WO1998017265A1 - Pharmaceutical composition containing tromethamine for the topical treatment of acne vulgaris - Google Patents
Pharmaceutical composition containing tromethamine for the topical treatment of acne vulgaris Download PDFInfo
- Publication number
- WO1998017265A1 WO1998017265A1 PCT/IT1997/000239 IT9700239W WO9817265A1 WO 1998017265 A1 WO1998017265 A1 WO 1998017265A1 IT 9700239 W IT9700239 W IT 9700239W WO 9817265 A1 WO9817265 A1 WO 9817265A1
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- WIPO (PCT)
- Prior art keywords
- tromethamine
- realization
- composition according
- grams
- stearyl
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
Definitions
- the present invention concerns a pharmaceutical composition containing tromethamine for the topical treatment of acne vulgaris.
- Tromethamine behaves as a weak base characterized by a significant buffer action.
- a 0.3 molar solution (3.6% solution - 36 g/litre) is iso-osmolar with human plasma and has a pH of about 8.
- tromethamine has been employed in the synthesis of surface-active agents and of vulcanisation accelerators. In cosmetics, it is used as an emulsifying agent for creams and lotions. In medical therapy tromethamine is used in the treatment of metabolic, respiratory, diabetic and post-operative acidosis; in acidosis during the cardiopulmonary bypass, in heart failure and shock. In all these therapeutic uses, tromethamine is employed in the form of a 0.3 molar watery solution.
- Acne vulgaris is one of the most common dermatological affection that strikes 25% of the youth between 12 and 20 years in variable measure. As in its most serious forms, which are not infrequent, acne vulgaris may cause disfiguring scars, it is in fact a disease with large psychical implications that may result in social maladjustment and self-isolation.
- the topical therapy is based on the use of compounds against seborrhoea compositions with keratolytic action (benzoyl peroxide) , with a basis of retinoic acid, estrogens and topical corticosteroids .
- Topical preparations against seborrhoea in general are available in a huge variety of lotions, creams, powders containing sulphur, salicylic acid and resorcinol.
- the majority of these products are irritant when applied onto the skin, and the best results are obtained when they are used with they produce a non- damaging exsiccation and an exfoliation of the affected skin.
- a too limited use offers a very limited advantage, while an excessive use may be the cause of further lesions and pain. All these products might induce further seborrhoea.
- Benzoyl peroxide acts as an exfoliating and a keratolytic agent. Therapeutic results are not obtained before 5-6 weeks. This treatment may produce skin irritation at various degrees and eczema.
- Retinoic acids acts against the creation of comedones.
- the greatest handicap of this product is its irritating action that, during the first month of treatment or even further, may cause a deterioration of the lesions, with erythema and desquamation, and such collateral effects might lead to a suspension of the therapy.
- the effectiveness of the treatment with chemotherapeutic agents and antibiotics is debatable, as there might occur photo- sensitization and modification of the bacterial flora.
- the hormonic therapy has several drawbacks. First of all, male patients are excluded from the treatment; secondly, therapeutic effects are detectable only after months; finally, the best results are obtained using preparations with a higher level of estrogens, which yet present the greatest risks of thrombosis and embolism. Usually the hormonic therapy is employed in young female patients with acne clearly becoming acute in pre-menstrual periods.
- the present invention derives from the discovery that tromethamine and its pharmacologically acceptable salts, such as acetate, carbonate, citrate, phosphate, succinate and sulfate, administered in topical applications, are extremely effective anti-acne agents, not presenting the considerable side effects of known medicines .
- a pharmaceutical composition according to above scientific and experimental discovery comprising tromethamine and/or its pharmacologically acceptable salts in preparations for topical use such as creams, emulsions, solutions, lotions, in spray containers and similar.
- compositions are given per 100 g of their formulation.
- Spray composition tromethamine gr. 3.60 citric acid " 0.65 cetyl-stearyl-ethoxylate alcohol " 2.00 water " 83.70 freon 12 - Freon 114 (15/85) " 10.00
- Cream composition tromethamine gr. 3.60 citric acid " 0.65 silicon oil “ 0.15 soya lecithin “ 1.00 sodium stearyl lactilate “ 1.50 cetyl-stearyl-ethoxylate alcohol “ 14.00 propylene glycol “ 4.00 glycerin “ 2.00 nipasept " 0.15 water " 73.00
- 0.3 molar watery solutions may also be used.
- composition according to the present invention has been tested, using a 3.6% tromethamine solution (thamesol of Baxter hydroxymethyl - aminomethane 0.3 M - Acetic acid 0.1
- the clinical varieties treated were mixed forms of acne microcystica-comedonica and papulo-pustulosa, with a wide range of seriousness and extension of skin lesions.
- the medication On the dry face, the medication is applied and the skin is gently rubbed with wads watered with abundant tromethamine solution on all the points concerned.
- the application for a few minutes of a pledget soaked with solution has proved to be effective; the skin may dry at ambient air.
- the skin shows a definitely less greasy appearance; its surface is smoother and more regular; its colour is clearer and more uniform.
- the results further improve with a total "restitutio ad integrum" of the dermal tissue.
- tromethamine and its pharmacologically acceptable salts perform a progressive and constant therapeutical action in the topical treatment of acne vulgaris .
- the first event is shown by a rapid halt to the evolution of cutaneous lesions, followed by a constant regression, up to the complete remission, of the objective symptomatology. Such an effect is most evident towards the inflammatory component.
- the rectification of the abnormally lowered pH may determine the inhibition of those enzymatic activities (in particular, phospholipases) with an optimum in acid media (pH 5-6) , which give rise to the liberation of free fat acids.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
The pharmaceutical composition of tromethamine allows a topical treatment of acne vulgaris by means of the realization of creams, milks, lotions and similar, containing from 1 to 10 grams of tromethamine per 100 grams of product.
Description
PHARMACEUTICAL COMPOSITION CONTAINING TROMETHAMINE FOR THE TOPICAL TREATMENT OF ACNE VULGARIS
The present invention concerns a pharmaceutical composition containing tromethamine for the topical treatment of acne vulgaris.
It is known that tromethamine, 2 - amino - 2 (hydroxymethyl) propane 1,3 - diol, is an amino-alcohol whose formula is
HO - H2C
\ HO - H2C - C - NH2
/ HO - H2C
Tromethamine behaves as a weak base characterized by a significant buffer action. A 0.3 molar solution (3.6% solution - 36 g/litre) is iso-osmolar with human plasma and has a pH of about 8.
Up to now tromethamine has been employed in the synthesis of surface-active agents and of vulcanisation accelerators. In cosmetics, it is used as an emulsifying agent for creams and lotions. In medical therapy tromethamine is used in the treatment of metabolic, respiratory, diabetic and post-operative acidosis; in acidosis during the cardiopulmonary
bypass, in heart failure and shock. In all these therapeutic uses, tromethamine is employed in the form of a 0.3 molar watery solution. Commercial products are in the form of bottles containing 100 ml of a solution of 3.6 g of tromethamine and 0.6 g of glacial acetic acid in water, or boxes containing a lyophilized mixture of tromethamine, sodium chloride and potassium chloride, whose injectable solutions are prepared extempore.
There is no relationship between the therapeutic use of tromethamine in the treatment of above mentioned acidosis' and the treatment of Acne Vulgaris. Furthermore, tromethamine has never been used in therapy in topical applications.
Acne vulgaris is one of the most common dermatological affection that strikes 25% of the youth between 12 and 20 years in variable measure. As in its most serious forms, which are not infrequent, acne vulgaris may cause disfiguring scars, it is in fact a disease with large psychical implications that may result in social maladjustment and self-isolation.
Among the aetiological factors in the pathogenesis of acne vulgaris are an increase in the sebum production which is under influence of plasmatic androgens; an abnormal keratinization, with consequent accumulation of horny material at a follicle's level; a
predominance, in the bacterial flora of the skin, of micro-organisms belonging to the propionibacteria (P. acnes, P. avidum and P. granulosum) and to staphylococcus. By hydrolysis of sebum, these germs liberate Free Fatty Acids (FFA) , which are particularly irritant at skin level and are responsible for the initial inflammatory lesions typical of acne.
At present, there exists no single therapy for acne vulgaris. A variety of therapeutical agents available, but none of them performs a real healing action, neither from a symptomatology point of view, nor in a pathogenic sense, by removing the cause.
In practice, all these medicines present significant harmful collateral effects. They can be classified in two groups, depending on their utilisation in topical or systemic therapies.
The topical therapy is based on the use of compounds against seborrhoea compositions with keratolytic action (benzoyl peroxide) , with a basis of retinoic acid, estrogens and topical corticosteroids .
Topical preparations against seborrhoea in general are available in a huge variety of lotions, creams, powders containing sulphur, salicylic acid and resorcinol. The majority of these products are irritant when applied onto the skin, and the best results are obtained when they are used with they produce a non-
damaging exsiccation and an exfoliation of the affected skin. A too limited use offers a very limited advantage, while an excessive use may be the cause of further lesions and pain. All these products might induce further seborrhoea.
Benzoyl peroxide acts as an exfoliating and a keratolytic agent. Therapeutic results are not obtained before 5-6 weeks. This treatment may produce skin irritation at various degrees and eczema.
Retinoic acids acts against the creation of comedones. The greatest handicap of this product is its irritating action that, during the first month of treatment or even further, may cause a deterioration of the lesions, with erythema and desquamation, and such collateral effects might lead to a suspension of the therapy.
Topical therapies with estrogens or corticoids in particular used as anti-inflammatories, present the risk of superinfection.
As for the systemic therapy, the effectiveness of the treatment with chemotherapeutic agents and antibiotics is debatable, as there might occur photo- sensitization and modification of the bacterial flora.
The hormonic therapy has several drawbacks. First of all, male patients are excluded from the treatment; secondly, therapeutic effects are detectable only after
months; finally, the best results are obtained using preparations with a higher level of estrogens, which yet present the greatest risks of thrombosis and embolism. Usually the hormonic therapy is employed in young female patients with acne clearly becoming acute in pre-menstrual periods.
It is the aim of the present invention to solve above mentioned problems realizing a pharmaceutical composition for topical treatment.
The present invention derives from the discovery that tromethamine and its pharmacologically acceptable salts, such as acetate, carbonate, citrate, phosphate, succinate and sulfate, administered in topical applications, are extremely effective anti-acne agents, not presenting the considerable side effects of known medicines .
The aim set forth is reached, according to the present invention, by a pharmaceutical composition according to above scientific and experimental discovery, comprising tromethamine and/or its pharmacologically acceptable salts in preparations for topical use such as creams, emulsions, solutions, lotions, in spray containers and similar.
As it is known from the prior art, tromethamine and its pharmacologically acceptable salts have never
been formulated in preparations for topical use for therapeutic purposes.
Hereinbelow, examples of preparations for topical use, according to the present invention, are listed.
All compositions are given per 100 g of their formulation.
1. Spray composition: tromethamine gr. 3.60 citric acid " 0.65 cetyl-stearyl-ethoxylate alcohol " 2.00 water " 83.70 freon 12 - Freon 114 (15/85) " 10.00
2. Cream composition: tromethamine gr. 3.60 citric acid " 0.65 silicon oil " 0.15 soya lecithin " 1.00 sodium stearyl lactilate " 1.50 cetyl-stearyl-ethoxylate alcohol " 14.00 propylene glycol " 4.00 glycerin " 2.00 nipasept " 0.15 water " 73.00
3. Milk composition: tromethamine gr. 3.6 citric acid " 0.65
silicon oil " 0.15 soya lecithin " 1.00 sodium stearyl lactilate " 2.00 cetyl-stearyl-ethoxylate alcohol w 5.00 nipasept " 0.15 water " 87.40
0.3 - 0.9 molar of tromethamine with acetic acid 0.1 -
0.3 molar watery solutions may also be used.
The working of the composition according to the present invention has been tested, using a 3.6% tromethamine solution (thamesol of Baxter hydroxymethyl - aminomethane 0.3 M - Acetic acid 0.1
M) .
Male and female patients in the age range from 13 to 18 years have been treated with a 3.6% tromethamine solution.
The clinical varieties treated were mixed forms of acne microcystica-comedonica and papulo-pustulosa, with a wide range of seriousness and extension of skin lesions.
All patients had been treated before with known, ordinary products and methodologies with unsatisfactory results.
For what concerns the methodology, before each application an accurate cleansing of the affected areas
of the face is to be performed with water and neutral soap.
On the dry face, the medication is applied and the skin is gently rubbed with wads watered with abundant tromethamine solution on all the points concerned. As an alternative, and especially at the beginning of the treatment, the application for a few minutes of a pledget soaked with solution has proved to be effective; the skin may dry at ambient air.
Applications should be repeated three or four times a day, the first one in the morning, after waking up, the last before going to sleep.
Already after a few days of treatment, noticeable improvement of the subjective symptomatology and of the pathologic phenomenon has been pointed out. The skin shows a definitely less greasy appearance; its surface is smoother and more regular; its colour is clearer and more uniform.
In the cases of acne papulo-pustulosa, the regression of the inflammatory component is constant and fast; as for the pustular elements, those already present at the beginning of the treatment come to a halt and are then slowly resolved, while no new element appears.
Continuing the treatment, possibly with just two or three applications per day, the results further improve
with a total "restitutio ad integrum" of the dermal tissue.
Based on the above as well as on other clinical tests in which different pharmaceutical forms have been employed such as creams and emulsions, it can be concluded that tromethamine and its pharmacologically acceptable salts perform a progressive and constant therapeutical action in the topical treatment of acne vulgaris .
The first event is shown by a rapid halt to the evolution of cutaneous lesions, followed by a constant regression, up to the complete remission, of the objective symptomatology. Such an effect is most evident towards the inflammatory component.
The experimental results have suggested that, firstly, tromethamine seems to act prevailingly due to its buffer action towards an excess of H+ ions, freed by free fat acids, which are particularly irritant at the skin level. The following restoration of the physiological values of the pH of these structures would represent the fundamental premises for the normalisation of the cellular biological processes, together with those linked to phenomena of immunity defence reaction.
Secondly, the rectification of the abnormally lowered pH may determine the inhibition of those
enzymatic activities (in particular, phospholipases) with an optimum in acid media (pH 5-6) , which give rise to the liberation of free fat acids.
Thirdly, it seems likely that a certain role is played by tromethamine due to its surface-active features; such features beyond ensuring a deep penetration, also promote the emulsion phenomena of the cutaneous hydrolipidic system, thus favouring the dismissal of abnormal sebaceous secretions.
Finally the possible keratolytic actions should be mentioned which, in different measure, are a feature of all alkaline substances.
Claims
A pharmaceutical tromethamine composition for a topical treatment of acne vulgaris, for the realization of creams, milks, lotions and similar containing 1 to 10 grams of tromethamine for each
100 gr.
A composition according to claim 1, characterized in the presence of acetate, carbonate, citrate, phosphate, tromethamine succinate or sulfate.
A composition according to claim 1, characterized in the realization of a watery solution containing from 0.3 to 0.9 mole/litre of tromethamine or its pharmacologically acceptable salt.
A composition according to claim 1, characterized in the realization of a cream containing, per 100 grams of cream:
Tromethamine gr . 3 . 60
Citric acid 0 . 65
Silicon oil 0 . 15
Soya lecithin 1 00
Sodium stearyl lactilate 1 50
Cetyl-stearyl-ethoxylate alcohol 14 00
Propylene glycol 4 00
Glycerin 2 00
Nipasept 0 15
Water " 73 . 00
5. A composition according to claim 1, characterized in the realization of a milk containing, per 100 grams of milk:
Tromethamine gr. 3.6
Citric acid " 0.65
Silicon oil " 0.15
Soya lecithin " 1.00
Sodium stearyl lactilate " 2.00
Cetyl-stearyl-ethoxylate alcohol " 5.00
Nipasept " 0.15
Water " 87.40
6. A composition according to claim 1, characterized in the realization of a spray lotion containing, per 100 grams of lotion:
Tromethamine gr. 3.60
Citric acid " 0.65
Cetyl-stearyl-ethoxylate alcohol " 2.00
Water " 83.70
Freon 12 - Freon 114 (15/85) " 10.00
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITCA96A000022 | 1996-10-17 | ||
| ITCA960022 IT1288708B1 (en) | 1996-10-17 | 1996-10-17 | PHARMACEUTICAL COMPOSITION INCLUDING THOMETAMINE FOR THE TOPICAL TREATMENT OF ACNE VULGARIS. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1998017265A1 true WO1998017265A1 (en) | 1998-04-30 |
Family
ID=11347108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IT1997/000239 Ceased WO1998017265A1 (en) | 1996-10-17 | 1997-10-06 | Pharmaceutical composition containing tromethamine for the topical treatment of acne vulgaris |
Country Status (2)
| Country | Link |
|---|---|
| IT (1) | IT1288708B1 (en) |
| WO (1) | WO1998017265A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018177778A (en) * | 2017-04-10 | 2018-11-15 | 花王株式会社 | Skin cleanser composition |
| CN110494120A (en) * | 2017-04-10 | 2019-11-22 | 花王株式会社 | How to remove corner plugs |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994021271A1 (en) * | 1993-03-19 | 1994-09-29 | Cellegy Pharmaceuticals, Inc. | Methods and compositions for inducing phase separation of epithelial lipid bilayers |
| US5352389A (en) * | 1991-07-08 | 1994-10-04 | Crinos Industria Farmacobiologica Spa | Composition for the cleaning of the skin, scalp and hair |
| WO1995000176A1 (en) * | 1993-06-18 | 1995-01-05 | Allergan, Inc. | Compositions for treating hypoxia-associated ocular complications |
| WO1995033489A1 (en) * | 1994-06-07 | 1995-12-14 | Allergan | Stable gel formulation for topical treatment of skin conditions |
| WO1996014055A1 (en) * | 1994-11-04 | 1996-05-17 | The Procter & Gamble Company | Buffered emulsion compositions containing actives subject to acid or base hydrolysis |
-
1996
- 1996-10-17 IT ITCA960022 patent/IT1288708B1/en active IP Right Grant
-
1997
- 1997-10-06 WO PCT/IT1997/000239 patent/WO1998017265A1/en not_active Ceased
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5352389A (en) * | 1991-07-08 | 1994-10-04 | Crinos Industria Farmacobiologica Spa | Composition for the cleaning of the skin, scalp and hair |
| WO1994021271A1 (en) * | 1993-03-19 | 1994-09-29 | Cellegy Pharmaceuticals, Inc. | Methods and compositions for inducing phase separation of epithelial lipid bilayers |
| WO1995000176A1 (en) * | 1993-06-18 | 1995-01-05 | Allergan, Inc. | Compositions for treating hypoxia-associated ocular complications |
| WO1995033489A1 (en) * | 1994-06-07 | 1995-12-14 | Allergan | Stable gel formulation for topical treatment of skin conditions |
| WO1996014055A1 (en) * | 1994-11-04 | 1996-05-17 | The Procter & Gamble Company | Buffered emulsion compositions containing actives subject to acid or base hydrolysis |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018177778A (en) * | 2017-04-10 | 2018-11-15 | 花王株式会社 | Skin cleanser composition |
| CN110494120A (en) * | 2017-04-10 | 2019-11-22 | 花王株式会社 | How to remove corner plugs |
| EP3610848A4 (en) * | 2017-04-10 | 2021-01-06 | Kao Corporation | SKIN CLEANSING COMPOSITION |
| EP3610849A4 (en) * | 2017-04-10 | 2021-01-13 | Kao Corporation | PROCEDURE FOR REMOVING KERATIN PLUGS |
| US11406576B2 (en) | 2017-04-10 | 2022-08-09 | Kao Corporation | Method for removing keratotic plugs |
| US11975086B2 (en) | 2017-04-10 | 2024-05-07 | Kao Corporation | Method for removing keratotic plugs |
Also Published As
| Publication number | Publication date |
|---|---|
| IT1288708B1 (en) | 1998-09-23 |
| ITCA960022A1 (en) | 1998-04-17 |
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