CA2222061A1 - Agents that can be administered topically for treatment and prophylaxis of alopecia - Google Patents
Agents that can be administered topically for treatment and prophylaxis of alopecia Download PDFInfo
- Publication number
- CA2222061A1 CA2222061A1 CA002222061A CA2222061A CA2222061A1 CA 2222061 A1 CA2222061 A1 CA 2222061A1 CA 002222061 A CA002222061 A CA 002222061A CA 2222061 A CA2222061 A CA 2222061A CA 2222061 A1 CA2222061 A1 CA 2222061A1
- Authority
- CA
- Canada
- Prior art keywords
- vitamin
- administered topically
- liposomes
- analogues
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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Classifications
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Abstract
The invention relates to topically applicable agents for the treatment and prevention of alopecia characterised by a content of vitamin D analogues encapsulated in liposomes.
Description
Ag~nts ~h~t C~n Be Admini~ter~d Topic~lly for Treatment and Prophylaxis of Alopecia The invention relates to agents that can be administered topically for treatment and prophylaxis of alopecia, which is characterized by a content of vitamin D analogues that are encapsulated in liposomes.
It is known that vitamin D analogues can be used for treating various forms of alopecia. Thus, agents that can be administered topically and that contain vitamin D analogues in ointments, creams, gels, or lotions are described in GB-A 2 260 903 and WO 93/00079. Since these previously known formulations, especially if they additionally contain penetration-enhancing agents, such as ethanol or propylene glycol, also have a systemic action, they also produce undesirable side-effects in addition to the desired therapeutic action. They thus also influence calcium metabolism in particular, which can lead to hypercalcemia and hypercalciuria.
The agents that can be administered topically according to the invention and contain vitamin D analogues that are encapsulated in liposomes ensure excellent effectiveness in the treatment of various forms of alopecia but, unlike the previously known agents, undesirable systemic side-effects are not observed with them.
Vitamin D analogues that are suitable for the production of the agents according to the invention are, for example, calcitriol (la,25-dihydroxyvitamin D3), calcifediol (25-hydroxyvitamin D3), calcipotriol (CAS-1128-00-9), cholecalciferol (vitamin D3) and tacalcitol (CAS-57333-96-7). Further, the vitamin D analogues that are mentioned in the above-mentioned GB-A 2 260 903 and WO 93/00079 are also suitable for the production of the agents according to the invention. As suitable vitamin D
analogues, the compounds that are described in WO 94/07853 can also be suitable, such as, for example, (5Z,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-isopropyl ester.
To encapsulate the vitamin D analogues in liposomes, the processes that are well-known to one skilled in the art can be used. Thus, for example, these active ingredients and the liposome-forming substances can be dissolved in an organic solvent, the solution can be introduced into an aqueous phase and, optionally after homogenization, the solvent can be removed by distillation. The substances or substance mixtures that form 100- to 500,000 times the amount by weight of liposomes relative to the vitamin D analogues are used.
Suitable substances that form liposomes are especially phospholipids, such as sphingomyelins, plasmalogens, phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, phosphatidylinositols and cardiolipins, or else mixtures of these lipids (Dr. Otto-Albert Neumuller: Rompps Chemie-Lexikon; Franksche Verlagshandlung [Frankch Publishing House], Stuttgart (DE), 9th Edition, 1991, 3383f) and mixtures of these phospholipids with cholesterol and/or charge carriers, such as, for example, stearylamine, stearic acid, or diacetylphosphate.
For the production of liposome suspensions, usually 0.5 to 10% by weight of phospholipid or lipid mixture relative to the aqueous phase is used. Suitable mixtures can contain up to 60%
by weight of cholesterol and up to 30% by weight of charge carrier. As a solvent, preferably ethanol, methanol, isopropanol, diethyl ether, acetone, chloroform, and mixtures of these solvents are used.
Since the lipids are sensitive to oxidation, the process is suitably carried out under an inert gas atmosphere, such as nitrogen or argon, and the aqueous liposome solutions that are obtained are stabilized by adding antioxidants, such as sodium ascorbate, tocopherol, or sodium hydrogen sulfite.
The aqueous liposome solutions can also contain additional active ingredients, such as bactericides, preservatives, and/or buffer substances.
The encapsulation of the vitamin D analogues in liposomes can be done under the same conditions as the previously known processes of this type (Pharmazie in unserer Zeit tPharmacy in our Time] 11, 1982, 97-108; Pure Appl. Chem., 53, 1981, 2241-2254). The encapsulation of the vitamin D analogues can be done both in multilamellar liposomes and in unilamellar liposomes.
In the process according to the invention, however, it is also possible, by contrast, to remove the solvent not by distillation but by using the known process of transmembrane distillation (Chem. Ing. Techn. tChem. Eng. Techn.~ 56, 1984, 514-521; J. of Membran Sci., 39, 1988, 45-51; DE-A 33 12 3S9) or pervaporation (Swiss Chem., 10, 1988, 45-51; ACS Symposium 281, 1985, 467-478; Chem. Ing. Techn., 60, 1988, s90-603).
The liposome suspensions that contain acids and are produced in this way can be diluted using water, if necessary, and/or replaced with thickeners, such as, for example, hydroxyethylcellulose, methylcellulose, Aerosil(R) (manufacturer:
Degussa AG, DE), Carbopol(R) (B. F. Goodrich Chem., USA), etc. to produce readily spreadable gels.
In contrast, however, it is also possible to evaporate the suspensions to the dry state by freeze-drying and to incorporate the residue that is obtained into an ointment base or cream.
The optimum active ingredient concentration in the finished pharmaceutical preparations depends on, of course, the type of active ingredient and the galenic preparation and must be determined in individual cases using the usual preliminary tests.
Generally, it will be sufficient if pharmaceutical preparations are used that use 0.001 to 1 mg and preferably 0.005 to 0.1 mg of vitamin D analogues per g of preparation.
The embodiments below are used to provide a more detailed explanation of the invention.
~x~mple 1 (Film method with subse~uent high-pressure homogenization) 0.9 g of PC S 100 (manufacturer: Lipoid KG, DE-Ludwigshafen), 0.1 g of cholesterol and 10 mg of (5Z,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-secocholesta-S,7,10(19),22-tetraene-25-carboxylic acid-isopropyl ester are dissolved in S0 ml of 95% ethanol. Then, in a S00 ml round-bottom flask the solution is evaporated to the dry state in a rotary evaporator, whereby a lipid film forms on the glass wall. This lipid film is dissolved with 98.9 g of twice-distilled water. Then, the liposome suspension that is obtained is homogenized with a high-pressure homogenizer (Microfluidizer(O from the Microfluid Corp.
company USA) at 400 MPA and 25~C and filtered through a 0.2 ~m filter.
The liposome suspension that is obtained contains liposomes with a mean size of 112 nm. The phosphatidylcholine content is approximately 9 mg per g; the content of encapsulated active ingredient is 0.1 mg per g.
Ex~mple 2 0.9 g of PC S 100, 0.1 g of cholesterol and 10 mg of (SZ,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-seco-cholesta-5,7,10(19),22-tetraene-25-carboxylic acid-isopropyl ester is dissolved in 50 ml of 95% ethanol.
Then, in a 500 ml round-bottom flask the solution is evaporated to the dry state in a rotary evaporator, whereby a lipid film forms on the glass wall. This lipid film is dissolved with 98.9 g of twice-distilled water. The suspension that is obtained is then subjected to high-pressure extrusion, as described in PCT/DE93/00997, whereby Nucleopore~R) membranes with decreasing pore widths of 5.0, 1.0, 0.4, 0.2, 0.1 and 0.05 ~m are used.
The liposome suspension that is obtained contains liposomes with a mean size of 94 nm and otherwise has the same properties as the preparation that is described in Example 1.
Example 3 (Production of liposome suspensions and subsequent concentration with active ingredient) o.9 g of PC S 100 and 0.1 g of DSPG, Na (manufacturer:
Sygena LTD, CH-Liestal) are dissolved in 50 ml of 95% ethanol and evaporated to the dry state, and the lipid film that is produced is dissolved with 99 g of twice-distilled water. Then, high-pressure extrusion is carried out, as described in Example 2.
50.0 g of the thus produced liposome suspension is introduced into an iodine flask, mixed with 2 mg of (5Z,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-seco-cholesta-5,7,10(19),22-tetraene-25-carboxylic acid-isopropyl ester, stirred for 18 hours at room temperature, and then filtered through a filter with a pore width of 0.2 ~m.
The liposome suspension that is thus obtained contains liposomes with a mean size of 106 nm. The phosphatidylcholine content is approximately 9.0 mg per g, and the active ingredient content is approximately 0.04 mg per g.
Example ~
(A modified reverse-phase-evaporation method) 0.5 g of PC E 100 and 10 mg of (5Z,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-isopropylester are dissolved in 100 ml of diethyl ether and mixed with 50 ml of 0.015 M aqueous tris-buffer with a pH of 7.4. Then, the two-phase mixture is homogenized in a high-pressure homogenizer (Microfluidizer(R)) at 20 Pa and 23~C. The emulsion that is produced is cleared of diethyl ether in a rotary evaporator at 4,000 Pa and 23~C, and the liposome suspension that is obtained is filtered through a 0.45 ~m filter.
The liposome suspension that is obtained contains liposomes with a mean size of 200 nm. The phosphatidylcholine content is approximately 10 mg per g; the encapsulated active ingredient content is 0.2 mg per g.
Example~ 5 ~nd 6 The liposome suspensions that are produced according to Examples 1 and 3 are mixed with 0.18% p-hydroxybenzylmethylester, 0.02% p-hydroxybenzylpropylester, and 2% hydroxyethylcellulose, and stirred for 5 minutes at 600 rpm and then briefly at 1000 rpm. Then, the mixtures are stirred for 24 hours.
The preparations have a medium-soft consistency, and their viscosity is approximately 30,000 mPa/s. The liposomes are also suspended in the aqueous phase in the preparations. They are intact.
Examples 7 and 8 (Production of a liposomal lipogel) The liposome suspensions that are produced according to Examples 1 and 3 are freeze-dried. The dried liposome cake is crushed with a percussion mill, and the powder that is produced is pulverized in portions with enough ointment base, which consists of vaseline and contains 0.02% 2,6-di-tert-butyl-4-methylphenol (= BHT) as an antioxidant, that the active ingredient concentration in the finished ointment is approximately 0.05 mg per g.
It is known that vitamin D analogues can be used for treating various forms of alopecia. Thus, agents that can be administered topically and that contain vitamin D analogues in ointments, creams, gels, or lotions are described in GB-A 2 260 903 and WO 93/00079. Since these previously known formulations, especially if they additionally contain penetration-enhancing agents, such as ethanol or propylene glycol, also have a systemic action, they also produce undesirable side-effects in addition to the desired therapeutic action. They thus also influence calcium metabolism in particular, which can lead to hypercalcemia and hypercalciuria.
The agents that can be administered topically according to the invention and contain vitamin D analogues that are encapsulated in liposomes ensure excellent effectiveness in the treatment of various forms of alopecia but, unlike the previously known agents, undesirable systemic side-effects are not observed with them.
Vitamin D analogues that are suitable for the production of the agents according to the invention are, for example, calcitriol (la,25-dihydroxyvitamin D3), calcifediol (25-hydroxyvitamin D3), calcipotriol (CAS-1128-00-9), cholecalciferol (vitamin D3) and tacalcitol (CAS-57333-96-7). Further, the vitamin D analogues that are mentioned in the above-mentioned GB-A 2 260 903 and WO 93/00079 are also suitable for the production of the agents according to the invention. As suitable vitamin D
analogues, the compounds that are described in WO 94/07853 can also be suitable, such as, for example, (5Z,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-isopropyl ester.
To encapsulate the vitamin D analogues in liposomes, the processes that are well-known to one skilled in the art can be used. Thus, for example, these active ingredients and the liposome-forming substances can be dissolved in an organic solvent, the solution can be introduced into an aqueous phase and, optionally after homogenization, the solvent can be removed by distillation. The substances or substance mixtures that form 100- to 500,000 times the amount by weight of liposomes relative to the vitamin D analogues are used.
Suitable substances that form liposomes are especially phospholipids, such as sphingomyelins, plasmalogens, phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, phosphatidylinositols and cardiolipins, or else mixtures of these lipids (Dr. Otto-Albert Neumuller: Rompps Chemie-Lexikon; Franksche Verlagshandlung [Frankch Publishing House], Stuttgart (DE), 9th Edition, 1991, 3383f) and mixtures of these phospholipids with cholesterol and/or charge carriers, such as, for example, stearylamine, stearic acid, or diacetylphosphate.
For the production of liposome suspensions, usually 0.5 to 10% by weight of phospholipid or lipid mixture relative to the aqueous phase is used. Suitable mixtures can contain up to 60%
by weight of cholesterol and up to 30% by weight of charge carrier. As a solvent, preferably ethanol, methanol, isopropanol, diethyl ether, acetone, chloroform, and mixtures of these solvents are used.
Since the lipids are sensitive to oxidation, the process is suitably carried out under an inert gas atmosphere, such as nitrogen or argon, and the aqueous liposome solutions that are obtained are stabilized by adding antioxidants, such as sodium ascorbate, tocopherol, or sodium hydrogen sulfite.
The aqueous liposome solutions can also contain additional active ingredients, such as bactericides, preservatives, and/or buffer substances.
The encapsulation of the vitamin D analogues in liposomes can be done under the same conditions as the previously known processes of this type (Pharmazie in unserer Zeit tPharmacy in our Time] 11, 1982, 97-108; Pure Appl. Chem., 53, 1981, 2241-2254). The encapsulation of the vitamin D analogues can be done both in multilamellar liposomes and in unilamellar liposomes.
In the process according to the invention, however, it is also possible, by contrast, to remove the solvent not by distillation but by using the known process of transmembrane distillation (Chem. Ing. Techn. tChem. Eng. Techn.~ 56, 1984, 514-521; J. of Membran Sci., 39, 1988, 45-51; DE-A 33 12 3S9) or pervaporation (Swiss Chem., 10, 1988, 45-51; ACS Symposium 281, 1985, 467-478; Chem. Ing. Techn., 60, 1988, s90-603).
The liposome suspensions that contain acids and are produced in this way can be diluted using water, if necessary, and/or replaced with thickeners, such as, for example, hydroxyethylcellulose, methylcellulose, Aerosil(R) (manufacturer:
Degussa AG, DE), Carbopol(R) (B. F. Goodrich Chem., USA), etc. to produce readily spreadable gels.
In contrast, however, it is also possible to evaporate the suspensions to the dry state by freeze-drying and to incorporate the residue that is obtained into an ointment base or cream.
The optimum active ingredient concentration in the finished pharmaceutical preparations depends on, of course, the type of active ingredient and the galenic preparation and must be determined in individual cases using the usual preliminary tests.
Generally, it will be sufficient if pharmaceutical preparations are used that use 0.001 to 1 mg and preferably 0.005 to 0.1 mg of vitamin D analogues per g of preparation.
The embodiments below are used to provide a more detailed explanation of the invention.
~x~mple 1 (Film method with subse~uent high-pressure homogenization) 0.9 g of PC S 100 (manufacturer: Lipoid KG, DE-Ludwigshafen), 0.1 g of cholesterol and 10 mg of (5Z,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-secocholesta-S,7,10(19),22-tetraene-25-carboxylic acid-isopropyl ester are dissolved in S0 ml of 95% ethanol. Then, in a S00 ml round-bottom flask the solution is evaporated to the dry state in a rotary evaporator, whereby a lipid film forms on the glass wall. This lipid film is dissolved with 98.9 g of twice-distilled water. Then, the liposome suspension that is obtained is homogenized with a high-pressure homogenizer (Microfluidizer(O from the Microfluid Corp.
company USA) at 400 MPA and 25~C and filtered through a 0.2 ~m filter.
The liposome suspension that is obtained contains liposomes with a mean size of 112 nm. The phosphatidylcholine content is approximately 9 mg per g; the content of encapsulated active ingredient is 0.1 mg per g.
Ex~mple 2 0.9 g of PC S 100, 0.1 g of cholesterol and 10 mg of (SZ,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-seco-cholesta-5,7,10(19),22-tetraene-25-carboxylic acid-isopropyl ester is dissolved in 50 ml of 95% ethanol.
Then, in a 500 ml round-bottom flask the solution is evaporated to the dry state in a rotary evaporator, whereby a lipid film forms on the glass wall. This lipid film is dissolved with 98.9 g of twice-distilled water. The suspension that is obtained is then subjected to high-pressure extrusion, as described in PCT/DE93/00997, whereby Nucleopore~R) membranes with decreasing pore widths of 5.0, 1.0, 0.4, 0.2, 0.1 and 0.05 ~m are used.
The liposome suspension that is obtained contains liposomes with a mean size of 94 nm and otherwise has the same properties as the preparation that is described in Example 1.
Example 3 (Production of liposome suspensions and subsequent concentration with active ingredient) o.9 g of PC S 100 and 0.1 g of DSPG, Na (manufacturer:
Sygena LTD, CH-Liestal) are dissolved in 50 ml of 95% ethanol and evaporated to the dry state, and the lipid film that is produced is dissolved with 99 g of twice-distilled water. Then, high-pressure extrusion is carried out, as described in Example 2.
50.0 g of the thus produced liposome suspension is introduced into an iodine flask, mixed with 2 mg of (5Z,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-seco-cholesta-5,7,10(19),22-tetraene-25-carboxylic acid-isopropyl ester, stirred for 18 hours at room temperature, and then filtered through a filter with a pore width of 0.2 ~m.
The liposome suspension that is thus obtained contains liposomes with a mean size of 106 nm. The phosphatidylcholine content is approximately 9.0 mg per g, and the active ingredient content is approximately 0.04 mg per g.
Example ~
(A modified reverse-phase-evaporation method) 0.5 g of PC E 100 and 10 mg of (5Z,7E,22E)-(lS,3R,24R)-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-isopropylester are dissolved in 100 ml of diethyl ether and mixed with 50 ml of 0.015 M aqueous tris-buffer with a pH of 7.4. Then, the two-phase mixture is homogenized in a high-pressure homogenizer (Microfluidizer(R)) at 20 Pa and 23~C. The emulsion that is produced is cleared of diethyl ether in a rotary evaporator at 4,000 Pa and 23~C, and the liposome suspension that is obtained is filtered through a 0.45 ~m filter.
The liposome suspension that is obtained contains liposomes with a mean size of 200 nm. The phosphatidylcholine content is approximately 10 mg per g; the encapsulated active ingredient content is 0.2 mg per g.
Example~ 5 ~nd 6 The liposome suspensions that are produced according to Examples 1 and 3 are mixed with 0.18% p-hydroxybenzylmethylester, 0.02% p-hydroxybenzylpropylester, and 2% hydroxyethylcellulose, and stirred for 5 minutes at 600 rpm and then briefly at 1000 rpm. Then, the mixtures are stirred for 24 hours.
The preparations have a medium-soft consistency, and their viscosity is approximately 30,000 mPa/s. The liposomes are also suspended in the aqueous phase in the preparations. They are intact.
Examples 7 and 8 (Production of a liposomal lipogel) The liposome suspensions that are produced according to Examples 1 and 3 are freeze-dried. The dried liposome cake is crushed with a percussion mill, and the powder that is produced is pulverized in portions with enough ointment base, which consists of vaseline and contains 0.02% 2,6-di-tert-butyl-4-methylphenol (= BHT) as an antioxidant, that the active ingredient concentration in the finished ointment is approximately 0.05 mg per g.
Claims (4)
1. An agent that can be administered topically for treatment and prophylaxis of alopecia based on vitamin D analogues that are encapsulated in liposomes, characterized in that the encapsulated vitamin D analogue is calcitriol, calcifediol, calcipotriol, cholecalciferol, tacalcitol or (5Z, 7E, 22E)-(1S, 3R, 24R)-1,3, 24-trihydroxy-9,10-secocholesta-5,7,10 (19), 22-tetraene-25-carboxylic acid-isopropyl ester.
2. An agent that can be administered topically for treatment and prophylaxis of alopecia based on vitamin D analogues that are encapsulated in liposomes, wherein the encapsulated vitamin D analogue is (5Z, 7E, 22E)-(1S, 3R,24R)-1,3,24-trihydroxy-9,10-secocholesta-5,7,10 (19), 22-tetraene-25-carboxylic acid isopropylester.
3. An agent that can be administered topically according to claim 1 or 2, wherein the agent contains 0.001 to 1 mg of vitamin D analogue per g of preparation.
4. An agent that can be administered topically according to claim 1 or 2, wherein the agent contains 0.005 to 0.1 mg of vitamin D analogue per g of preparation.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19519273.7 | 1995-05-22 | ||
| DE19519273A DE19519273A1 (en) | 1995-05-22 | 1995-05-22 | Topical agents for the treatment and prophylaxis of alopecia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2222061A1 true CA2222061A1 (en) | 1996-11-28 |
Family
ID=7762883
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002222061A Abandoned CA2222061A1 (en) | 1995-05-22 | 1996-05-22 | Agents that can be administered topically for treatment and prophylaxis of alopecia |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0827395A1 (en) |
| JP (1) | JPH11505262A (en) |
| KR (1) | KR19990021864A (en) |
| AU (1) | AU5819996A (en) |
| CA (1) | CA2222061A1 (en) |
| DE (1) | DE19519273A1 (en) |
| WO (1) | WO1996037193A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9375388B2 (en) | 2011-09-23 | 2016-06-28 | Indian Institute Of Technology, Bombay | Nanoparticle based cosmetic composition |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0892638B1 (en) * | 1996-04-04 | 2002-11-13 | Cilag AG | Liposome-based topical vitamin d formulation |
| US20030095937A1 (en) * | 2001-10-02 | 2003-05-22 | Koeffler H. Philip | Method for stimulating hair growth by administering vitamin D analogs |
| US20030219465A1 (en) * | 2002-05-23 | 2003-11-27 | Suresh Kumar Gidwani | Composition for delivery of dithranol |
| JP5978130B2 (en) | 2009-08-14 | 2016-08-24 | バーグ エルエルシー | Vitamin D3 and analogs thereof for treating alopecia |
| FR3017290B1 (en) * | 2014-02-10 | 2017-05-12 | Dermaconcept Jmc | COMPOSITION FOR CONTROLLING THE FALL OF HAIR |
| MX2021006750A (en) | 2018-12-06 | 2021-11-17 | Lipicare Life Sciences Ltd | Vitamin d micro-emulsions and uses thereof. |
| AU2020279960A1 (en) * | 2019-05-17 | 2021-12-23 | The Trustees Of The University Of Pennsylvania | Methods and compositions for treating obesity and/or skin disorders |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5116605A (en) * | 1989-03-09 | 1992-05-26 | Alt John P | Composition and skin treatment method therewith for mitigating acne and male-pattern baldness |
| US5401731A (en) * | 1989-06-29 | 1995-03-28 | Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Productionsaktieselskab) | Vitamin D analogues |
| GB8915770D0 (en) * | 1989-07-10 | 1989-08-31 | Leo Pharm Prod Ltd | Chemical compounds |
| GB9007236D0 (en) * | 1990-03-30 | 1990-05-30 | Leo Pharm Prod Ltd | Chemical compounds |
| GB9017890D0 (en) * | 1990-08-15 | 1990-09-26 | Leo Pharm Prod Ltd | Chemical compounds i |
| DK0664287T3 (en) * | 1994-01-20 | 1999-04-19 | Duphar Int Res | Vitamin D compounds and methods for preparing them |
-
1995
- 1995-05-22 DE DE19519273A patent/DE19519273A1/en not_active Withdrawn
-
1996
- 1996-05-22 WO PCT/EP1996/002195 patent/WO1996037193A1/en not_active Application Discontinuation
- 1996-05-22 CA CA002222061A patent/CA2222061A1/en not_active Abandoned
- 1996-05-22 KR KR1019970708338A patent/KR19990021864A/en not_active Application Discontinuation
- 1996-05-22 AU AU58199/96A patent/AU5819996A/en not_active Abandoned
- 1996-05-22 JP JP8535377A patent/JPH11505262A/en active Pending
- 1996-05-22 EP EP96919796A patent/EP0827395A1/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9375388B2 (en) | 2011-09-23 | 2016-06-28 | Indian Institute Of Technology, Bombay | Nanoparticle based cosmetic composition |
Also Published As
| Publication number | Publication date |
|---|---|
| AU5819996A (en) | 1996-12-11 |
| JPH11505262A (en) | 1999-05-18 |
| DE19519273A1 (en) | 1996-11-28 |
| WO1996037193A1 (en) | 1996-11-28 |
| EP0827395A1 (en) | 1998-03-11 |
| KR19990021864A (en) | 1999-03-25 |
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