NZ702424B2 - Composition for treatment of warts - Google Patents
Composition for treatment of warts Download PDFInfo
- Publication number
- NZ702424B2 NZ702424B2 NZ702424A NZ70242412A NZ702424B2 NZ 702424 B2 NZ702424 B2 NZ 702424B2 NZ 702424 A NZ702424 A NZ 702424A NZ 70242412 A NZ70242412 A NZ 70242412A NZ 702424 B2 NZ702424 B2 NZ 702424B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- composition
- warts
- formic acid
- acid
- ethyl lactate
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 186
- 201000010153 skin papilloma Diseases 0.000 title claims abstract description 144
- 208000000260 Warts Diseases 0.000 title claims abstract description 132
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 210
- 235000019253 formic acid Nutrition 0.000 claims abstract description 70
- LZCLXQDLBQLTDK-UHFFFAOYSA-N Ethyl lactate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 claims abstract description 51
- 229940116333 ethyl lactate Drugs 0.000 claims abstract description 48
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims abstract description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 24
- 239000004310 lactic acid Substances 0.000 claims abstract description 24
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 24
- 230000000699 topical Effects 0.000 claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- 210000003491 Skin Anatomy 0.000 claims description 15
- 238000007790 scraping Methods 0.000 claims description 7
- 210000004392 Genitalia Anatomy 0.000 claims description 3
- 210000003127 Knee Anatomy 0.000 claims description 3
- 210000003739 Neck Anatomy 0.000 claims description 3
- 210000000707 Wrist Anatomy 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000003247 decreasing Effects 0.000 abstract description 7
- 230000035515 penetration Effects 0.000 abstract description 4
- 230000036074 healthy skin Effects 0.000 abstract description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 45
- 210000002683 Foot Anatomy 0.000 description 15
- BJEPYKJPYRNKOW-UHFFFAOYSA-N Malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 15
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 15
- 229960004106 citric acid Drugs 0.000 description 15
- 235000015165 citric acid Nutrition 0.000 description 15
- 239000001630 malic acid Substances 0.000 description 15
- 229940099690 malic acid Drugs 0.000 description 15
- 235000011090 malic acid Nutrition 0.000 description 15
- 239000011975 tartaric acid Substances 0.000 description 15
- 229960001367 tartaric acid Drugs 0.000 description 15
- 235000002906 tartaric acid Nutrition 0.000 description 15
- 229960000448 Lactic acid Drugs 0.000 description 14
- 241000934136 Verruca Species 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 8
- 206010059313 Anogenital warts Diseases 0.000 description 7
- 241000701806 Human papillomavirus Species 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 229920000742 Cotton Polymers 0.000 description 4
- 210000004247 Hand Anatomy 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- 201000004201 anogenital venereal wart Diseases 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 201000004303 plantar wart Diseases 0.000 description 4
- 230000035943 smell Effects 0.000 description 4
- 208000000907 Condylomata Acuminata Diseases 0.000 description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 201000004196 common wart Diseases 0.000 description 3
- -1 ethyl lactate Chemical compound 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 230000003442 weekly Effects 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butanoic acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 240000002809 Lavandula angustifolia Species 0.000 description 2
- 235000003515 Lavandula officinalis Nutrition 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000000840 anti-viral Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 235000018219 lavender Nutrition 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissues Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-M (S)-lactate Chemical compound C[C@H](O)C([O-])=O JVTAAEKCZFNVCJ-REOHCLBHSA-M 0.000 description 1
- OMPIYDSYGYKWSG-UHFFFAOYSA-L 2-(2-ethoxy-2-oxoethyl)-2-hydroxybutanedioate Chemical compound CCOC(=O)CC(O)(C([O-])=O)CC([O-])=O OMPIYDSYGYKWSG-UHFFFAOYSA-L 0.000 description 1
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-Hydroxybutyric acid Chemical compound CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 description 1
- UQZPGHOJMQTOHB-UHFFFAOYSA-N 2-chloro-N-(2-chloroethyl)-N-ethylethanamine Chemical group ClCCN(CC)CCCl UQZPGHOJMQTOHB-UHFFFAOYSA-N 0.000 description 1
- DOSIONJFGDSKCQ-UHFFFAOYSA-N 3-amino-5-pyridin-4-yl-1H-pyridin-2-one;2-hydroxypropanoic acid Chemical compound CC(O)C(O)=O.N1C(=O)C(N)=CC(C=2C=CN=CC=2)=C1 DOSIONJFGDSKCQ-UHFFFAOYSA-N 0.000 description 1
- ZUDZWKJBYZAGBS-UHFFFAOYSA-M 4-ethoxy-2,3-dihydroxy-4-oxobutanoate Chemical compound CCOC(=O)C(O)C(O)C([O-])=O ZUDZWKJBYZAGBS-UHFFFAOYSA-M 0.000 description 1
- 229960000583 Acetic Acid Drugs 0.000 description 1
- 241000722891 Callitris Species 0.000 description 1
- 241001585562 Callitris columellaris Species 0.000 description 1
- YSAVZVORKRDODB-WDSKDSINSA-N Diethyl tartrate Chemical compound CCOC(=O)[C@@H](O)[C@H](O)C(=O)OCC YSAVZVORKRDODB-WDSKDSINSA-N 0.000 description 1
- 229940105553 Duofilm Drugs 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229940116871 L-lactate Drugs 0.000 description 1
- 229940001447 Lactate Drugs 0.000 description 1
- 235000010701 Lavanda vera Nutrition 0.000 description 1
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 1
- 210000002414 Leg Anatomy 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 241000378467 Melaleuca Species 0.000 description 1
- 241000366182 Melaleuca alternifolia Species 0.000 description 1
- 229940095574 Propionic acid Drugs 0.000 description 1
- 229940005581 Sodium Lactate Drugs 0.000 description 1
- NGSFWBMYFKHRBD-UHFFFAOYSA-M Sodium lactate Chemical compound [Na+].CC(O)C([O-])=O NGSFWBMYFKHRBD-UHFFFAOYSA-M 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- HGINCPLSRVDWNT-UHFFFAOYSA-N acrylaldehyde Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001746 carotenes Chemical class 0.000 description 1
- 235000005473 carotenes Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- VKNUORWMCINMRB-UHFFFAOYSA-N diethyl malate Chemical compound CCOC(=O)CC(O)C(=O)OCC VKNUORWMCINMRB-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing Effects 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000002349 favourable Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000001102 lavandula vera Substances 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003000 nontoxic Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000546 pharmaceutic aid Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- CZPZWMPYEINMCF-UHFFFAOYSA-N propaneperoxoic acid Chemical compound CCC(=O)OO CZPZWMPYEINMCF-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- NBBJYMSMWIIQGU-UHFFFAOYSA-N propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100000486 side effect Toxicity 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000014599 transmission of virus Effects 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 200000000019 wound Diseases 0.000 description 1
Abstract
The present invention concerns the use of formic acid and at least one C1-C4 alkyl ester of lactic acid, preferably ethyl lactate, for the manufacture of a composition for the topical treatment of warts. The inclusion in the composition of at least one C1-C4 alkyl ester of lactic acid, preferably ethyl lactate, reduces the contact angle of the composition, i.e. reduces the surface tension. Decreased contact angle makes it easier for the composition to adhere to warts, and following to be absorbed by warts, i.e. improving the penetration of the composition of the invention. Additionally, reduced surface tension makes it easier to apply the composition in the adequate amount, with reduced risk of inadvertently smearing composition on adjacent, healthy skin. hyl lactate, reduces the contact angle of the composition, i.e. reduces the surface tension. Decreased contact angle makes it easier for the composition to adhere to warts, and following to be absorbed by warts, i.e. improving the penetration of the composition of the invention. Additionally, reduced surface tension makes it easier to apply the composition in the adequate amount, with reduced risk of inadvertently smearing composition on adjacent, healthy skin.
Description
COMPOSITION FOR TREATMENT OF WARTS
The present invention relates to a composition for the treatment of warts. In
particular, it concerns a composition for the topical treatment of warts in
mammals, such as humans.
Technical Background
The European patent 1143966 B1 describes the use of a preparation
comprising formic acid as an active ingredient for the manufacture of a
medicament for the treatment of warts caused by virus in a mammal, by
topical administration of the medicament on the affected area. The patent
teaches that the wart should be softened with hot water and that, if
necessary, hard skin covering the wart should be scraped of, before
treatment with formic acid.
Bhat et al. (“Topical formic acid puncture technique for the treatment of
common warts”, International Journal of Dermatology 2001, 40, 415-419)
discloses a topical application/needle puncture technique for the treatment of
warts.
Summary of the invention
The needle puncture technique has been regarded as the best wart treatment
using formic acid, as the puncture technique has hitherto provided the best
reproducible results.
There is a continued need for alternative means for the treatment of warts.
Several demands may be put on such means. It may preferably be
inexpensive, easy to manufacture, storage stable, effective, and should work
shortly after application, allowing warts to be eradicated within a short time
span. In addition, it should preferably be easy to apply without the aid from
medical expertise, non-toxic, and not be associated with discomfort for the
patient, i.e. it should not have a repulsive smell or be painful for the patient
during or after administration.
Some patients complain that acid based means for the topical treatment of
warts have low efficacy, take several weeks to act, are foul-smelling and may
be painful to apply.
There is a need for a composition which a patient may apply without the need
of any preparatory steps, before application of the composition on the warts.
It has surprisingly been identified that a composition comprising formic acid
and at least one C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid, or
citric acid, preferably ethyl lactate, has particular advantages for the topical
treatment of warts.
In particular, it has surprisingly been identified that the inclusion in the
composition of at least one C1-C4 alkyl ester of lactic acid, malic acid, tartaric
acid, or citric acid, preferably ethyl lactate, provides the same effect as using
the puncture technique for improving the effect of the acid on the warts.
It has been identified that it may not be necessary to remove hard skin
covering warts by use of a composition according to the present invention.
Further, it has surprisingly been identified that the high concentrations
proposed by the prior art may not be necessary in all cases, by using a
composition according to the present invention.
Experiments indicate that the inclusion in the composition of at least one C1-
C4 alkyl ester of lactic acid, malic acid, tartaric acid, or citric acid, preferably
ethyl lactate, reduces the contact angle of the composition, i.e. reduces the
surface tension. Without being bound by any theory, it may be speculated that
the number or strengths of hydrogen bonds in the composition is decreased
by the inclusion of one of the alkyl esters, such as ethyl lactate, thereby
decreasing the contact angle. Inclusion of water and/or alcohol may increase
the contact angle. Decreased contact angle makes it easier for the
composition to adhere to warts, and following to be absorbed by warts, i.e.
improving the penetration of the composition of the invention. Improved
penetration may further emphasize any antiviral effects of formic acid.
Additionally, reduced surface tension makes it easier to apply the composition
in the adequate amount, with reduced risk of inadvertently smearing
composition on adjacent, healthy skin. The reduced surface tension may
easily be tested by placing a drop of the composition of the invention on a
plate, and comparing with a drop of a composition of the prior art, such as a
composition comprising water and formic acid.
It has been realized by the inventor that it may be beneficial to distinguish
between soft warts and hard warts.
In particular, it has been identified that a composition with a lower content of
acid may be preferable in the treatment of soft warts, as a composition with
higher content of acid is more likely to give damages upon accidental
application on the surrounding skin. Further, it has been discovered that the
use of a composition with high content of acid on soft warts gave unwanted
side effects in some cases. However, higher content of acids are particularly
suitable for hard wards, which are difficult to remove.
The exact mechanism of action of formic acid in relation to the treatment of
warts is not known. Dehydration with subsequent destruction of wart infected
tissue has been proposed. In addition, formic acid may prevent virus particles
from attaching to healthy cells, thereby inhibiting viral transmission.
It may be speculated that there is a synergistic effect between formic acid and
at least one C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid, or citric
acid, such as ethyl lactate, providing a strong effect against warts. Without
being bound by any theory, the inventor of the present invention speculate
that formic acid in itself acts as an active ingredient, while e.g. ethyl lactate
acts as an active carrier, allowing the concentration of acid to be kept locally
sufficiently low to impede irritation for the patient. It is additionally speculated
that such a carrier allow the acid to penetrate deeper into the warts. Further,
the inventor speculates that formic acid and ethyl lactate in the presence of
water may react to form lactic acid, which independently acts as an active
ingredient.
Aspects and embodiments of the present invention are provided here. It will
be clear for the person skilled in the art that these may be combined.
Described herein is the use of formic acid and at least one C1-C4 alkyl ester
of lactic acid, malic acid, tartaric acid, or citric acid, preferably ethyl lactate, for
the manufacture of a composition for the topical treatment of warts. According
to an aspect, the invention provides the use of formic acid and at least one
C1-C4 alkyl ester of lactic acid, preferably ethyl lactate, for the manufacture of
a composition for the topical treatment of warts.
Described herein is the use of a composition comprising formic acid and at
least one C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid, or citric
acid, preferably ethyl lactate, for the topical treatment of warts.
Described herein is a pharmaceutical composition comprising formic acid and
at least one C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid, or citric
acid, preferably ethyl lactate, for the treatment of warts.
Described herein is a pharmaceutical composition for the topical treatment of
warts, comprising formic acid and being free of water and/or alcohol.
Described herein is a method of treating warts, comprising topically
administering a composition comprising formic acid and at least one C1-C4
alkyl ester of lactic acid, malic acid, tartaric acid, or citric acid, preferably ethyl
lactate, to a patient in need thereof.
According to yet another aspect, the invention concerns a pen, comprising a
composition according to the invention, for topical administration of a
composition according to the invention. A pen has shown to be particularly
useful for the application of a pharmaceutical composition according to the
invention, as exact control of the precise location of application of the
composition may be achieved by the topical application on a wart with the
pen. Further, the composition may be rubbed or massaged into a wart with
the tip of the pen.
Detailed Disclosure
The invention concerns a composition comprising formic acid and at least one
C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid, or citric acid,
preferably ethyl lactate. Such a composition may be used for the treatment of
warts, typically by topical treatment of warts.
Described herein is a composition comprising formic acid and at least one
C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid, citric acid, or a
mixture of any of these, for use in topical treatment of warts.
Such a composition may be applied with a soft cotton pad or cotton stick
swab, or a pen, i.e. without scraping skin of the warts and without the need of
puncturing the warts before application. Scraping skin of the warts and/or
puncturing the warts may be associated with pain and should thus be
avoided. Avoiding scraping and/or puncturing may improve patient
compliance.
In one embodiment of this aspect, said at least one C1-C4 alkyl ester is ethyl
lactate.
Ethyl lactate, also known as lactic acid ethyl ester, is found naturally, and
carries a pleasant odor. Ethyl lactate may be produced from biological
sources, e.g. by fermentation. Ethyl lactate may be either the levo (S) or
dextro (R) form or a mixture of the two. Industrially produced ethyl lactate may
consist of a racemic mixture of levo and dextro forms.
According to an embodiment, ethyl lactate used in the present invention is a
racemic mixture.
According to another embodiment, ethyl lactate used in the present invention
is ethyl (-)-L-lactate, or more than 50% of the ethyl lactate is ethyl (-)-L-
lactate. This may be obtained by using ethyl lactate derived from natural
sources. According to a preferred embodiment ethyl lactate is ethyl-S(-)
hydroxy propanoate. Preferably it is obtained by fermentation from sugar.
Compositions according to the present invention preferably comprise ethyl
lactate. According to an embodiment it is contemplated that this ingredient
may be partly or fully substituted with at least one C1-C4 alkyl ester of lactic
acid, malic acid, tartaric acid, citric acid, or a mixture of any of these. The
inventor of the present invention speculates that these alkyl esters may have
anti-viral effect and/or suitable transport enhancing properties. Among the C1-
C4 of relevance for the present invention may be mentioned methyl, ethyl, n-
propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl esters. If suitable,
any or all carboxy groups may be esterified. Monoalkyl, dialkyl and/or trialkyl
esters may be suitable. Preferred esters are ethyl esters, further preferred are
isopropyl esters. In addition to ethyl lactate, further preferred compounds are
diethyl malate, diisopropyl malate, monoethyl tartrate, diethyl tartrate,
monoethyl citrate and triethyl citrate.
According to an embodiment it is further contemplated that ethyl lactate may
be partly or fully substituted with other ingredients with similar properties,
such as lactic acid, preferably L-lactate, malic acid, tartaric acid, citric acid,
acetic acid, glycolic acid, propionic acid, 3-hydroxypropanoic acid, malonic
acid, butyric acid, hydroxybutyric acid, 1-propanol, 2-propanol,
propionaldehyde, acrolein or sodium lactate, or a mixture of any of these.
A range of types of warts has been identified, varying in shape and site
affected, as well as the type of human papilloma virus involved. These
include, but are not limited to: common wart (Verruca vulgaris), flat wart
(Verruca plana), filiform or digitate wart, plantar wart (Verruca Pedis), mosaic
wart, genital wart (veneral wart, Condyloma acuminatum, Verruca
acuminate), and periungal wart.
According to an embodiment, the invention concerns the use of a composition
according to the invention, wherein the warts are selected among the group
consisting of common wart (Verruca vulgaris), flat wart (Verruca plana),
filiform or digitate wart, plantar wart (Verruca Pedis), mosaic wart, genital wart
(veneral wart, Condyloma acuminatum, Verruca acuminate), and periungal
wart.
According to an embodiment, the invention concerns the use of a composition
of the invention, wherein the warts are common warts.
According to an embodiment, the invention concerns the use of a composition
of the invention, wherein the warts are plantar or flat warts.
According to an embodiment, the invention concerns the use of a composition
of the invention, wherein the warts are filiform or digitate warts.
According to an embodiment, the invention concerns the use of a composition
of the invention, wherein the warts are caused by human papillomavirus
(HPV), such as a genotype of HPV causing warts selected among the group
consisting of verruca vulgaris, verruca plantaris, verruca plana, and
condyloma acuminatum.
According to an embodiment, the invention concerns the use of a composition
of the invention, wherein the warts are caused by human papillomavirus
(HPV), such as a type of HPV selected among the group consisting of the
types 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 26, 27, 28, 29, 31, 32,
33, 35, 39, 40, 42, 43, 44, 45, 49, 51, 52, 53, 54, 56, 57, 58, 59, 61, 63, 66,
68, 72, 73, 81, 82, and 89.
According to an embodiment, the invention concerns a composition for
application directly on the warts without puncturing the warts or scraping skin
of the warts.
According to an embodiment, the invention concerns a composition for
application with a soft pen or cotton pad.
According to an embodiment, the invention concerns a composition, wherein
the total amount (w/w) of formic acid in the composition is 1- 95%, preferably
2 – 90%, more preferred 3 – 85%, preferably 5 – 80%, more preferred 10 –
70%, preferably 15 – 65%, more preferably 20 – 60%, more preferred 25 –
50%, preferably 30-40%, more preferred 30-35%.
According to an embodiment the invention concerns a composition, wherein
the total amount (w/w) of formic acid in the composition is 60 – 95%, more
preferred 70 – 90%, preferably 80 – 85%. Such a composition is particularly
preferred for use on hard warts. Weekly application is particularly preferred
for such a composition.
According to an embodiment the invention concerns a composition for use,
wherein the total amount (w/w) of formic acid in the composition is 60 – 95%,
more preferred 70 – 90%, preferably 80 – 85%.
According to an embodiment the invention concerns a composition for use,
wherein said composition comprises 80 – 85% formic acid (w/w); 15 – 20%
ethyl lactate (w/w); and substantially no water and/or alcohol.
According to an embodiment the invention concerns such a composition, for
wherein said composition is for use on hard warts.
According to an embodiment the invention concerns such a composition, for
use on the palm or the foot sole.
According to an embodiment the invention concerns such a composition,
wherein the warts are selected among the group consisting of common wart
(Verruca vulgaris), plantar wart (Verruca pedis), and mosaic wart.
Alternatively, according to an embodiment the invention concerns a
composition, wherein the total amount (w/w) of formic acid in the composition
is 10 – 60%, more preferred 15 – 50%, preferably 20 – 40%, more preferred
– 35%. Lower percentage of formic acid improves the smell of the
composition and tends to increase patient compliance. This composition is
particularly preferred for use on soft warts. Daily application is particularly
preferred for this composition.
Described herein is a composition for use, wherein said composition
comprises 30 – 35% formic acid (w/w); 65 – 70% ethyl lactate (w/w); and
substantially no water and/or alcohol. This composition is particularly useful
for use on soft warts.
According to an embodiment the invention concerns this composition, for use
on other sites than the palm or the foot sole.
According to an embodiment the invention concerns this composition for use
on the back of the foot, the back of the hand, the face, neck, wrists, knees or
genitalia.
According to an embodiment the invention concerns this composition,
wherein the warts are selected among the group consisting of flat wart
(Verruca plana), filiform or digitate wart, genital wart (veneral wart,
Condyloma acuminatum, Verruca acuminate), and periungal wart.
According to an embodiment, the invention concerns a composition, wherein
the total amount (w/w) of alkyl ester, such as ethyl lactate, in the composition
is 1 – 95%, preferably 2 – 90%, more preferred 3 – 85%, preferably 5 – 80%,
more preferred 10 – 70%, preferably 15 – 65%, more preferably 20 – 60%,
more preferred 25 – 50%, preferably 30 – 40%, more preferred 30 – 35%.
According to an embodiment, the invention concerns a composition, wherein
the total amount (w/w) of said C1-C4 alkyl ester, such as ethyl lactate, in the
composition is 40 – 90%, more preferred 50 – 85%, preferably 60 – 80%,
more preferred 65 – 70%.
According to an embodiment, the invention concerns a composition, wherein
the total amount (w/w) of said C1-C4 alkyl ester, such as ethyl lactate, in the
composition is 2 – 50%, more preferred 3 – 40%, preferably 5 – 35%, more
preferred 10 – 30%, preferably 15 – 20%.
According to an embodiment, the invention concerns a composition, wherein
the composition comprises lactic acid, preferably wherein the total amount
(w/w) of lactic acid in the composition is 2 – 90%, more preferred 3 – 85%,
preferably 5 – 80%, more preferred 10 – 70%, preferably 15 – 65%, more
preferably 20 – 60%, more preferred 30 – 50%, preferably 35 – 40%.
According to an embodiment, the invention concerns a composition, wherein
the total combined amount of formic acid and C1-C4 alkyl ester, such as ethyl
lactate, in the composition is at least 60%, more preferred at least 70%,
preferably at least 80%, more preferred at least 90%, preferably at least 95%,
more preferably at least 97%, more preferred at least 98%, preferably at least
99%, more preferred 100% (w/w).
According to a further embodiment of the present invention, pharmaceutically
acceptable carriers, such as water, oil, glycerol, alcohol or mixtures thereof,
can be included in a composition according to the invention, e.g. to achieve a
further softening effect on and around the warts.
According to an embodiment, a composition according to the invention may
comprise additional active ingredients or excipients. Examples comprise, but
are not limited to, Callitris Intratropica, Lavandula Angustifolia, Melaleuca
Alternifolia, lemon oil, and mixtures of any of these. The person skilled in the
art is familiar with additional pharmaceutically acceptable excipients which
may be combined with the present invention.
According to an embodiment, a composition according to the invention may
be made substantially free of water and/or ethanol.
According to an embodiment, the invention concerns a composition for the
topical treatment of warts comprising formic acid as an active ingredient, and
less than 15%, preferably less than 10%, more preferred less than 5%,
preferably less than 3%, more preferred substantially no water and/or alcohol
such as ethanol.
According to an embodiment, the invention concerns a composition for the
topical treatment of warts comprising formic acid as an active ingredient, such
as a composition according to the invention, and further comprising at least
one colorant, e.g. a dye or a pigment, such as carotene. This embodiment
may facilitate correct application on warts, and avoid application on
surrounding tissue and skin. Particularly preferred is a colorant with a discrete
color, or a color, which vanishes from the warts after application. This may
improve patient compliance.
According to an embodiment, a composition according to the invention may
be in the form of an emulsion, cream, paste, ointment, lotion, suspension, gel,
spray, and/or together with topical carriers suitable for the treatment.
According to an embodiment, a composition according to the invention may
be for human use or for veterinary use.
According to an embodiment, the invention concerns a pharmaceutical
composition for medical use.
According to an embodiment, the invention concerns a pharmaceutical
composition comprising formic acid and at least one C1-C4 alkyl ester of
lactic acid, malic acid, tartaric acid, citric acid, or a mixture of any of these,
preferably ethyl lactate; preferably for the treatment of warts.
According to an embodiment, the invention concerns use of formic acid and at
least one C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid, citric acid,
or a mixture of any of these, for the manufacture of a composition according
to the invention, such as for the topical treatment of warts.
Described herein is a method of treating warts, comprising topically
administering a composition comprising formic acid and at least one C1-C4
alkyl ester of lactic acid, malic acid, tartaric acid, citric acid, or a mixture of
any of these, to a patient in need thereof.
In one embodiment, said at least one C1-C4 alkyl ester is ethyl lactate.
In another embodiment, said composition is applied directly on the warts
without puncturing the warts or scraping skin of the warts.
In another embodiment, the total amount (w/w) of formic acid in the
composition is 60 – 95%, more preferred 70 – 90%, preferably 80 – 85%.
In another embodiment, the composition comprises 80 – 85%; of formic acid
(w/w); 15 – 20% ethyl lactate (w/w); and substantially no water and/or alcohol.
Said composition may be applied on hard warts. Typically, said composition is
applied on the palm or the foot sole.
In another embodiment, the total amount (w/w) of formic acid in the
composition is 10 – 60%, more preferred 15 – 50%, preferably 20 – 40%,
more preferred 30 – 35%.
In an alternative embodiment, the composition comprises 30 – 35% (w/w) of
formic acid; 65 – 70% (w/w) of ethyl lactate; and substantially no water and/or
alcohol. Said composition may be applied on soft warts. Said composition
may be applied on other sites than the palm or the foot sole, such as on the
back of the foot, the back of the hand, the face, neck, wrists, knees or
genitalia. In these compositions, there may be less than 15%, preferably less
than 10%, more preferred less than 5%, preferably less than 3%, more
preferred substantially no water and/or alcohol such as ethanol.
Described herein is a composition comprising 30 – 35% formic acid (w/w); 65
– 70% ethyl lactate (w/w); and substantially no water and/or alcohol.
Described herein is a composition comprising 80 – 85% formic acid (w/w); 15
– 20% ethyl lactate (w/w); and substantially no water and/or alcohol.
All proportions and percentages are in weight/weight unless otherwise
mentioned.
All cited references are incorporated by reference.
The accompanying Examples are provided to explain rather than limit the
present invention. It will be clear to the person skilled in the art that aspects,
embodiments and claims of the present invention may be combined.
Examples
Example 1
Three different compositions were compared by topical application on warts
on human subjects.
A first composition (A) was prepared by mixing 30% formic acid with 70%
ethyl lactate (w/w).
A second composition (B) was prepared by mixing 85% formic acid with 15%
ethyl lactate (w/w).
The third composition (C) was GSK Duofilm, indicated to comprise 16.7%
salicylic acid and 16.7% lactic acid.
90 patients with warts were divided into three groups of 30 patients. The
groups received treatment as follows:
Group I: Composition (A). The composition was applied once daily for a
maximum of 12 weeks or until the warts were removed.
Group II: Composition (B). The composition was applied once weekly for a
maximum of 12 weeks or until the warts were removed.
Group III: Composition (C). The composition was applied once daily for a
maximum of 12 weeks or until the warts were removed.
Number of patients Group I Group II Group III
Dropped out 6 7 8
Decreased 3 1 2
Failure 3 2 5
Resolved 18 20 15
Sum 30 30 30
“Dropped out” refers to the patients, who did not complete the study, i.e. failed
to show up until completion of the study.
Patients Group I Group II Group III
Dropped out 20% 23% 27%
Among non-
dropped out
Group I Group II Group III
patients
Decreased 13% 4% 9%
Failure 13% 9% 23%
Resolved 75% 87% 68%
Number of warts Group I Group II Group III
Resolution 50% 90% 45%
In general, higher formic acid concentration led to higher efficacy. However,
complaints were also increasing due to pain upon application of the
compositions with higher formic acid contents. It was found that composition
(A) was especially suitable for treating warts on other places than the feet and
hands, such as other places than the palm and the foot sole, while
composition (B) was especially suitable for treating warts on feet and hands,
particularly on the palm and the foot sole. Of the three tested compositions,
composition (C) led to the highest drop-out rate, the highest failure rate
among the patients, and the lowest percentage of resolved warts.
Comparison Example 1
A mixture comprising 85% formic acid and 15% water was applied on warts,
using a puncture technique.
The results using this puncture technique was comparable to the effect
obtained by using the second mixture (B) according to the invention.
However, the use of the second mixture (B) did not necessitate the use of a
puncture technique, as the second composition (B) was applied directly on
the warts.
Comparison Example 2
A mixture comprising 85% formic acid and 15% water was applied on the skin
of a human male. The mixture was foul smelling and painful upon application.
Contemplated Compositions of the Invention
The compositions of Table 1 have been made or are contemplated. The
compositions may be manufactured by mixing the ingredients at room
temperature.
The compositions may be applied on a wart as a drop, with a cotton stick or
with a pen comprising the composition.
Table 1
Composition Formi Ethyl Lactic Lavender Callitris Melaleuca Aqua Glycerol Total
No. c acid lactate acid Oil intratropica alternifolia
oil oil
1 85% 15% 100%
2 33% 56% 10% 1% 100%
3 3% 87% 10% 100%
4 100%
% 80% 10%
100%
50% 30% 20%
6 100%
50% 15% 30% 1% 1% 1% 1% 1%
7 100%
% 70% 10%
100%
40% 35% 20% 4% 1%
9 100%
% 40% 5% 10% 1% 4% 5%
100%
60% 20% 5% 10% 5%
11 100%
% 30% 10% 15% 10% 15%
12 100%
80% 15% 3% 2%
13 100%
75% 5% 15% 5%
14 100%
70% 25% 2% 2% 1%
100%
% 25% 40% 5%
100%
45% 15% 40%
17 100%
% 90%
18 100%
% 80% 5%
19 100%
% 50% 10% 5%
100%
% 15% 50% 1% 1% 1% 1% 1%
21 100%
40% 50% 10%
22 100%
% 50% 25%
23 100%
14% 70% 10% 1% 5%
24 100%
% 65%
100%
% 70%
Measurement of Contact Angle
Measurements of the contact angle of mixtures of a) formic acid and water;
and b) formic acid and ethyl lactate were conducted according to the following
protocol:
1) Coverslip cleaned with methanol were washed with H2O and dried with N2.
2) The liquid mixtures were mixed on a rotation table for 10 min.
3) Using 2 coverslips for each comparison, three droplets of each of the
samples are added onto each of the two coverslips.
Each solution (mixture) was measured on two distinct surfaces (3 drops on
each surface). From the contact angle studies a significant difference
between the samples was observed. The results are provided in Table 2
below.
Table 2
Average Measured Contact + water to 100% (w/w) +ethyl lactate to 100% (w/w)
Angles of Mixtures
% formic acid 31 16
85% formic acid 18 10
Conclusions
Preliminary experiments indicate selected compositions according to the
invention may in favorable cases completely eradicate a treated wart within 2
– 3 days upon daily topical administration. Other cases may require longer
time, such as 1, 2 or 3 weeks. Particular success has been achieved with
filiform warts in the face of a patient. In contrast, the mixture of the
Comparison Example 2 took several weeks, and as an average about a
month, before the warts were removed from the hands and feet of the
patients. No success with the removal of warts in the face of a patient was
reported with the mixture of the Comparison Example. Further, some subjects
have complained about pain upon application of the Comparison Example 2,
e.g. if this mixture was applied on skin.
Lower concentrations of formic acid tend to remove the smell and the pain
associated with application of a wart mixture comprising formic acid. Earlier, it
has been conventional wisdom that formic acid should be present in a high
concentration, such as about 85%, to be effective against warts. The present
invention appears to allow the treatment of warts using lower concentrations
of formic acid. Lower concentrations allow more frequent, such as daily,
application of the composition, and thus the concentration of active
ingredients in situ may be kept approximately constant as compared to the
situation where a composition is applied on a weekly basis. High
concentration of formic acid is associated with the disadvantage of pain and
creation of wounds upon accidental application on the skin surrounding a
wart. Thus, high concentration of formic acid usually require longer intervals
between application, as the skin needs time to reconstitute between
treatments.
Further, no pretreatment with hot water or scraping of hard skin appeared
necessary. In addition, as the smell was not repulsive as opposed to the
Comparison Example, a composition of the present invention could readily be
applied to the face, arms, legs and body of the patient with good compliance.
A composition according to the invention could be applied to other parts of the
skin, such as the hands and feet of the patients, with similar good
compliance.
Claims (29)
1. Use of formic acid and at least one C1-C4 alkyl ester of lactic acid, for the manufacture of a composition for the topical treatment of warts.
2. The use of claim 1, wherein said at least one C1-C4 alkyl ester is ethyl 5 lactate.
3. The use of claim 1, wherein said composition is to be applied directly on the warts without puncturing the warts or scraping skin of the warts.
4. The use of claim 1, wherein the total amount (w/w) of formic acid in the composition is 1-95%. 10
5. The use of claim 4, wherein the total amount (w/w) of formic acid in the composition is 60 – 95%.
6. The use of claim 5, wherein the total amount (w/w) of formic acid in the composition is 70 – 90%.
7. The use of claim 6, wherein the total amount (w/w) of formic acid in the 15 composition is 80 – 85%.
8. The use of claim 1, wherein said composition comprises 80 – 85%; of formic acid (w/w); 15 – 20% ethyl lactate (w/w); and substantially no water and/or alcohol.
9. The use of claim 8, wherein said warts are hard warts. 20
10. The use of claim 8 or 9, wherein said warts are on the palm or the foot sole.
11. The use of claim 1, wherein the total amount (w/w) of formic acid in the composition is 10 – 60%.
12. The use of claim 11, wherein the total amount (w/w) of formic acid in the composition is 15 – 50%.
13. The use of claim 12, wherein the total amount (w/w) of formic acid in the composition is 20 – 40%. 5
14. The use of claim 13, wherein the total amount (w/w) of formic acid in the composition is 30 – 35%.
15. The use of claim 1, wherein said composition comprises 30 – 35% (w/w) of formic acid; 65 – 70% (w/w) of ethyl lactate; and substantially no water and/or alcohol. 10
16. The use of claim 15, wherein said warts are soft warts.
17. The use of claim 15 or 16, wherein said warts are on other sites than the palm or the foot sole.
18. The use of claim 15 or 16, wherein said warts are on the back of the foot, the back of the hand, the face, neck, wrists, knees or genitalia. 15
19. The use of claim 1, wherein, in the composition, there is less than 15% water and/or alcohol.
20. The use of claim 19, wherein the alcohol is ethanol.
21. The use of claim 19 or 20, wherein, in the composition, there is less than 10% water and/or alcohol. 20
22. The use of claim 21, wherein, in the composition, there is less than 5% water and/or alcohol.
23. The use of claim 22, wherein, in the composition, there is less than 3% water and/or alcohol.
24. The use of claim 23, wherein, in the composition, there is substantially no water and/or alcohol.
25. The use of claim 1, wherein said composition comprises about 30 formic acid (w/w); and about 70% ethyl lactate (w/w). 5
26. The use of claim 1, wherein said composition comprises about 85% formic acid (w/w); and about 15% ethyl lactate (w/w).
27. Pen for topical administration, comprising a composition comprising formic acid and at least one C1-C4 alkyl ester of lactic acid, wherein said composition is as defined in any one of claims 1-26. 10
28. Use of any one of claims 1-26 substantially as herein described with reference to any example thereof.
29. Pen of claim 27 substantially as herein described with reference to any example thereof.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/SE2012/050566 WO2013180606A1 (en) | 2012-05-28 | 2012-05-28 | Composition for treatment of warts |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ702424A NZ702424A (en) | 2017-02-24 |
NZ702424B2 true NZ702424B2 (en) | 2017-05-25 |
Family
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