elevated), latex-negative, SED.
rate-elevated. The diagnosis is inflammatory arthritis of the knees and hip joints.
Therapy was begun with daily treatment by the application of hot towels to both of the knees and the hip joints for approximately five minutes.
These areas were dried and then the application of the therapeutic composition (ACTH formulation) was gently applied to these areas. Within one and onehalf weeks the patient was ~ree of pain and able ;~
to walk without any discomfor~.
The patient is a male, aged 62. A physical .~.
' , ;
7 7~L
17, examination finds ~he chie~ complaints to ke pain in both knees and hip joints. Laboratory results indicate WBC-660Q~ HB 16-2, SED. rate-26, blood sugar-7~, BUN-9.8, cholesterol-257, trigly-cerides-elevated, antigen check of B13 and B17-presence showing. The diagnosis i5 psoriatic arthritis in both knees and hip joints.
Therapy was initiated with daily treatments to both knees and hip joints, according to the methods described above~ After daily treatment, lasting approximately two weeks, the knees and hip joints were free of pain, and improved motion of the join~s obtained without pain~
The patient is a female, aged 56, who has visited s~veral doc~ors over a period of years for treatment of arthritis. The results have been unsatisfactory. Upon physical examination, the chief complaints are severe pain in the knees, hip joints, and neck areaO Laboratory results indicate WBC-13650, HB-lS.7, blood sugar-89, BUN-8.6, cholesterol-200, triglycerides-125, SED. rate-4 millimeters (9-20 normal), RA latex test-negative.
The diagnosis is infectious arthritis of the knees and hips and neck area.
Therapy was ini~iated wîth the applica-tion of hot towels to the area for approximately 5 ,^, minutes, drying of the area, and a gentle appli 3Q cation of the therapeutic co~position (ACTH formu-lation). This daily treatment continued for sever-al weeks. All symptoms of pain in the affected areas disappeared~ The mov~ment of joints improved ` , , .
18 ~
and ~he WBC count returned to the normal range of 68Q0.
As the case studies indicate, the ther~eutic composition provides a direct~ controlled, and immediate relief to patients who have ~ variety of intra-articular and intra-muscular discomforts.
These representative cases further demonstrate the penetrant capahilities of the ac~ive ingre-dients when the therapeu~ic composi~ion has approxi-mately 40 percent of a lower aliphatic sulfoxide,particularly dimethyl sulfoxide. The action of the anesthetic compound on the trigger points for myo-fascial and visceral pain and the action of the glu-cocorticoidal agents to reduce inflarnmation and inhibit plasminogen production is a synergistic ccmbination in the therapeutic composition ~o satisfy the medicinal needs of those patients.
While in accordance with the patent statutes, a bes~ mode for carrying out the inven-tion has been disclosed, it is to be understoodthat the invention is not limited thereto or there-by. Consequently, for an understanding of the invention, reference is had to the following claims.
CA~2 I'he patient is a male, aged 52 who has been treated by several doctors with intra-articular injections. The physical examination showed chief complaints to be severe pain in right shoulder area and pain radiating down the neck and arm. The arm could not be elevated. Laboratory tests indicated CBC-normal, WBC 8,150, blood sugar-100 milligrams, ~UN-81 milligrams, normal range, cholesterol-284.
The diagnosis is chronic bursitis of the right shoulder~
'rherapy was begun with daily treatments of the therapeutic composition (ACTH formulation) and hot towels as described with Case 1. Daily treatment continues for approximately three weeks.
The present condition finds no pain, a relief of tenderness in the right shoulder~ and the elevation and extension of the right arm, performed without pain. Further, no pressure point pain was found.
The patient is a female~ aged 57 who had visited several doctors with no satisfactory results. Upon physical examination, the chief complaints were the inability to close the fingers to make a fist for both hands. The tenderness in both hands was located in the tendons, which prevented the patient from tying shoelaces or other objects. Laboratory results indicated CBC-adequate, blood sugar-114 milligr~ms, BUN-122 (normal range), cholesterol-224 milligrams, triglycerides-elevated, latex test-negative. The diagnosis was acute tino-ocysnomitis of ligaments of both hands.
.
r ~ 7 ~
Therapy was initiated with daily treatment o~ hot towels applied to thé ingers and wrists on the dorium of the hands for approximately ive minutes, a drying o~ the heated area, and the application and gentle rubbing of the therapeutic composition of the present invention (ACTH ormula-tion). While the treatment continued for several weeks, after one week, the patient was able to tie her shoelaces and make a fist in both hands. Af-ter a few weeks, all pain was relieved and the patient was eventually able to return ~o work and per~orm normal manipuIative duties.
The patient is a female, aged 94. Upon examination, the chief complaints were the inabili-~y by the patient to walk without pain in her hip joints and knee joints. Fhe laboratory results ;
indicate WBC-7800, blood sugar-104, BUN-126 (normal~, cholesterol-225 (elevated), latex-negative, SED.
rate-elevated. The diagnosis is inflammatory arthritis of the knees and hip joints.
Therapy was begun with daily treatment by the application of hot towels to both of the knees and the hip joints for approximately five minutes.
These areas were dried and then the application of the therapeutic composition (ACTH formulation) was gently applied to these areas. Within one and onehalf weeks the patient was ~ree of pain and able ;~
to walk without any discomfor~.
The patient is a male, aged 62. A physical .~.
' , ;
7 7~L
17, examination finds ~he chie~ complaints to ke pain in both knees and hip joints. Laboratory results indicate WBC-660Q~ HB 16-2, SED. rate-26, blood sugar-7~, BUN-9.8, cholesterol-257, trigly-cerides-elevated, antigen check of B13 and B17-presence showing. The diagnosis i5 psoriatic arthritis in both knees and hip joints.
Therapy was initiated with daily treatments to both knees and hip joints, according to the methods described above~ After daily treatment, lasting approximately two weeks, the knees and hip joints were free of pain, and improved motion of the join~s obtained without pain~
The patient is a female, aged 56, who has visited s~veral doc~ors over a period of years for treatment of arthritis. The results have been unsatisfactory. Upon physical examination, the chief complaints are severe pain in the knees, hip joints, and neck areaO Laboratory results indicate WBC-13650, HB-lS.7, blood sugar-89, BUN-8.6, cholesterol-200, triglycerides-125, SED. rate-4 millimeters (9-20 normal), RA latex test-negative.
The diagnosis is infectious arthritis of the knees and hips and neck area.
Therapy was ini~iated wîth the applica-tion of hot towels to the area for approximately 5 ,^, minutes, drying of the area, and a gentle appli 3Q cation of the therapeutic co~position (ACTH formu-lation). This daily treatment continued for sever-al weeks. All symptoms of pain in the affected areas disappeared~ The mov~ment of joints improved ` , , .
18 ~
and ~he WBC count returned to the normal range of 68Q0.
As the case studies indicate, the ther~eutic composition provides a direct~ controlled, and immediate relief to patients who have ~ variety of intra-articular and intra-muscular discomforts.
These representative cases further demonstrate the penetrant capahilities of the ac~ive ingre-dients when the therapeu~ic composi~ion has approxi-mately 40 percent of a lower aliphatic sulfoxide,particularly dimethyl sulfoxide. The action of the anesthetic compound on the trigger points for myo-fascial and visceral pain and the action of the glu-cocorticoidal agents to reduce inflarnmation and inhibit plasminogen production is a synergistic ccmbination in the therapeutic composition ~o satisfy the medicinal needs of those patients.
While in accordance with the patent statutes, a bes~ mode for carrying out the inven-tion has been disclosed, it is to be understoodthat the invention is not limited thereto or there-by. Consequently, for an understanding of the invention, reference is had to the following claims.
Claims (9)
1. A therapeutic composition for the relief of intra-articular and intra-muscular discomfort be-neath cutaneous surfaces, characterized by:
(a) from about 25 to less than 50 parts by weight of a percutaneous penetrant selected from sulfoxides having the following formula:
R-?-R' where R and R' are aliphatic hydrocarbon radicals hav-ing from 1 to 5 carbon atoms and may be the same group;
(b) from about 0.25 to about 0.75 parts by weight of a topical anesthetic compound; and (c) from about 0.005 to about 0.10 parts by weight of at least one physiologically active gluco-corticoidal agent selected from the group consisting of: adrenocoricotropin hormone (ACTH), cortisone, hydro-cortisone, prednisone, prednisolone, triaminolone, methyl prednisolone, meprednisone, paramethasone, flu-prednisolone, dexamethasone, and betamethasone.
(a) from about 25 to less than 50 parts by weight of a percutaneous penetrant selected from sulfoxides having the following formula:
R-?-R' where R and R' are aliphatic hydrocarbon radicals hav-ing from 1 to 5 carbon atoms and may be the same group;
(b) from about 0.25 to about 0.75 parts by weight of a topical anesthetic compound; and (c) from about 0.005 to about 0.10 parts by weight of at least one physiologically active gluco-corticoidal agent selected from the group consisting of: adrenocoricotropin hormone (ACTH), cortisone, hydro-cortisone, prednisone, prednisolone, triaminolone, methyl prednisolone, meprednisone, paramethasone, flu-prednisolone, dexamethasone, and betamethasone.
2. A therapeutic composition according to claim 1, further characterized in that the composition fur-ther comprises about 100 parts of a unibase ointment solvent, said solvent comprising glycerine, sodium laurel sulfate, sodium citrate, and propyl paraben.
3. A therapeutic composition according to claim 1, further characterized in that there are two physi-ologically active glucocorticoidal agents in the thera-peutic composition, and wherein the amount of said penetrant is about 40 parts by weight.
4. A therapeutic composition according to claim 3 further characterized in that said physiolog-ically active glucocorticoidal agents comprise from about 0.00005 parts to about 0.099 parts of dexametha-sone, and from about 0.001 parts to about 0.009 parts of methyl prednisolone.
5. A therapeutic composition according to claim 4 further characterized in that said physiologically active glucocorticoidal agent comprises about 0.00011 parts of dexamethasone and about 0.022 parts of methyl prednisolone.
6. A therapeutic composition according to claim 3 further characterized in that said physiologically active glucocorticoidal agent comprises from about 0.00005 parts to about 0.099 parts of dexamethasone and from about 0.001 parts to about 0.099 parts of adreno corticotropin hormone.
7. A therapeutic composition according to claim 6 further characterized in that said physiologically active glucocorticoidal agent comprises about 0.00011 parts of dexamethasone and about 0.022 parts of methyl prednisolone.
8. A therapeutic composition according to claim 1 further characterized in that said percutaneous penetrant comprises dimethyl sulfoxide.
9. A therapeutic composition according to claim 3 further characterized in that said topical anesthetic compound is selected from the group con-sisting of lidocaine, tetracaine, dibucaine, pramox-ire HC1, cyclomethycaine sulfate, dimethisoquine HC1, ethyl aminobenzoate (benzocaine), lidocaine HC1, diperodon, butamben picrate, tetracaine HCl, dyclo-nine HC1, hexylcaine, HC1, and combinations thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/166,307 US4312865A (en) | 1980-07-07 | 1980-07-07 | Medication having penetration through cutaneous surfaces into articular and muscular areas |
| US166,307 | 1980-07-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1169774A true CA1169774A (en) | 1984-06-26 |
Family
ID=22602702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000375605A Expired CA1169774A (en) | 1980-07-07 | 1981-04-15 | Medication having penetration through cutaneous surfaces into articular and muscular areas |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US4312865A (en) |
| CA (1) | CA1169774A (en) |
| GB (1) | GB2079151B (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4818707A (en) * | 1983-04-21 | 1989-04-04 | Breneman James C | Device and mixture for testing for immune responses to food |
| US4917894A (en) * | 1988-06-29 | 1990-04-17 | Beecham Inc. | Rapid-onset long-duration oral anesthetic composition |
| US5478565A (en) * | 1990-03-27 | 1995-12-26 | Warner-Lambert Company | Treatment of sinus headache |
| FR2704147B1 (en) * | 1993-04-22 | 1995-07-21 | Leguern Jacques | Cell regenerating composition and its application in medical, veterinary and agricultural environments. |
| US7601707B1 (en) * | 2003-03-05 | 2009-10-13 | Minks William J | Method for instantly relieving tissue inflammation |
| WO2005032521A2 (en) * | 2003-10-02 | 2005-04-14 | Collegium Pharmaceutical, Inc. | Non-flammable topical anesthetic liquid aerosols |
| US20060188449A1 (en) * | 2003-10-03 | 2006-08-24 | Jane Hirsh | Topical aerosol foams |
| US20070134232A1 (en) * | 2005-12-14 | 2007-06-14 | Joel Studin | Topical bite care composition |
| US8652443B2 (en) * | 2008-02-14 | 2014-02-18 | Precision Dermatology, Inc. | Foamable microemulsion compositions for topical administration |
| WO2018160212A1 (en) * | 2017-02-28 | 2018-09-07 | Backer John W | Dimethyl sulfoxide (dmso) and hydrocortisone compositions and methods of use |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4177267A (en) * | 1963-12-09 | 1979-12-04 | Crown Zellerbach | Enhancing tissue penetration of physiologically active steroidal agents with DMSC |
| US4130667A (en) * | 1976-01-12 | 1978-12-19 | The Procter & Gamble Company | Dermatological compositions |
-
1980
- 1980-07-07 US US06/166,307 patent/US4312865A/en not_active Expired - Lifetime
-
1981
- 1981-04-15 CA CA000375605A patent/CA1169774A/en not_active Expired
- 1981-05-06 GB GB8113861A patent/GB2079151B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2079151A (en) | 1982-01-20 |
| US4312865A (en) | 1982-01-26 |
| GB2079151B (en) | 1984-05-31 |
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