US20070225262A2 - Method for the treatment of acne - Google Patents
Method for the treatment of acne Download PDFInfo
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- US20070225262A2 US20070225262A2 US11/166,817 US16681705A US2007225262A2 US 20070225262 A2 US20070225262 A2 US 20070225262A2 US 16681705 A US16681705 A US 16681705A US 2007225262 A2 US2007225262 A2 US 2007225262A2
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- tetracycline antibiotic
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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
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
Definitions
- This invention relates to the treatment of acne vulgaris, commonly known simply as “acne.”
- Acne is a disease of the skin in which the pilosebaceous structures of the skin become inflamed, leading to the formation of comedones, pustules and nodules. Acne can lead to permanent scarring in severe cases.
- acne arises when hyperkeratosis of the pilosebaceous structure wholly or partially blocks the opening of the structure, resulting in comedones filled with sebum, keratin, and Propionibacterium acnes . These lesions are commonly identified as acne. P. acnes naturally occurs in normal skin, but is especially and characteristically present in acne lesions. It is believed that metabolic byproducts and waste from P. acnes within the pilosebaceous structures cause or contribute to the inflammation of acne lesions.
- Topical keratolytic agents such as salicylic acid are sometimes used. Keratolytic agents are thought to encourage the opening up of blocked pilosebaceous structures, thereby reducing conditions that are favorable to inflammation. Benzoyl peroxide, an anti-microbial, remains a popular and effective treatment. Topical antibiotics, such as clindamycin, which are effective against P. acnes , have also been used with a view towards preventing the formation of metabolic byproducts from this organism. Topical retinoids such as tretinoin have also been used in the treatment of acne.
- Systemic (i.e. non-topical) treatments for acne include the use of oral antibiotics in more serious cases. These treatments are directed towards the reduction in the amount P. acnes in the skin, especially the pilosebaceous structures, and seek to reduce the inflammation caused by waste materials and metabolic byproducts from these organisms. Tetracycline antibiotics are most commonly used for this purpose. These include tetracycline, minocycline and doxycycline. Erythromycin is also sometimes used.
- Standard oral minocycline therapy for acne in pediatric patients calls for the administration of a 4 mg/kg initial loading dose, and a 2 mg/kg dose every 12 hours thereafter. This results in a dose of 6 mg/kg on the first day of treatment and a 4 mg/kg dose each day thereafter. In adults, a 200 mg initial dose is followed by a 100 mg dose every 12 hours thereafter. In a typical patient, this results in about a 4.5 mg/kg dose on the first day of treatment, and 3.0 mg/kg dose each day thereafter.
- isotretinoin is sometimes used. While effective, isotretinoin is also powerfully teratogenic, and women of childbearing age are required to use multiple methods of contraception while taking the drug.
- a method for the treatment of acne in which an antibiotically effective dose of an oral tetracycline, such as minocycline, is provided.
- This dose is approximately 1 milligram per kilogram of body weight (1 mg/kg), without an initial loading dose of antibiotic.
- This antibiotic dosing regimen has been found to be as effective as a conventional dosing regimen incorporating a significant initial loading dose and higher subsequent doses.
- the dosing method of the current invention produces far fewer side effects.
- the oral tetracycline is provided in a dosage form that provides for the continued release of the antibiotic between doses, as opposed to an immediate or nearly immediate release of the drag.
- acne vulgaris is treated by the use of an oral tetracycline antibiotic, preferably minocycline.
- This antibiotic is administered in an antibiotically effective amount of approximately 1.0 milligram per kilogram of body weight per day (1.0 mg/kg/day). While this may be accomplished by the use of divided doses, it is preferred that the tetracycline antibiotic be delivered in a single daily dose.
- This treatment regime is initiated without a loading dose, and is continued until resolution or substantial resolution of the patient's acne.
- the course of treatment typically lasts 12 to up to 60 weeks, but will be adjusted according to the disease status and other medical conditions of each patient in the exercise of ordinary good clinical judgment by the patient's health care provider.
- delayed release dosage forms are known in the art, the formulation of them is far from predictable and the selection of a specific delayed release formulation is accomplished more by trial and error than by mathematical prediction based on known properties of delay release agents. No delayed release product useful in the present invention has been known heretofore.
- the ratio of fast dissolving carriers to slow dissolving carriers in the core caplet is important in obtaining a dissolution profile that enables once-a-day dosing in accordance with the present invention. By keeping the ratio of these components within a certain range, one may obtain this result.
- the fast dissolving carrier is any binder, vehicle, or excipient that quickly dissolves in an aqueous physiological medium, such as gastric fluid, thereby tending to quickly release the active ingredient. Lactose, its salts and hydrates are good examples of such components. It has been observed that sometimes a portion of the fast dissolving components are formulated in a manner that results in the complete or partial encapsulation or inclusion or coating of these fast-dissolving materials in granules of slow-dissolving materials. These encapsulated materials are excluded from the calculation of the above mentioned ratio of fast-dissolving to slow dissolving components.
- a slow dissolving carrier is any binder, vehicle, or excipient that dissolves slowly over the course of hours and perhaps a day, thereby slowing the release of the active ingredient.
- examples of such components are polyvinyl pyrrolidone, polyvinyl acetate, microcrystalline cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, or waxy or lipid-based tableting agents such as magnesium stearate or calcium stearate.
- Outer “enteric” coatings are excluded from this amount when calculating the above-mentioned ratio.
- Insoluble carriers are binders, vehicles, or excipients that are practically insoluble in physiological fluids, such as gastric fluid, and includes compounds, such as silicon dioxide and talc.
- Dosage forms such as capsules, tablets, and caplets that release 25 to 52% of the antibiotics within 1 hour, 53 to 89% in 2 hours, and at least 90% within 4 hours are suited to the once-a-day dosage regimen contemplated by the current inventories. More preferably, 30 to 52% of the antibiotic is released within 1 hour, 53 to 84% within 2 hours, and at least 85% within 4 hours.
- the oral tetracycline antibiotic may be delivered in a dosage form that releases the antibiotic in such a way that the maximum blood concentration of the antibiotic (C max ) is reached at about 3.5 hours after administration (T max ).
- the C max should be reached between 2.75 and 4.0 after administration, more preferably between 3.0 and 3.75 after administration.
- Quantity Component 135 mg Caplet Minocycline (as 145.8 hydrochloride) (dry weight) Lactose 107.4 Monohydrate (intragranular) Lactose 43.8 Monohydrate (extragranular) Total Lactose 151.2 Monohydrate HPMC 94 Silicon Dioxide 3 Mg. Stearate 6 45 mg Caplet Minocycline (as 48.6 hydrochloride) (dry weight) Lactose 192.2 Monohydrate (intragranular) Lactose 42.2 Monohydrate (extragranular) Total Lactose 234.40 Monohydrate HPMC 108 Silicon Dioxide 3 Mg. Stearate 6
- Each of these components is combined in a conventional fashion, compressed in a tabletting apparatus, and then provided in a conventional manner with a suitable coating, such as, without limitation Opadry II and optional coloring.
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Abstract
Description
- This invention relates to the treatment of acne vulgaris, commonly known simply as “acne.” Acne is a disease of the skin in which the pilosebaceous structures of the skin become inflamed, leading to the formation of comedones, pustules and nodules. Acne can lead to permanent scarring in severe cases.
- It is generally believed that acne arises when hyperkeratosis of the pilosebaceous structure wholly or partially blocks the opening of the structure, resulting in comedones filled with sebum, keratin, and Propionibacterium acnes. These lesions are commonly identified as acne. P. acnes naturally occurs in normal skin, but is especially and characteristically present in acne lesions. It is believed that metabolic byproducts and waste from P. acnes within the pilosebaceous structures cause or contribute to the inflammation of acne lesions.
- Conventional acne treatments have taken many forms. Topical keratolytic agents, such as salicylic acid are sometimes used. Keratolytic agents are thought to encourage the opening up of blocked pilosebaceous structures, thereby reducing conditions that are favorable to inflammation. Benzoyl peroxide, an anti-microbial, remains a popular and effective treatment. Topical antibiotics, such as clindamycin, which are effective against P. acnes, have also been used with a view towards preventing the formation of metabolic byproducts from this organism. Topical retinoids such as tretinoin have also been used in the treatment of acne.
- Systemic (i.e. non-topical) treatments for acne include the use of oral antibiotics in more serious cases. These treatments are directed towards the reduction in the amount P. acnes in the skin, especially the pilosebaceous structures, and seek to reduce the inflammation caused by waste materials and metabolic byproducts from these organisms. Tetracycline antibiotics are most commonly used for this purpose. These include tetracycline, minocycline and doxycycline. Erythromycin is also sometimes used.
- Standard oral minocycline therapy for acne in pediatric patients calls for the administration of a 4 mg/kg initial loading dose, and a 2 mg/kg dose every 12 hours thereafter. This results in a dose of 6 mg/kg on the first day of treatment and a 4 mg/kg dose each day thereafter. In adults, a 200 mg initial dose is followed by a 100 mg dose every 12 hours thereafter. In a typical patient, this results in about a 4.5 mg/kg dose on the first day of treatment, and 3.0 mg/kg dose each day thereafter.
- In cases where acne does not respond to oral antibiotic treatment, oral isotretinoin is sometimes used. While effective, isotretinoin is also powerfully teratogenic, and women of childbearing age are required to use multiple methods of contraception while taking the drug.
- While oral tetracycline antibiotics remain a highly favored and widely used treatment for more serious cases of acne, it is not without side effects. Vestibular side effects, including extreme dizziness and concomitant nausea, can be so severe as to result in discontinuance of tetracycline therapy. Long term use can sometimes result in vaginal candidisis, esophageal erosions and in antibiotic resistant infections.
- Some recent research has indicated that very low doses of oral tetracycline can result in some improvement of acne even though the dose of tetracycline is too low to have an antibiotic effect. This observation has been attributed to an anti-inflammatory effect of tetracycline compounds. This effect has been reported to have been observed even where a chemically modified tetracycline that have no antibiotic properties are used. The use of tetracycline antibiotics at a dose too low to have an antibiotic effect or the use of modified tetracycline having no antibiotic properties as treatments for acne has never been approved by any drug regulatory agency.
- According to the present invention, a method is provided for the treatment of acne in which an antibiotically effective dose of an oral tetracycline, such as minocycline, is provided. This dose is approximately 1 milligram per kilogram of body weight (1 mg/kg), without an initial loading dose of antibiotic. This antibiotic dosing regimen has been found to be as effective as a conventional dosing regimen incorporating a significant initial loading dose and higher subsequent doses. However, the dosing method of the current invention produces far fewer side effects.
- In another aspect of this invention, the oral tetracycline is provided in a dosage form that provides for the continued release of the antibiotic between doses, as opposed to an immediate or nearly immediate release of the drag.
- According to the present invention, acne vulgaris is treated by the use of an oral tetracycline antibiotic, preferably minocycline. This antibiotic is administered in an antibiotically effective amount of approximately 1.0 milligram per kilogram of body weight per day (1.0 mg/kg/day). While this may be accomplished by the use of divided doses, it is preferred that the tetracycline antibiotic be delivered in a single daily dose. This treatment regime is initiated without a loading dose, and is continued until resolution or substantial resolution of the patient's acne. The course of treatment typically lasts 12 to up to 60 weeks, but will be adjusted according to the disease status and other medical conditions of each patient in the exercise of ordinary good clinical judgment by the patient's health care provider.
- Controlled, double-blinded studies were undertaken to determine the effectiveness of this invention. Treatment of 473 patients with acne was undertaken according to the present invention. Placebos were provided to 239 patients. The effectiveness of the invention in treating acne vulgaris is shown in Table 1.
TABLE 1 Total Lesion Counts Total Lesions (as zebra Total Lesions Percent of Baseline) Baseline (mean) 169.3 100 Day 28 (mean) 134.0 78 Day 56 (mean) 119.3 69 Day 84 (mean) 112.3 66 Inflammatory Lesion Counts Inflammatory Lesions (as zebra Inflammatory Lesions Percent of Baseline) Baseline (mean) 77.4 100 Day 28 (mean) 52.1 66 Day 56 (mean) 44.3 56 Day 84 (mean) 41.9 53 - While effective as a treatment for acne, this resulted in almost no side effects above those observed with a placebo, as shown in Table 2.
TABLE 2 % Subjects with Adverse Events Minocycline Placebo At least One Adverse Event 56.2 54.1 At Least One Serious 0.4 0 Adverse Event Blood/Lymphatic System 0.3 0.3 Disorders Cardiac Disorders 0.3 0 Ear and Labyrinth Disorders 3.6 3.3 Endocrine Disorders 0.3 0 Eye Disorders 2.2 2.7 Gastrointestinal Disorders 21.2 26.1 General Disorders and 13.8 10.4 Administrative Site Conditions Immune System Disorders 0.7 2.5 Infections and Infestations 9.3 11.0 Laboratory Blood 0.7 1.1 Abnormalities Metabolism and Nutrition 0.6 0.3 Disorders Musculoskeletal and 4.6 3.6 Connective Disorders Neoplasms Benign, 0.1 0 Malignant and Unspecified Nervous System Disorders 29.2 25.8 Psychiatric Disorders 6.4 7.1 Renal and Urinary Disorders 0.3 0.5 Reproductive System and 0.7 0.3 Breast Disorders Respiratory, Thoracic and 5.3 6.9 Mediastinal Disorders Skin and Subcutaneous 8.6 7.1 Tissue Disorders Vascular Disorders 1.0 0.3 - The effectiveness of this invention can be seen by comparing the above efficacy data with published data on the effectiveness of conventional tetracycline treatments for acne in the reduction of total acne lesions and in the reduction of inflammatory lesions. See, e.g. Hersel & Gisslen, “Minocycline in Acne Vulgaris: A Double Blind Study,” Current Therapeutic Research, 1976.
- Because of the variations in body weight encountered in clinical practice, in the actual practice of this invention it is not practical to provide every patient with exactly 1 mg/kg/day of oral tetracycline antibiotic. However, it is acceptable to approximate this dose by providing the patient with from 0.5 to 1.5 mg/kg/day although from 0.7 to 1.3 mg/kg/day is preferred, and 1.0 mg/kg/day is ideal.
- While it can be effective to provide the oral tetracycline antibiotic in divided doses taken over the course of a day (e.g. twice or three times a day), it is preferable to provide the oral tetracycline antibiotic in a dosage form that releases the antibiotic slowly during the course of a day so that once-a-day dosing is possible. While delayed release dosage forms are known in the art, the formulation of them is far from predictable and the selection of a specific delayed release formulation is accomplished more by trial and error than by mathematical prediction based on known properties of delay release agents. No delayed release product useful in the present invention has been known heretofore.
- It has been discovered that the ratio of fast dissolving carriers to slow dissolving carriers in the core caplet is important in obtaining a dissolution profile that enables once-a-day dosing in accordance with the present invention. By keeping the ratio of these components within a certain range, one may obtain this result.
- The fast dissolving carrier is any binder, vehicle, or excipient that quickly dissolves in an aqueous physiological medium, such as gastric fluid, thereby tending to quickly release the active ingredient. Lactose, its salts and hydrates are good examples of such components. It has been observed that sometimes a portion of the fast dissolving components are formulated in a manner that results in the complete or partial encapsulation or inclusion or coating of these fast-dissolving materials in granules of slow-dissolving materials. These encapsulated materials are excluded from the calculation of the above mentioned ratio of fast-dissolving to slow dissolving components.
- A slow dissolving carrier is any binder, vehicle, or excipient that dissolves slowly over the course of hours and perhaps a day, thereby slowing the release of the active ingredient. Examples of such components are polyvinyl pyrrolidone, polyvinyl acetate, microcrystalline cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, or waxy or lipid-based tableting agents such as magnesium stearate or calcium stearate. Outer “enteric” coatings are excluded from this amount when calculating the above-mentioned ratio.
- Insoluble carriers are binders, vehicles, or excipients that are practically insoluble in physiological fluids, such as gastric fluid, and includes compounds, such as silicon dioxide and talc.
- While the exact formulation of these dosage forms can vary, it has been observed that it is advantageous to formulate them so that the ratio of fast dissolving carriers to slow dissolving carriers is from 0.30 to 0.50, and preferably from 0.35 to 0.45. A ratio of about 0.36 to 0.40 is particularly preferable.
- Dosage forms, such as capsules, tablets, and caplets that release 25 to 52% of the antibiotics within 1 hour, 53 to 89% in 2 hours, and at least 90% within 4 hours are suited to the once-a-day dosage regimen contemplated by the current inventories. More preferably, 30 to 52% of the antibiotic is released within 1 hour, 53 to 84% within 2 hours, and at least 85% within 4 hours.
- Alternatively, the oral tetracycline antibiotic may be delivered in a dosage form that releases the antibiotic in such a way that the maximum blood concentration of the antibiotic (Cmax) is reached at about 3.5 hours after administration (Tmax). In actual practice of the invention, the Cmax should be reached between 2.75 and 4.0 after administration, more preferably between 3.0 and 3.75 after administration.
- As examples of such a once-a-day formulation, one may use the following:
Quantity Component (mg) 135 mg Caplet Minocycline (as 145.8 hydrochloride) (dry weight) Lactose 107.4 Monohydrate (intragranular) Lactose 43.8 Monohydrate (extragranular) Total Lactose 151.2 Monohydrate HPMC 94 Silicon Dioxide 3 Mg. Stearate 6 45 mg Caplet Minocycline (as 48.6 hydrochloride) (dry weight) Lactose 192.2 Monohydrate (intragranular) Lactose 42.2 Monohydrate (extragranular) Total Lactose 234.40 Monohydrate HPMC 108 Silicon Dioxide 3 Mg. Stearate 6 - Each of these components is combined in a conventional fashion, compressed in a tabletting apparatus, and then provided in a conventional manner with a suitable coating, such as, without limitation Opadry II and optional coloring.
Claims (109)
Priority Applications (21)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/166,817 US7919483B2 (en) | 2005-06-24 | 2005-06-24 | Method for the treatment of acne |
PCT/US2006/023761 WO2007001961A2 (en) | 2005-06-24 | 2006-06-19 | Method for the treatment of acne |
NZ564093A NZ564093A (en) | 2005-06-24 | 2006-06-19 | Method for the treatment of acne using an oral minocycline antibiotic |
JP2008518272A JP2008543936A (en) | 2005-06-24 | 2006-06-19 | Field of the Invention Invention of Acne Treatment |
EP06773507A EP1898925A4 (en) | 2005-06-24 | 2006-06-19 | Method for the treatment of acne |
CA2613273A CA2613273C (en) | 2005-06-24 | 2006-06-19 | Method for the treatment of acne |
CNA2006800224203A CN101208097A (en) | 2005-06-24 | 2006-06-19 | Method for the treatment of acne |
AU2006262428A AU2006262428B2 (en) | 2005-06-24 | 2006-06-19 | Method for the treatment of acne |
US11/776,676 US20080182826A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,711 US20080181945A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,691 US20070275933A1 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,669 US20080182825A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/944,186 US20080182827A2 (en) | 2005-06-24 | 2007-11-21 | Method for the treatment of acne |
IL188331A IL188331A0 (en) | 2005-06-24 | 2007-12-23 | Method for the treatment of acne |
NO20080444A NO20080444L (en) | 2005-06-24 | 2008-01-23 | Method of treating acne |
ZA200802064A ZA200802064B (en) | 2005-06-24 | 2008-03-05 | Method for the treatment of acne |
US12/253,845 US7790705B2 (en) | 2005-06-24 | 2008-10-17 | Minocycline oral dosage forms for the treatment of acne |
US12/861,424 US8722650B1 (en) | 2005-06-24 | 2010-08-23 | Extended-release minocycline dosage forms |
US12/875,876 US8268804B2 (en) | 2005-06-24 | 2010-09-03 | Minocycline oral dosage forms for the treatment of acne |
US13/333,837 US20120093892A1 (en) | 2005-06-24 | 2011-12-21 | Minocycline oral dosage forms for the treatment of acne |
JP2013146709A JP5744976B2 (en) | 2005-06-24 | 2013-07-12 | Field of the Invention Invention of Acne Treatment |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/166,817 US7919483B2 (en) | 2005-06-24 | 2005-06-24 | Method for the treatment of acne |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/253,845 Continuation-In-Part US7790705B2 (en) | 2005-06-24 | 2008-10-17 | Minocycline oral dosage forms for the treatment of acne |
Related Child Applications (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/695,539 Continuation-In-Part US7544373B2 (en) | 2005-06-24 | 2007-04-02 | Minocycline oral dosage forms for the treatment of acne |
US11/776,711 Continuation US20080181945A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,669 Continuation US20080182825A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,691 Continuation US20070275933A1 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,676 Continuation US20080182826A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/944,186 Division US20080182827A2 (en) | 2005-06-24 | 2007-11-21 | Method for the treatment of acne |
US12/861,424 Continuation-In-Part US8722650B1 (en) | 2005-06-24 | 2010-08-23 | Extended-release minocycline dosage forms |
Publications (3)
Publication Number | Publication Date |
---|---|
US20060293290A1 US20060293290A1 (en) | 2006-12-28 |
US20070225262A2 true US20070225262A2 (en) | 2007-09-27 |
US7919483B2 US7919483B2 (en) | 2011-04-05 |
Family
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Family Applications (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/166,817 Active 2027-03-07 US7919483B2 (en) | 2005-06-24 | 2005-06-24 | Method for the treatment of acne |
US11/776,711 Abandoned US20080181945A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,669 Abandoned US20080182825A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,691 Abandoned US20070275933A1 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,676 Abandoned US20080182826A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/944,186 Abandoned US20080182827A2 (en) | 2005-06-24 | 2007-11-21 | Method for the treatment of acne |
Family Applications After (5)
Application Number | Title | Priority Date | Filing Date |
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US11/776,711 Abandoned US20080181945A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,669 Abandoned US20080182825A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,691 Abandoned US20070275933A1 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/776,676 Abandoned US20080182826A2 (en) | 2005-06-24 | 2007-07-12 | Method for the treatment of acne |
US11/944,186 Abandoned US20080182827A2 (en) | 2005-06-24 | 2007-11-21 | Method for the treatment of acne |
Country Status (11)
Country | Link |
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US (6) | US7919483B2 (en) |
EP (1) | EP1898925A4 (en) |
JP (2) | JP2008543936A (en) |
CN (1) | CN101208097A (en) |
AU (1) | AU2006262428B2 (en) |
CA (1) | CA2613273C (en) |
IL (1) | IL188331A0 (en) |
NO (1) | NO20080444L (en) |
NZ (1) | NZ564093A (en) |
WO (1) | WO2007001961A2 (en) |
ZA (1) | ZA200802064B (en) |
Cited By (2)
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US20060183719A1 (en) * | 2005-01-21 | 2006-08-17 | Devries Tina M | Tetracycline metal complex in a solid dosage form |
US8415331B2 (en) | 2003-07-25 | 2013-04-09 | Warner Chilcott Company, Llc | Doxycycline metal complex in a solid dosage form |
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US20110092677A1 (en) * | 2001-08-30 | 2011-04-21 | Biorexis Technology, Inc. | Modified transferin-antibody fusion proteins |
US7919483B2 (en) * | 2005-06-24 | 2011-04-05 | Medicis Pharmaceutical Corporation | Method for the treatment of acne |
US20080242642A1 (en) * | 2007-04-02 | 2008-10-02 | Medicis Pharmaceutical Corporation | Minocycline oral dosage forms for the treatment of acne |
US9192615B2 (en) | 2008-08-06 | 2015-11-24 | Medicis Pharmaceutical Corporation | Method for the treatment of acne and certain dosage forms thereof |
US8252776B2 (en) * | 2007-04-02 | 2012-08-28 | Medicis Pharmaceutical Corporation | Minocycline oral dosage forms for the treatment of acne |
US7541347B2 (en) * | 2007-04-02 | 2009-06-02 | Medicis Pharmaceutical Coropration | Minocycline oral dosage forms for the treatment of acne |
US8722650B1 (en) | 2005-06-24 | 2014-05-13 | Medicis Pharmaceutical Corporation | Extended-release minocycline dosage forms |
US20080241235A1 (en) * | 2007-04-02 | 2008-10-02 | Medicis Pharmaceutical Corporation | Minocycline oral dosage forms for the treatment of acne |
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US20100215744A1 (en) * | 2008-08-06 | 2010-08-26 | Medicis Pharmaceutical Corporation | Hydroxypropyl Substitution Used to Regulate Dissolution of a Chemical |
KR20130137696A (en) * | 2007-03-23 | 2013-12-17 | 몰레큘러 리서치 센터, 인크. | Anti-inflammatory compositions comprising tetracyclines and use thereof in therapy |
US20080241197A1 (en) * | 2007-04-02 | 2008-10-02 | Medicis Pharmaceutical Corporation | Minocycline dosage forms for the treatment of acne |
WO2008121107A1 (en) * | 2007-04-02 | 2008-10-09 | Medicis Pharmaceutical Corporation | Minocycline oral dosage forms for the treatment of acne |
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- 2006-06-19 CN CNA2006800224203A patent/CN101208097A/en active Pending
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- 2006-06-19 CA CA2613273A patent/CA2613273C/en active Active
- 2006-06-19 NZ NZ564093A patent/NZ564093A/en unknown
- 2006-06-19 EP EP06773507A patent/EP1898925A4/en not_active Withdrawn
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2007
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- 2007-07-12 US US11/776,691 patent/US20070275933A1/en not_active Abandoned
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2008
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AU2006262428A1 (en) | 2007-01-04 |
NO20080444L (en) | 2008-01-23 |
US20070259039A1 (en) | 2007-11-08 |
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AU2006262428B2 (en) | 2012-02-23 |
EP1898925A2 (en) | 2008-03-19 |
US20070254855A1 (en) | 2007-11-01 |
US20070275933A1 (en) | 2007-11-29 |
ZA200802064B (en) | 2009-09-30 |
US20080070872A1 (en) | 2008-03-20 |
WO2007001961A3 (en) | 2007-05-18 |
CA2613273C (en) | 2015-12-08 |
US20080182825A2 (en) | 2008-07-31 |
US20080182827A2 (en) | 2008-07-31 |
US20080181945A2 (en) | 2008-07-31 |
JP5744976B2 (en) | 2015-07-08 |
US20070270390A1 (en) | 2007-11-22 |
EP1898925A4 (en) | 2009-07-29 |
NZ564093A (en) | 2011-06-30 |
CA2613273A1 (en) | 2007-01-04 |
IL188331A0 (en) | 2008-08-07 |
US7919483B2 (en) | 2011-04-05 |
JP2008543936A (en) | 2008-12-04 |
WO2007001961A2 (en) | 2007-01-04 |
CN101208097A (en) | 2008-06-25 |
US20080182826A2 (en) | 2008-07-31 |
US20060293290A1 (en) | 2006-12-28 |
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