CA2003177A1 - Treatment of skin diseases with artemisinin and derivatives - Google Patents
Treatment of skin diseases with artemisinin and derivativesInfo
- Publication number
- CA2003177A1 CA2003177A1 CA 2003177 CA2003177A CA2003177A1 CA 2003177 A1 CA2003177 A1 CA 2003177A1 CA 2003177 CA2003177 CA 2003177 CA 2003177 A CA2003177 A CA 2003177A CA 2003177 A1 CA2003177 A1 CA 2003177A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- artemisinin
- treatment
- accordance
- subject
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Abstract
TREATMENT OF SKIN DISEASES
WITH ARTEMISININ AND DERIVATIVES
ABSTRACT OF THE DISCLOSURE
Psoriasis, ultraviolet light induced skin conditions and tumors are successfully treated with topical or oral administration of artemisinin, dihydroartemisinin, its semisynthetic derivatives and its synthetic analogs.
Viral tumors/diseases, hemorrhoids, and bullous skin diseases are also successfully treated with these topical compositions.
WITH ARTEMISININ AND DERIVATIVES
ABSTRACT OF THE DISCLOSURE
Psoriasis, ultraviolet light induced skin conditions and tumors are successfully treated with topical or oral administration of artemisinin, dihydroartemisinin, its semisynthetic derivatives and its synthetic analogs.
Viral tumors/diseases, hemorrhoids, and bullous skin diseases are also successfully treated with these topical compositions.
Description
3~77 TREATMENT OF SKIN DISEASES
WITH ARTEMISININ AND DERIVATIVES
This invention relates to the topical and/or systemic treatment of psoriasis, viral- or ultraviolet radiation-induced skin diseases and skin tumors, and other related conditions with a class of compounds having sesquiterpene structures, including artemisinin, dihydroartemislnin, and derivatives and analogs of these compounds.
Psoriasis is a common skin disease characterized by hyperactive keratinocytes whose metabolism is increased nine-fold. The skin lesions generally are thick scales on sharply demarcated red plaques. The involved and uninvolved skin lesions have markedly elevated levels of the regulatory 25 ~ proteins putrescine and spermidine and suppressed local cell mediated immunity. No current therapies, includin~
corticosteroids, retinoids, and immunosuppressive~agents are effective in curing this disease, significantly decre~asing the levels of these two polyamines, or~stimulating lesional~
cell mediated immunity. ~ ~ ~
The polyamines of concern in this invention are generally low molecular weight, long chain, cationic aliphatic compounds with multiple amine and/or imino groups.
These compounds are~widely distributed in nature.
Putrescine, spermidines and spermine are the major poly~mlnes found in m .
; ' ' 2~03~L77 Ultraviolet radiation is invisible light that induces a number of diseases, including polymorphous light eruption, collagen vascular diseases, premalignant keratoses, and primary skin cancer. Current therapies include topical sunscreens~ immunosuppressive agents, corticosteroids, and sur~ery or destruction of the premalignant and malignant lesions.
Treatment of viral tumors/diseases (warts, molluscum contagiosum) and hemorrhoids suffer from being usually inefective but painful. Unlike most viral infec-tionsl the wart virus produces hypertrophic viable cells and suppresses skin cellular immunity against the virus.
Pemphigoid and pemphigus are autoimmune blistering diseases whose incidence increases with age and are life threatening. Unfortunately, a significant percentage of deaths are due to massive doses of the therapeutic agents, corticosteroids and immunosuppressives.
Artemisinin or Qinghaosu is a proven systemic antimalarial agent purified from the herb Artemisia Annua.
Artemisinin is a sesquiterpene lactone with a peroxide grouping that is water insoluble but is extremely safe.
There are single reports from China that artemisinin was 1) virustatic against influenza virus in chick embryo, 2) beneficial in a case of systemic lupus erythematosus, 3) suppresses humoral immunity, 4) stimulates cell mediated immunity, and 5) significantly decreases levels of all three human polyamines, especialy putrescine and spermidine.
In an effort to improve water solubility and decrease recurrences, scientists have developed semisynthetic derivatives and synthetic analogs of artemisinin. These compounds display the aforementioned sought after characteristics with -the added benefit of increased antimalarial activity. These compounds have never been studied for therapeutic activlty in any primary skin diseases or tumors and along with artemisinin have never been used as a topical treatment for any disease.
~ .:
WITH ARTEMISININ AND DERIVATIVES
This invention relates to the topical and/or systemic treatment of psoriasis, viral- or ultraviolet radiation-induced skin diseases and skin tumors, and other related conditions with a class of compounds having sesquiterpene structures, including artemisinin, dihydroartemislnin, and derivatives and analogs of these compounds.
Psoriasis is a common skin disease characterized by hyperactive keratinocytes whose metabolism is increased nine-fold. The skin lesions generally are thick scales on sharply demarcated red plaques. The involved and uninvolved skin lesions have markedly elevated levels of the regulatory 25 ~ proteins putrescine and spermidine and suppressed local cell mediated immunity. No current therapies, includin~
corticosteroids, retinoids, and immunosuppressive~agents are effective in curing this disease, significantly decre~asing the levels of these two polyamines, or~stimulating lesional~
cell mediated immunity. ~ ~ ~
The polyamines of concern in this invention are generally low molecular weight, long chain, cationic aliphatic compounds with multiple amine and/or imino groups.
These compounds are~widely distributed in nature.
Putrescine, spermidines and spermine are the major poly~mlnes found in m .
; ' ' 2~03~L77 Ultraviolet radiation is invisible light that induces a number of diseases, including polymorphous light eruption, collagen vascular diseases, premalignant keratoses, and primary skin cancer. Current therapies include topical sunscreens~ immunosuppressive agents, corticosteroids, and sur~ery or destruction of the premalignant and malignant lesions.
Treatment of viral tumors/diseases (warts, molluscum contagiosum) and hemorrhoids suffer from being usually inefective but painful. Unlike most viral infec-tionsl the wart virus produces hypertrophic viable cells and suppresses skin cellular immunity against the virus.
Pemphigoid and pemphigus are autoimmune blistering diseases whose incidence increases with age and are life threatening. Unfortunately, a significant percentage of deaths are due to massive doses of the therapeutic agents, corticosteroids and immunosuppressives.
Artemisinin or Qinghaosu is a proven systemic antimalarial agent purified from the herb Artemisia Annua.
Artemisinin is a sesquiterpene lactone with a peroxide grouping that is water insoluble but is extremely safe.
There are single reports from China that artemisinin was 1) virustatic against influenza virus in chick embryo, 2) beneficial in a case of systemic lupus erythematosus, 3) suppresses humoral immunity, 4) stimulates cell mediated immunity, and 5) significantly decreases levels of all three human polyamines, especialy putrescine and spermidine.
In an effort to improve water solubility and decrease recurrences, scientists have developed semisynthetic derivatives and synthetic analogs of artemisinin. These compounds display the aforementioned sought after characteristics with -the added benefit of increased antimalarial activity. These compounds have never been studied for therapeutic activlty in any primary skin diseases or tumors and along with artemisinin have never been used as a topical treatment for any disease.
~ .:
3~77 Treating primary skin disease and tumors with topically applied dru~s improves safety, therapeutic success, and is much more cost effective. All topical drugs must penetrate the stratum corneum "barrier" to be effective. Nearly all drugs do not penetrate so penetration enhancers or vehicles have been developed to cross this barrier. When combined with the active drug, a dramatic improvement in therapeutic effectiveness occurs.
It has been discovered that compounds having structures which contain sesquiterpene groups are effective therapeutic agents useful in the treatment of a group of skin conditions. Included among these skin conditions are psoriasis; diseases and tumors induced by ultraviolet radiation or of viral origin, including primary plemalignant and malignant skin tumors; blisteriny skin diseases; and hemorrhoids. Skin conditions induced by utraviolet radiation include polymorphous light eruption, collagen vascular disease, premalignant keratoses, Bowen's disease, lentigo maligna, basal cell cancer, squamous cell cancer, and malignant melanomas. Tumors and diseases of viral origin include warts, molluscum contagiosum, orf and ecthyma contagiosum.
The compounds which are discovered to have these properties, in accordance with t.his invention, include artemisinin; dihydroartemisinin; carbonate, sulfonate, ester, and ether derivatives of dihydroartemisinin, notably artemether, artesunate and artesunate salts, and dihydroartemisinin propyl carbonate~ as well as the bis-ether artelinic acid. In the practice of the invention, formulations of these compoun~s are administered 0ither parenterally, orally, or topically. For topical administration, the compounds are preferably formulated with vehicles ~hich enhance the penetration of the formulAtions through the stratum corneum. These toplcal formulations are .
2~03~
particularly effective in the treatment of viral tumors and diseases, blistering diseases and hemorrhoids.
In accordance with the invention, it has been discovered that compounds within this class significantly suppress all three major polyamines found in man, especially putrescine and spermine.
The compounds applied in accordance with the present invention are generally those whose molecular formulas include a sesquiterpene structure, preferably a sesquiterpene lactone with an attached peroxide. Within this group, those which are particularly preferred are artemisinin, dihydroartemisinin, semisynthetic derivatives of dihydroartemisinin including propyl carbonate dihydroartemisinin, artemether, artesunate, and other ethers, esters, carbonates and sulfonates, and the synthetic analog, artelinic acid. These compounds, when formulated for systemic administration or formulatéd with vehicles for topical application effectively treat psoriasis, collagen vascular diseases, polymorphous light eruption, xeroderma pigmentosa, premalignant actinic keratoses and Bowen s diseases, and basal cell, squamous cell, and melanoma skin cancers. These topical formulations also effectively treat hemorrhoids, viral induced tumors lwarts) and diseases, pemphigoid and pemphigus. The collagen vascular diseases include lupus er~thematosus, mixed~connective tissue diseases, and dermatomyositis.
The compounds used in the present invention include those falllng withln the following generic formula: -:
' ' ,~' ,' 2~)~3~
5~ ` ~
H3C ~ "`o~ " ~ J (I) 0 / \~
1 ¦ H
O ~H
where R is either --C-- --CH--(artemisinin) (dihydroartemisinin) -CH-or ll O~R' in which R' is as follows:
-C-O-alkyl, -C-O-aryl, (carbonates~
o O , o o O O
. -C-alkyl, -C-aryl, -C-alkylene-C-OH, -C-alkylene-C-O M~, (esters) alkyl, (ethers~
O O
-S-O-alkyl or -S-O-aryl . ~ (~sulfonates) ~
In the R' definition, the terms "alkyl" and "alkylene~"
preferably refer to lower alkyl or alkylene groups, notably Cl-C6, with Cl-C4 most preferred. Straight-chain and branched-chain groups are included, with straight-chain groups preferred. The term "aryl" preferably re~ers to phenyl and naphthyl, with phenyl the~most preferred. The symbol M in Formula I is an alkali or alkaline earth ~etal, preferably sodium or potassium, wlth sodium the most 2003~
preferred. The ester in which R is -C(0)-(CH2~2-CO2H is known by the common names artesunic acid and artesunate, and the ester in which R is -C(0)-~CH2)2-C02 Na~ is known as sodium artesunate.
Also included is the bis-ether, artelinic acid, having the formula:
15H3C ~ ~ ~0 ~: O ~
I I ~H
0 ~ ~ H
~CH3 o (II) ~ ~ H3 I"H
~
CH3 ~ -. .
The concentrations of the sesquiterpene structure compounds~1n the formulations to be~applied in~the practice of the present invention are not critical and may vary widely. In most appllcations, however,;~best r~esults will be obtained using formulations containing the compounds at levels of from about 0.01% to about 35% by weight, preferably from about 0.5% to about 15%. The amount of the compound actually administered ~or treatment will be a therapeutically effective amountj which term is used herein to denote the amount needed to produce a substantial , clinical improvement. ~ptimal amounts will vary with the method of administration, and will generally be in accordance with the amounts of conventional medicaments administered in the same or a similar ~orm. Topical application, for instance, is typically done from once to three time~ a day.
The topical formulations may further include one or more of the wide variety of agents known to be e~fective as skin penetration enhancers. Examples of these are 2-pyrrolidone, N-methyl-2-pyrrolidone, dimethylacetamide, dimethylformamide, propylene glycol, alcohol, dimethyl sulfoxide~ and ~æone. Additional agents may further be included to make the formulation cosmetically acceptable.
Examples of these are ~ats, waxes, oils, dyes, fragrance, preservatives, stabilizers, and surface active agents.
Keratolytic agents such as those known in the art may also be included. Examples are salicylic acid, sulfur, transretinoic acid and later generations of retinoids.
The amounts of each of these various types of additive will be readily apparent to those skilled in the art optimal amounts being the same as in other, known formulations designed for the same type of administration. Stratum corneum penetration enhancers.
for example, will typically be included at levels within the range of about 0.1% to ahout 30% by weight, preferably from about 1% to about 15%.
The following examples are offered for purposes of illustration, and are intended neither to define nor limit the invention in any manner.
Three patients with plaque psoriasis were treated with an ointment containing artemisinin at 1% by weight in a four-week, three-leg, open-paired comparison patch study~ Trunkal or proximal extremity p oriatic plaques 1.5 to 3 centimeters in diameter that had been stable for at least four weeks were treated.
The test consisted of applyin~ three different formulations to separate test areas on each of three patients. The formulations were a~ follows:
(a) 1% artemisinin ointment without added penetration enhancers;
(b) Aristocort A 0.1% cream, a Class IV
corticosteroid; and (c) Diprolene ointment, a Clas~ I corticosteroid.
Formulations (a) and (b) were applied twice daily and occluded with an elastic cloth bandage. The third was applied twice daily without occlusion. The lesions were examined weekly.
One patient experienced 100% clearing of all three test areas, while his untreated plaque~ improved by 50%, probably indicating some spontaneous remission. ~he three treated areas~ however, cleared faster and more completely than the untreated areas, indioating that the formulations did have a therapeutic effect.
On the second patient, the plaque treated with ;
formulation (a) improved by 75%. This plaque displayed 2+
erythema, but had no scale and was ~lat. By contrast, the plaque treated with formulation (b) improved by only 25%, while the plaque treated with formulation (c) remained unchanged.
::
On the third patient, the plaque treated with formulation (a~ improved by 50% with 1~ violaceous erythema, but with à 1+ elevated and 1~ scaley peripheral rim. The plaque treated with formulation ~b) improved by only 25%, while the plaque treated with formulation (c) was 100% clear except for 1+ post inflammatory hyperpigmentation.
,.~.~`
The conclusion from these tests is that occluded artemisinin is superior to an occluded mid-potency topical corticosteroid, and comparable to a megapotent topical corticosteroid.
~XAMPLE 2 Three patents, each with one to three external haemorrhoids that did not improve upon treatment with either Anusol H~ or Preparation H~, two commercially available haemorrhoids treatment products, were treated with an ointment containing 1% artemisinin by weight (without the inclusion of penetration-enhancing additives), by topical administration applied four times daily. All patients experienced relief of the itching, tenderness and swelling symptoms after four to six days of the treatment.
The foregoing is offered primarily for purposes of illustration. It will be readily apparent to those skilled in the art that further variations in the formulations and uses of the compounds beyond those described herein may be made without departing;from the spirit or scope of the invention.
, I
~'
It has been discovered that compounds having structures which contain sesquiterpene groups are effective therapeutic agents useful in the treatment of a group of skin conditions. Included among these skin conditions are psoriasis; diseases and tumors induced by ultraviolet radiation or of viral origin, including primary plemalignant and malignant skin tumors; blisteriny skin diseases; and hemorrhoids. Skin conditions induced by utraviolet radiation include polymorphous light eruption, collagen vascular disease, premalignant keratoses, Bowen's disease, lentigo maligna, basal cell cancer, squamous cell cancer, and malignant melanomas. Tumors and diseases of viral origin include warts, molluscum contagiosum, orf and ecthyma contagiosum.
The compounds which are discovered to have these properties, in accordance with t.his invention, include artemisinin; dihydroartemisinin; carbonate, sulfonate, ester, and ether derivatives of dihydroartemisinin, notably artemether, artesunate and artesunate salts, and dihydroartemisinin propyl carbonate~ as well as the bis-ether artelinic acid. In the practice of the invention, formulations of these compoun~s are administered 0ither parenterally, orally, or topically. For topical administration, the compounds are preferably formulated with vehicles ~hich enhance the penetration of the formulAtions through the stratum corneum. These toplcal formulations are .
2~03~
particularly effective in the treatment of viral tumors and diseases, blistering diseases and hemorrhoids.
In accordance with the invention, it has been discovered that compounds within this class significantly suppress all three major polyamines found in man, especially putrescine and spermine.
The compounds applied in accordance with the present invention are generally those whose molecular formulas include a sesquiterpene structure, preferably a sesquiterpene lactone with an attached peroxide. Within this group, those which are particularly preferred are artemisinin, dihydroartemisinin, semisynthetic derivatives of dihydroartemisinin including propyl carbonate dihydroartemisinin, artemether, artesunate, and other ethers, esters, carbonates and sulfonates, and the synthetic analog, artelinic acid. These compounds, when formulated for systemic administration or formulatéd with vehicles for topical application effectively treat psoriasis, collagen vascular diseases, polymorphous light eruption, xeroderma pigmentosa, premalignant actinic keratoses and Bowen s diseases, and basal cell, squamous cell, and melanoma skin cancers. These topical formulations also effectively treat hemorrhoids, viral induced tumors lwarts) and diseases, pemphigoid and pemphigus. The collagen vascular diseases include lupus er~thematosus, mixed~connective tissue diseases, and dermatomyositis.
The compounds used in the present invention include those falllng withln the following generic formula: -:
' ' ,~' ,' 2~)~3~
5~ ` ~
H3C ~ "`o~ " ~ J (I) 0 / \~
1 ¦ H
O ~H
where R is either --C-- --CH--(artemisinin) (dihydroartemisinin) -CH-or ll O~R' in which R' is as follows:
-C-O-alkyl, -C-O-aryl, (carbonates~
o O , o o O O
. -C-alkyl, -C-aryl, -C-alkylene-C-OH, -C-alkylene-C-O M~, (esters) alkyl, (ethers~
O O
-S-O-alkyl or -S-O-aryl . ~ (~sulfonates) ~
In the R' definition, the terms "alkyl" and "alkylene~"
preferably refer to lower alkyl or alkylene groups, notably Cl-C6, with Cl-C4 most preferred. Straight-chain and branched-chain groups are included, with straight-chain groups preferred. The term "aryl" preferably re~ers to phenyl and naphthyl, with phenyl the~most preferred. The symbol M in Formula I is an alkali or alkaline earth ~etal, preferably sodium or potassium, wlth sodium the most 2003~
preferred. The ester in which R is -C(0)-(CH2~2-CO2H is known by the common names artesunic acid and artesunate, and the ester in which R is -C(0)-~CH2)2-C02 Na~ is known as sodium artesunate.
Also included is the bis-ether, artelinic acid, having the formula:
15H3C ~ ~ ~0 ~: O ~
I I ~H
0 ~ ~ H
~CH3 o (II) ~ ~ H3 I"H
~
CH3 ~ -. .
The concentrations of the sesquiterpene structure compounds~1n the formulations to be~applied in~the practice of the present invention are not critical and may vary widely. In most appllcations, however,;~best r~esults will be obtained using formulations containing the compounds at levels of from about 0.01% to about 35% by weight, preferably from about 0.5% to about 15%. The amount of the compound actually administered ~or treatment will be a therapeutically effective amountj which term is used herein to denote the amount needed to produce a substantial , clinical improvement. ~ptimal amounts will vary with the method of administration, and will generally be in accordance with the amounts of conventional medicaments administered in the same or a similar ~orm. Topical application, for instance, is typically done from once to three time~ a day.
The topical formulations may further include one or more of the wide variety of agents known to be e~fective as skin penetration enhancers. Examples of these are 2-pyrrolidone, N-methyl-2-pyrrolidone, dimethylacetamide, dimethylformamide, propylene glycol, alcohol, dimethyl sulfoxide~ and ~æone. Additional agents may further be included to make the formulation cosmetically acceptable.
Examples of these are ~ats, waxes, oils, dyes, fragrance, preservatives, stabilizers, and surface active agents.
Keratolytic agents such as those known in the art may also be included. Examples are salicylic acid, sulfur, transretinoic acid and later generations of retinoids.
The amounts of each of these various types of additive will be readily apparent to those skilled in the art optimal amounts being the same as in other, known formulations designed for the same type of administration. Stratum corneum penetration enhancers.
for example, will typically be included at levels within the range of about 0.1% to ahout 30% by weight, preferably from about 1% to about 15%.
The following examples are offered for purposes of illustration, and are intended neither to define nor limit the invention in any manner.
Three patients with plaque psoriasis were treated with an ointment containing artemisinin at 1% by weight in a four-week, three-leg, open-paired comparison patch study~ Trunkal or proximal extremity p oriatic plaques 1.5 to 3 centimeters in diameter that had been stable for at least four weeks were treated.
The test consisted of applyin~ three different formulations to separate test areas on each of three patients. The formulations were a~ follows:
(a) 1% artemisinin ointment without added penetration enhancers;
(b) Aristocort A 0.1% cream, a Class IV
corticosteroid; and (c) Diprolene ointment, a Clas~ I corticosteroid.
Formulations (a) and (b) were applied twice daily and occluded with an elastic cloth bandage. The third was applied twice daily without occlusion. The lesions were examined weekly.
One patient experienced 100% clearing of all three test areas, while his untreated plaque~ improved by 50%, probably indicating some spontaneous remission. ~he three treated areas~ however, cleared faster and more completely than the untreated areas, indioating that the formulations did have a therapeutic effect.
On the second patient, the plaque treated with ;
formulation (a) improved by 75%. This plaque displayed 2+
erythema, but had no scale and was ~lat. By contrast, the plaque treated with formulation (b) improved by only 25%, while the plaque treated with formulation (c) remained unchanged.
::
On the third patient, the plaque treated with formulation (a~ improved by 50% with 1~ violaceous erythema, but with à 1+ elevated and 1~ scaley peripheral rim. The plaque treated with formulation ~b) improved by only 25%, while the plaque treated with formulation (c) was 100% clear except for 1+ post inflammatory hyperpigmentation.
,.~.~`
The conclusion from these tests is that occluded artemisinin is superior to an occluded mid-potency topical corticosteroid, and comparable to a megapotent topical corticosteroid.
~XAMPLE 2 Three patents, each with one to three external haemorrhoids that did not improve upon treatment with either Anusol H~ or Preparation H~, two commercially available haemorrhoids treatment products, were treated with an ointment containing 1% artemisinin by weight (without the inclusion of penetration-enhancing additives), by topical administration applied four times daily. All patients experienced relief of the itching, tenderness and swelling symptoms after four to six days of the treatment.
The foregoing is offered primarily for purposes of illustration. It will be readily apparent to those skilled in the art that further variations in the formulations and uses of the compounds beyond those described herein may be made without departing;from the spirit or scope of the invention.
, I
~'
Claims (12)
1. A method for the treatment of a subject suffering from psoriasis, said method comprising administering to said subject a therapeutically effective amount of a compound containing a sesquiterpene structure.
2. A method for the treatment of a subject suffering from an ultraviolet radiation induced disease or tumor, including polymorphous light eruption, collagen vascular disease, premalignant keratoses, Bowen's disease, lentigo maligna, basal cell cancer, squamous cell cancer, and malignant melanoma, said method comprising administering to said subject a therapeutically effective amount of a compound containing a sesquiterpene structure.
3. A method for the treatment of a subject suffering from viral tumors or diseases, including warts, molluscum contagiosum, orf, and ecthyma contagiosum, said method comprising administering to said subject a therapeutically effective amount of a compound containing a sesquiterpene structure.
4. A method for the treatment of a subject suffering from a blistering skin disease, said method comprising administering to said subject a composition containing a therapeutically effective amount of a compound containing a sesquiterpene structure.
5. A method for the treatment of a subject suffering from hemorrhoids, said method comprising applying to said subject a composition containing a therapeutically effective amount of a compound containing a sesquiterpene structure.
6. A method in accordance with any of claims 1, 2, 3, 4 or 5 in which said compound is a sesquiterpene lactone with an attached peroxide.
7. A method in accordance with any of claims 1, 2, 3, 4 or 5 in which said compound is one having the formula where R is a member selected from the group consisting of -?- , and in which R' is a member selected from the group consisting of ?-O-alkyl, ?-O-aryl, -?-alkyl, -?-aryl, -?-alkylene-?-OH, -?-alkylene-?-O M?, alkyl, ?-O-alkyl and ?-O-aryl, in which M is sodium or potassium.
8. A method in accordance with any of claims 1, 2, 3, 4 or 5 in which said compound is a synthetic analog of dihydroartemisinin.
9. A method in accordance with any of claims 1, 2, 3, 4 or 5 in which said compound is artelinic acid.
10. A method in accordance with any of claims 1, 2, 3, 4 or 5 in which said compound is a semisynthetic derivative of dihydroartemisinin selected from the group consisting of esters, ethers, carbonates and sulfonates.
11. A method in accordance with any of claims 1, 2, 3, 4 or 5 in which said compound is a member selected from the group consisting of artemisinin, dihydro-artemisinin, artemether, artesunate, and dihydroartemisinin propyl carbonate.
12. A method in accordance with any of claims 1, 2, 3, 4 or 5 in which said compound is a member selected from the group consisting of artemisinin, dihydro-artemisinin, artemether, artesunate, and dihydroartemisinin propyl carbonate; and said composition further contains a member selected from the group consisting of N-methyl-2-pyrrolidone and dimethylacetamide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2003177 CA2003177A1 (en) | 1989-11-16 | 1989-11-16 | Treatment of skin diseases with artemisinin and derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2003177 CA2003177A1 (en) | 1989-11-16 | 1989-11-16 | Treatment of skin diseases with artemisinin and derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2003177A1 true CA2003177A1 (en) | 1991-05-16 |
Family
ID=4143578
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2003177 Abandoned CA2003177A1 (en) | 1989-11-16 | 1989-11-16 | Treatment of skin diseases with artemisinin and derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2003177A1 (en) |
-
1989
- 1989-11-16 CA CA 2003177 patent/CA2003177A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4978676A (en) | Treatment of skin diseases with artemisinin and derivatives | |
| US5219880A (en) | Treatment of viral tumors and hemorrhoids with artemisinin and derivatives | |
| Premalatha | Semecarpus anacardium Linn. nuts—a boon in alternative medicine | |
| US20080119542A1 (en) | Methods of using artemisinin-like compounds to prevent or delay the appearance of cancer | |
| US8557829B2 (en) | Use of allopurinol for the treatment of palmar plantar erythrodysesthesia | |
| HU203201B (en) | Process for producing antitumoural pharmaceutical composition having synergetic effect | |
| US6465512B2 (en) | Leukemic cell growth inhibiting method | |
| US6197808B1 (en) | Methods for treating hyperplasia | |
| KR20010031407A (en) | Use of coumarin derivatives for the treatment of digestive tract disorders | |
| AU2003204391B2 (en) | Composition and its therapeutic use | |
| CA2145229A1 (en) | Suppressory compositions against hepatic metastases of tumors | |
| EP0535719A2 (en) | Treatment of hemorrhoids with artemisinin and derivates | |
| Bullen et al. | Skin reactions caused by vitamin K in patients with liver disease | |
| US8263567B2 (en) | Treatment of hyperproliferative conditions of body surfaces | |
| CA1172168A (en) | Deazapurine nucleoside, formulations thereof, and use thereof in therapy | |
| JPH03170422A (en) | Treatment of skin disease | |
| CA2003177A1 (en) | Treatment of skin diseases with artemisinin and derivatives | |
| US5552436A (en) | Process for treating hemangioma | |
| JPH05501542A (en) | Use of C-20 to C-26 fatty alcohols in the treatment of viral infections | |
| Basak et al. | Should pentoxifylline be regarded as an effective treatment for Schamberg's disease? | |
| EP0247900B1 (en) | Topical methotrexate preparation for the treatment of hyperproliferative epithelial disease | |
| NZ205587A (en) | Composition comprising undecylenic acid for treating herpes simplex i | |
| AU2002320964A1 (en) | Treatment of hyperproliferative conditions of body surfaces | |
| BRPI0711847A2 (en) | uses of allopurinol for the treatment or prevention of plantar palm erythrodysesthesia, pharmaceutical composition for topical administration to the skin and method for the treatment or prevention of plantar palm erythrodysesthesia | |
| EP2456423A2 (en) | Treatment of hyperproliferative conditions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |