CA2413923A1 - Treatment of inflammatory dermatoses comprising erythromycin or clarythromycin metronidazole and a gastrointestinal hydrogen pump inhibitor - Google Patents
Treatment of inflammatory dermatoses comprising erythromycin or clarythromycin metronidazole and a gastrointestinal hydrogen pump inhibitor Download PDFInfo
- Publication number
- CA2413923A1 CA2413923A1 CA002413923A CA2413923A CA2413923A1 CA 2413923 A1 CA2413923 A1 CA 2413923A1 CA 002413923 A CA002413923 A CA 002413923A CA 2413923 A CA2413923 A CA 2413923A CA 2413923 A1 CA2413923 A1 CA 2413923A1
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- Prior art keywords
- analogue
- derivative
- use according
- metronidazole
- erythromycin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
Abstract
Use of i) erythromycin, clarithromycin or an analogue or derivative thereof; ii) metronidazole or an analogue or derivative thereof; and iii) omeprazole or an analogue or derivative thereof, for the manufacture of a medicament for t he treatment of a condition selected from the group consisting of inflammatory dermatomes, and in particular papulopustular rosacea and similar inflammator y papulopustular dermatoses.
Description
TREATMENT OF INFLAMMATORY DERMATOSES COMPRISING ERYTHROMYCIN OR
CLARYTHROMYCIN, METRONIDAZOLE AND A GASTROINTESTINAL HYDROGEN PUMP INHIBITOR
Field of the Invention The present invention relates to the treatment of skin conditions such as rosacea and similar inflammatory dermatoses, and in particular to the treatment of certain kinds of rosacea, and also perioral papular and pustular acne, and other papulopustular dermatoses.
Background to the Invention Rosacea is a chronic inflammatory disease which affects the face. It is characterised by episodic flushing, erythema, and telangiectasia affecting the cheeks, chin, forehead, and nose. It may be further complicated by inflammatory swelling, papules and pustules.
It is observed more frequently in women than in men, with an age of onset between 30 and 50, most commonly in those of Celtic or northern European descent.
Current treatments of rosacea include long-term the use of systemic or topical antibiotics, such as tetracycline, minocycline, doxicycline, erythromycin and metronidazole. However, such treatments are ineffective in achieving eradication of the condition, even for relatively short periods of time.
Many theories have been proposed to explain the aetiology of rosacea, with a view to finding alternative treatments thereof. An association with gastrointestinal disease has been considered as long ago as 1920 when achlorhdria and hypochlorohydria were thought to be predisposing factors. However, attempts to confirm such an association have been unsuccessful. Hypersensitivity to Demodex folliculorum, a mite which inhabits the facial pilosebaceous follicle, has also been postulated to be of relevance, and increased numbers of Demodex mites have been demonstrated in rosacea.
The association between rosacea and gastrointestinal disease has been revisited since the discovery that the Gram-negative bacterium Helicobacter pylori (H.Pylori) is the cause of gastritis and duodenal ulcer disease. Based on case-series studies of rosacea, several authors have reported higher than expected H. pylori seroprevalance and antibody titres, and have commented on improvement in the dermatological condition following H. pylori eradication therapy; see Rebora et al, Dermatology (1995) 89:1603-1604, Kolibasora et al, Archives of Dermatology (1996) 132:1393, and Utas et al, J.AM.Acad. Dermatology (1999) 40:433-435.
Yet none of these studies employed proper controls for their results to be considered meaningful. Furthermore, a number of other studies have failed to confirm the alleged relationship between H.Pylori and rosacea; see Jones et a1, Archives of Dermatology (1998) 134:511, and Bamford et al, Archives of Dermatology (1999) 135:659-663.
The situation in this respect, therefore, remains conflicting and unclear, as does the cause of this common, yet poorly understood, facial dermatosis.
Summary of the Invention Surprisingly, and as a result of case-controlled studies, we have now found that rosacea and similar inflammatory skin dermatoses can be effectively treated by administering to a patient a treatment regime comprising i) erythromycin, clarithromycin or an analogue or derivative thereof, ii) metronidazole or an analogue or derivative thereof, and iii) a gastrointestinal hydrogen pump inhibitor, such as omeprazole or an analogue or derivative thereof. The three drugs may be formulated for simultaneous, separate or sequential use.
These studies have also lead us to believe that the different signs of rosacea expressed by patients may in fact have different causes, and may not be linked to one another. For some time, it has beers believed that the different signs of rosacea are merely symptomatic of different, progressive, stages of the same general condition. Specifically, it has been suggested that the seemingly lesser signs of inflammatory rosacea (erythema and telangiectasis) progress to lesions and/or papulopustular signs (pimples on the skin). We believe that this may not be true, as patients have been observed to exhibit either inflammatory signs or papulopustular signs. Instead, the different signs may represent distinct types of rosacea.
While the triple drug combination described above is useful in treating rosacea as a generality, we have discovered that it is particularly useful in the treatment of papulopustular rosacea, perioral dermatitis (perioral rosacea), and perioral pustular or papular acne.
At present, it is not understood how the triple drug combination according to the present invention functions in achieving the desired results. One possibility is that there may be a causal relationship between the dermatoses to be treated and H.pylori, such that eradication of H.pylori may lead to resolution of these dermatoses.
Another possibility is that as, in certain instances, the presence of H.pylori has been found in pustules on the skin, the triple drug combination may act directly to eradicate that external form of H.pylori. Yet another possibility is that the triple drug combination works in another manner, such that any apparent relationship between its use in the present invention and H.pylori may simply be coincidental, such that further study will be necessary elucidate its precise mode of action.
Description of the Invention The preferred treatment regime comprises erythromycin or clarithromycin, metronidazole and omeprazole, and the most preferred treatment regime comprises clarithromycin, metronidazole and omeprazole. As mentioned above, however analogues or derivatives of any of these drugs may be used provided that their combined administration achieves the desired result. For instance, another similar-acting macrolide antibiotic to erythromycin or clarithromycin may be used, for instance azithromycin or dirithromycin.
Similarly, lanzoprazole or any other drug which acts to inhibits a gastrointestinal hydrogen pump, may be used instead of omeprazole. Additionally, other drugs may be useful which have a similar or equivalent pharmacological mode of action to the drugs named above. Pharmaceutically-acceptable salt forms of the drugs may also be used.
Treatment may be by administration of the three drugs by any suitable means. Conveniently, however, the three drugs will be administered by one or a combination of oral administration, topical application to a patient's skin, or parenteral administration, e.g. intravenous, intramuscular or subcutaneous administration. For instance, one or more of the three drugs may be formulated for administration by a different route to the other drug(s). Typically, it is desirable to administer omeprazole or an analogue thereof orally, but the other drugs may be formulated for oral, topical or parenteral administration, or any combination thereof. For instance, it may be preferred to administer omeprazole orally and the other two drugs topically, optionally as a combined topical formulation.
If the triple drug combination is to be administered orally, it may take the form of separate pills containing each of the separate drugs, for simultaneous, separate or sequential administration. Preferably, however, the three drugs will be combined into a single dosage form, preferably a tablet, capsule or linctus, for patient convenience. In the case of topical or parenteral administration, the drugs are incorporated into a suitable pharmaceutically-acceptable carrier. Such formulations have not been disclosed in the prior art, and constitute further aspects of the claimed invention.
The relative proportions of the three drugs necessary for effective treatment may vary depending on the route of administration, and the particular patient to be treated.
Typically, however, a patient will receive 200 to 600 mg, preferably 300 to 500 mg of erythromycin, clarithromycin or an analogue thereof, 200 to 500 mg, preferably 300 to 500 mg, metronidazole, and 10 to 100 mg, preferably 20 to 60 mg, omeprazole, on a daily basis. A particularly preferred treatment regime, however, comprises about 250 mg erythromycin, clarithromycin or an analogue thereof, about 400 mg metronidazole and about 20 mg omeprazole. Treatment periods vary from patient to patient, from one week to a 5 number of years.
The results upon which the present invention are based are summarised in the following example.
Example 42 patients with rosacea and evidence of infection with H.pylori were studied. At week 0, an initial assessment of the severity of each of the patient's skin disease was made, using the so-called "Coventry Scoring System"; see Br. J. Derm. (1995) 133, Suppl. 45, 34. This scoring system, developed in the Dermatology Department at Walsgrave Hospital, Coventry, UK, measures the severity of rosacea in five different facial areas and for six different parameters. The different facial areas are depicted in Figure 1, below. The different parameters are erythema, telangiectasia, papules, pustules, oedema and scaling. For each parameter in each area, a score of one is given if less than half the area involved is affected by that parameter, and a score of two if half or more of the area is affected. The scores for the different parameters in the different facial areas are added together to give a total score for the patient.
Each patient was subjected to clinical photography, and then treated with an oral dosage of 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin for one week. Disease severity scoring and clinical photography were repeated at the end of weeks 6, 12, 18, and 24, and fourteen patients were followed for a period of 52 weeks.
At week 0 the mean severity score was 10 (range 3-24) .
Following treatment, at week 6 the mean score had fallen to 5.8 (range 2-12) , falling further to 4.6 (range 2-8) at week 12. At weeks 18 and 24 the mean severity scores were 4.5 (range 2-12) and 5.6 (range 2-14) respectively. There was a significant difference between scores at week 0 and weeks 6 and 12 (p<0.0001), and also between scores at week 0 and weeks 18, and 24 (p<0.001). Five relapses were recorded, one at week 18 and four at week 24, with rosacea severity scores returning to values seen at week 0.
The study demonstrates that the combined treatment of omeprazole, metronidazole and clarithromycin was effective in the treatment of symptoms associated with rosacea in general. It was noted in particular that the treatment significantly reduced papules and/or pustules on patients' faces .
While the study treated patients with evidence of infection with H.pylori, because a causal relationship between successful treatment of rosacea and eradication of H.pylori is yet to be confirmed, it is believed that the triple drug combination of the present invention may be useful in the treatment of patients who are not infected with H.pylori.
CLARYTHROMYCIN, METRONIDAZOLE AND A GASTROINTESTINAL HYDROGEN PUMP INHIBITOR
Field of the Invention The present invention relates to the treatment of skin conditions such as rosacea and similar inflammatory dermatoses, and in particular to the treatment of certain kinds of rosacea, and also perioral papular and pustular acne, and other papulopustular dermatoses.
Background to the Invention Rosacea is a chronic inflammatory disease which affects the face. It is characterised by episodic flushing, erythema, and telangiectasia affecting the cheeks, chin, forehead, and nose. It may be further complicated by inflammatory swelling, papules and pustules.
It is observed more frequently in women than in men, with an age of onset between 30 and 50, most commonly in those of Celtic or northern European descent.
Current treatments of rosacea include long-term the use of systemic or topical antibiotics, such as tetracycline, minocycline, doxicycline, erythromycin and metronidazole. However, such treatments are ineffective in achieving eradication of the condition, even for relatively short periods of time.
Many theories have been proposed to explain the aetiology of rosacea, with a view to finding alternative treatments thereof. An association with gastrointestinal disease has been considered as long ago as 1920 when achlorhdria and hypochlorohydria were thought to be predisposing factors. However, attempts to confirm such an association have been unsuccessful. Hypersensitivity to Demodex folliculorum, a mite which inhabits the facial pilosebaceous follicle, has also been postulated to be of relevance, and increased numbers of Demodex mites have been demonstrated in rosacea.
The association between rosacea and gastrointestinal disease has been revisited since the discovery that the Gram-negative bacterium Helicobacter pylori (H.Pylori) is the cause of gastritis and duodenal ulcer disease. Based on case-series studies of rosacea, several authors have reported higher than expected H. pylori seroprevalance and antibody titres, and have commented on improvement in the dermatological condition following H. pylori eradication therapy; see Rebora et al, Dermatology (1995) 89:1603-1604, Kolibasora et al, Archives of Dermatology (1996) 132:1393, and Utas et al, J.AM.Acad. Dermatology (1999) 40:433-435.
Yet none of these studies employed proper controls for their results to be considered meaningful. Furthermore, a number of other studies have failed to confirm the alleged relationship between H.Pylori and rosacea; see Jones et a1, Archives of Dermatology (1998) 134:511, and Bamford et al, Archives of Dermatology (1999) 135:659-663.
The situation in this respect, therefore, remains conflicting and unclear, as does the cause of this common, yet poorly understood, facial dermatosis.
Summary of the Invention Surprisingly, and as a result of case-controlled studies, we have now found that rosacea and similar inflammatory skin dermatoses can be effectively treated by administering to a patient a treatment regime comprising i) erythromycin, clarithromycin or an analogue or derivative thereof, ii) metronidazole or an analogue or derivative thereof, and iii) a gastrointestinal hydrogen pump inhibitor, such as omeprazole or an analogue or derivative thereof. The three drugs may be formulated for simultaneous, separate or sequential use.
These studies have also lead us to believe that the different signs of rosacea expressed by patients may in fact have different causes, and may not be linked to one another. For some time, it has beers believed that the different signs of rosacea are merely symptomatic of different, progressive, stages of the same general condition. Specifically, it has been suggested that the seemingly lesser signs of inflammatory rosacea (erythema and telangiectasis) progress to lesions and/or papulopustular signs (pimples on the skin). We believe that this may not be true, as patients have been observed to exhibit either inflammatory signs or papulopustular signs. Instead, the different signs may represent distinct types of rosacea.
While the triple drug combination described above is useful in treating rosacea as a generality, we have discovered that it is particularly useful in the treatment of papulopustular rosacea, perioral dermatitis (perioral rosacea), and perioral pustular or papular acne.
At present, it is not understood how the triple drug combination according to the present invention functions in achieving the desired results. One possibility is that there may be a causal relationship between the dermatoses to be treated and H.pylori, such that eradication of H.pylori may lead to resolution of these dermatoses.
Another possibility is that as, in certain instances, the presence of H.pylori has been found in pustules on the skin, the triple drug combination may act directly to eradicate that external form of H.pylori. Yet another possibility is that the triple drug combination works in another manner, such that any apparent relationship between its use in the present invention and H.pylori may simply be coincidental, such that further study will be necessary elucidate its precise mode of action.
Description of the Invention The preferred treatment regime comprises erythromycin or clarithromycin, metronidazole and omeprazole, and the most preferred treatment regime comprises clarithromycin, metronidazole and omeprazole. As mentioned above, however analogues or derivatives of any of these drugs may be used provided that their combined administration achieves the desired result. For instance, another similar-acting macrolide antibiotic to erythromycin or clarithromycin may be used, for instance azithromycin or dirithromycin.
Similarly, lanzoprazole or any other drug which acts to inhibits a gastrointestinal hydrogen pump, may be used instead of omeprazole. Additionally, other drugs may be useful which have a similar or equivalent pharmacological mode of action to the drugs named above. Pharmaceutically-acceptable salt forms of the drugs may also be used.
Treatment may be by administration of the three drugs by any suitable means. Conveniently, however, the three drugs will be administered by one or a combination of oral administration, topical application to a patient's skin, or parenteral administration, e.g. intravenous, intramuscular or subcutaneous administration. For instance, one or more of the three drugs may be formulated for administration by a different route to the other drug(s). Typically, it is desirable to administer omeprazole or an analogue thereof orally, but the other drugs may be formulated for oral, topical or parenteral administration, or any combination thereof. For instance, it may be preferred to administer omeprazole orally and the other two drugs topically, optionally as a combined topical formulation.
If the triple drug combination is to be administered orally, it may take the form of separate pills containing each of the separate drugs, for simultaneous, separate or sequential administration. Preferably, however, the three drugs will be combined into a single dosage form, preferably a tablet, capsule or linctus, for patient convenience. In the case of topical or parenteral administration, the drugs are incorporated into a suitable pharmaceutically-acceptable carrier. Such formulations have not been disclosed in the prior art, and constitute further aspects of the claimed invention.
The relative proportions of the three drugs necessary for effective treatment may vary depending on the route of administration, and the particular patient to be treated.
Typically, however, a patient will receive 200 to 600 mg, preferably 300 to 500 mg of erythromycin, clarithromycin or an analogue thereof, 200 to 500 mg, preferably 300 to 500 mg, metronidazole, and 10 to 100 mg, preferably 20 to 60 mg, omeprazole, on a daily basis. A particularly preferred treatment regime, however, comprises about 250 mg erythromycin, clarithromycin or an analogue thereof, about 400 mg metronidazole and about 20 mg omeprazole. Treatment periods vary from patient to patient, from one week to a 5 number of years.
The results upon which the present invention are based are summarised in the following example.
Example 42 patients with rosacea and evidence of infection with H.pylori were studied. At week 0, an initial assessment of the severity of each of the patient's skin disease was made, using the so-called "Coventry Scoring System"; see Br. J. Derm. (1995) 133, Suppl. 45, 34. This scoring system, developed in the Dermatology Department at Walsgrave Hospital, Coventry, UK, measures the severity of rosacea in five different facial areas and for six different parameters. The different facial areas are depicted in Figure 1, below. The different parameters are erythema, telangiectasia, papules, pustules, oedema and scaling. For each parameter in each area, a score of one is given if less than half the area involved is affected by that parameter, and a score of two if half or more of the area is affected. The scores for the different parameters in the different facial areas are added together to give a total score for the patient.
Each patient was subjected to clinical photography, and then treated with an oral dosage of 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin for one week. Disease severity scoring and clinical photography were repeated at the end of weeks 6, 12, 18, and 24, and fourteen patients were followed for a period of 52 weeks.
At week 0 the mean severity score was 10 (range 3-24) .
Following treatment, at week 6 the mean score had fallen to 5.8 (range 2-12) , falling further to 4.6 (range 2-8) at week 12. At weeks 18 and 24 the mean severity scores were 4.5 (range 2-12) and 5.6 (range 2-14) respectively. There was a significant difference between scores at week 0 and weeks 6 and 12 (p<0.0001), and also between scores at week 0 and weeks 18, and 24 (p<0.001). Five relapses were recorded, one at week 18 and four at week 24, with rosacea severity scores returning to values seen at week 0.
The study demonstrates that the combined treatment of omeprazole, metronidazole and clarithromycin was effective in the treatment of symptoms associated with rosacea in general. It was noted in particular that the treatment significantly reduced papules and/or pustules on patients' faces .
While the study treated patients with evidence of infection with H.pylori, because a causal relationship between successful treatment of rosacea and eradication of H.pylori is yet to be confirmed, it is believed that the triple drug combination of the present invention may be useful in the treatment of patients who are not infected with H.pylori.
Claims (17)
1. Use of i) erythromycin, clarythromycin or an analogue or derivative thereof;
ii) metronidazole; or an analogue or derivative thereof; and iii) a gastrointestinal hydrogen pump inhibitor, for the manufacture of a medicament for the treatment of a condition selected from the group consisting of inflammatory dermatoses.
ii) metronidazole; or an analogue or derivative thereof; and iii) a gastrointestinal hydrogen pump inhibitor, for the manufacture of a medicament for the treatment of a condition selected from the group consisting of inflammatory dermatoses.
2. Use according to claim 1, wherein the condition is rosacea.
3. Use according to claim 1, wherein the condition is an inflammatory papular or pustular dermatitis.
4. Use according to claim 3, wherein the condition is papulopustular rosacea.
5. Use according to claim 1, wherein the condition is perioral dermatitis.
6. Use according to claim 1, wherein the condition is perioral papular or pustular acne.
7. Use according to any preceding claim, wherein the gastrointestinal hydrogen pump inhibitor is omeprazole or an analogue or derivative thereof.
8. Use according to any preceding claim, wherein the medicament is for oral administration.
9. Use according to any of claims 1 to 8, wherein the medicament is for topical administration.
10. Use according to any of claims 1 to 8, wherein the medicament is for parenteral administration.
11. Use according to any of claims 1 to 3, wherein components (i) to (iii) are formulated for a combination of oral administration, topical administration and/or parenteral administration.
12. Use according to claim 11, wherein component (ii) is formulated for oral administration and components (i) and (iii) are formulated for topical administration.
13. A dosage form comprising, in a single unit, a combination of i) erythromycin, clarithromycin or an analogue or derivative thereof;
ii) metronidazole or an analogue or derivative thereof; and iii) a gastrointestinal hydrogen pump inhibitor.
ii) metronidazole or an analogue or derivative thereof; and iii) a gastrointestinal hydrogen pump inhibitor.
14. A dosage form according to claim 13, wherein the gastrointestinal hydrogen pump inhibitor is omeprazole or an analogue or derivative thereof.
15. A dosage form according to claim 13 or claim 14, which is a tablet or capsule.
16. A topical pharmaceutical composition comprising, in a pharmaceutically-acceptable carrier, one or a combination of i) erythromycin, clarithromycin or an analogue or derivative thereof;
ii) metronidazole or an analogue or derivative thereof; and iii) a gastrointestinal hydrogen pump inhibitor, such as omeprazole or an analogue or derivative thereof.
ii) metronidazole or an analogue or derivative thereof; and iii) a gastrointestinal hydrogen pump inhibitor, such as omeprazole or an analogue or derivative thereof.
17. A parenteral pharmaceutical composition comprising, in a pharmaceutically-acceptable carrier suitable for parenteral administration, one or a combination of i) erythromycin, clarithromycin or an analogue or derivative thereof;
ii) metronidazole or an analogue or derivative thereof; and iii) a gastrointestinal hydrogen pump inhibitor, such as omeprazole or an analogue or derivative thereof.
ii) metronidazole or an analogue or derivative thereof; and iii) a gastrointestinal hydrogen pump inhibitor, such as omeprazole or an analogue or derivative thereof.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00301951.0 | 2000-03-09 | ||
EP00301951A EP1133987A1 (en) | 2000-03-09 | 2000-03-09 | Treatment of inflammatory dermatoses with combinations of erythromycin or clarythromycin, metronidazole and a hydrogen pump inhibitor |
US18896100P | 2000-03-10 | 2000-03-10 | |
US60/188,961 | 2000-03-10 | ||
PCT/GB2001/001047 WO2001066117A1 (en) | 2000-03-09 | 2001-03-09 | Treatment of inflammatory dermatoses comprising erythromycin or clarythromycin metronidazole and a gastrointestinal hydrogen pump inhibitor |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2413923A1 true CA2413923A1 (en) | 2001-09-13 |
Family
ID=26073033
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002413923A Abandoned CA2413923A1 (en) | 2000-03-09 | 2001-03-09 | Treatment of inflammatory dermatoses comprising erythromycin or clarythromycin metronidazole and a gastrointestinal hydrogen pump inhibitor |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1263445A1 (en) |
AU (1) | AU3762801A (en) |
CA (1) | CA2413923A1 (en) |
WO (1) | WO2001066117A1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003049716A1 (en) * | 2001-12-13 | 2003-06-19 | Ranbaxy Laboratories Limited | Stable topical formulation of clarithromycin |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2591105B1 (en) * | 1985-12-11 | 1989-03-24 | Moet Hennessy Rech | PHARMACEUTICAL COMPOSITION, IN PARTICULAR DERMATOLOGICAL, OR COSMETIC, BASED ON HYDRATED LIPID LAMELLAR PHASES OR LIPOSOMES CONTAINING A RETINOIDE OR A STRUCTURAL ANALOG OF SUCH A RETINOID AS A CAROTENOID. |
IS3990A (en) * | 1992-04-24 | 1993-10-25 | Ab Astra | Method of mixing substances that inhibit gastric acid and bacterial degrading agent in an acidic environment |
WO1995018612A1 (en) * | 1994-01-05 | 1995-07-13 | Aktiebolaget Astra | A method for treatment of psoriasis, by omeprazole or related compounds |
WO1996001622A1 (en) * | 1994-07-08 | 1996-01-25 | Astra Aktiebolag | New oral pharmaceutical formulation containing magnesium salt of omeprazole |
SE9500422D0 (en) * | 1995-02-06 | 1995-02-06 | Astra Ab | New oral pharmaceutical dosage forms |
JPH10158172A (en) * | 1996-11-29 | 1998-06-16 | Takeshi Azuma | Therapeutic agent for hepatic encephalopathy or preventing agent for hepatic encephalopathy |
US6017950A (en) * | 1997-08-05 | 2000-01-25 | Millennium Pharmaceuticals, Inc. | Methods for controlling gram negative bacteria in mammals |
GB9723669D0 (en) * | 1997-11-07 | 1998-01-07 | Univ Aberdeen | Skin penetration enhancing components |
-
2001
- 2001-03-09 WO PCT/GB2001/001047 patent/WO2001066117A1/en not_active Application Discontinuation
- 2001-03-09 CA CA002413923A patent/CA2413923A1/en not_active Abandoned
- 2001-03-09 AU AU37628/01A patent/AU3762801A/en not_active Abandoned
- 2001-03-09 EP EP01910045A patent/EP1263445A1/en not_active Withdrawn
Also Published As
Publication number | Publication date |
---|---|
WO2001066117A1 (en) | 2001-09-13 |
AU3762801A (en) | 2001-09-17 |
EP1263445A1 (en) | 2002-12-11 |
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