WO2009136677A1 - Gel composition comprising minoxidil - Google Patents

Gel composition comprising minoxidil Download PDF

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Publication number
WO2009136677A1
WO2009136677A1 PCT/KR2008/002982 KR2008002982W WO2009136677A1 WO 2009136677 A1 WO2009136677 A1 WO 2009136677A1 KR 2008002982 W KR2008002982 W KR 2008002982W WO 2009136677 A1 WO2009136677 A1 WO 2009136677A1
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Prior art keywords
minoxidil
gel composition
gel
thickener
glycerin
Prior art date
Application number
PCT/KR2008/002982
Other languages
French (fr)
Inventor
Kyu-Hyun Lee
Sung-Hoon Kam
Ku-Seo Kim
Original Assignee
Hyundai Pharm Co., Ltd.
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Publication date
Application filed by Hyundai Pharm Co., Ltd. filed Critical Hyundai Pharm Co., Ltd.
Priority to CN2008801298735A priority Critical patent/CN102065839A/en
Publication of WO2009136677A1 publication Critical patent/WO2009136677A1/en

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Classifications

    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone

Definitions

  • the present invention relates to a gel composition comprising minoxidil, more specifically to a gel composition that can maintain a stable gel phase while dissolving a high concentration of minoxidil.
  • Minoxidil 2,4-diamino-6-piperidinylpyrimidine-3-oxide is an active ingredient widely used for treatment or prevention of hypertension or androgenetic alopecia.
  • a method of using minoxidil for hair growth or treatment of male or female- pattern baldness, and its topical preparation are disclosed in U.S. Patent No. 4,139,619 and No. 4,596,812, etc.
  • a topical preparation comprising minoxidil can be of various form including liquid, gel or suspension, etc.
  • U.S. Patent No. 5,225,189 discloses a gel composition
  • a gel composition comprising an active ingredient minoxidil, water, a carbomer thickener, pharmaceutically acceptable glycol (for example, propyleneglycol), ethanol or isopropanol, and amine that can be dissolved in water or alcohol.
  • minoxidil is solubilized with glycol such as propyleneglycol, the preparation is provided in the form of a gel with the carbomer thickener.
  • WO 02/11698 discloses a gel composition
  • a gel composition comprising an active ingredient minoxidil, a non-carbomer thickener, and a pharmaceutically acceptable solvent (for example, glycol such as propyleneglycol and alcohol such as ethanol, etc.).
  • a pharmaceutically acceptable solvent for example, glycol such as propyleneglycol and alcohol such as ethanol, etc.
  • minoxidil is solubilized with a solvent such as glycol (for example, propyleneglycol), and the composition is provided in the form of a gel with the non- carbomer thickener.
  • the solubilization of minoxidil with propyleneglycol is limited.
  • the gel topical preparation of the prior art is difficult to maintain a stable gel phase in high concentration of minoxidil dissolved with 3 wt% or more, and thus, cannot exhibit sufficient treatment effect on alopecia, etc.
  • propyleneglycol exhibits relatively high skin irritations, therefore if identical topical preparation of gel form was applied to scalp or other areas, for treatment of alopecia, may cause side effects.
  • the present invention provides a gel composition that can maintain a stable gel phase while dissolving a higher concentration of minoxidil, and reduce skin irritations.
  • the present invention provides a gel composition comprising an effective amount of minoxidil, a thickener, and an aqueous solvent containing glycerin.
  • the minoxidil may be comprised in an amount of 1 to 10 wt%.
  • the thickener may comprise a carbomer thickener.
  • the gel composition preferably comprises 1 to 10 wt% of the minoxidil, 0.1 to 2 wt% of the thickener, and 89 to 98 wt% of the aqueous solvent containing glycerin.
  • the glycerin may be comprised in an amount of 10 to 30 wt% of the total gel composition.
  • the aqueous solvent may comprise glycerin, water and ethanol, wherein the weight ratio of water to ethanol (water : ethanol) is preferably 1 : 2 to 1 : 4.
  • the pH of the gel composition is preferably 7.5 to 9.0, and for this, the composition may have additional amine-based pH controllers.
  • a gel composition comprising an effective amount of minoxidil, a thickener, and an aqueous solvent containing glycerin is provided.
  • a higher concentration, for example, 3-5 wt% of minoxidil can be dissolved in an aqueous solvent, and especially, even if a thickener for providing a gel type composition is combined, minoxidil dissolved in the aqueous solvent does not generate white precipitate and can maintain a dissolved transparent gel phase. Therefore, according to one embodiment of the invention, a gel composition comprising minoxidil that can maintain a stable gel phase while dissolving a higher concentration of minoxidil is provided.
  • the gel composition can solubilize minoxidil with glycerin that has low skin irritation suitable for cosmetic usages, without using propyleneglycol having relatively high skin irritation, and thus, skin irritations and side effects due to the gel composition can be largely reduced. Moreover, the gel composition can stay on the applied area such as scalp for sufficient time compared to liquid type topical preparations, thus sufficiently increase absorption and bioavailability of minoxidil.
  • the gel composition allows a higher concentration of minoxidil to stay on the applied area such as scalp for a sufficient time to largely increase absorption and bioavailability of minoxidil, and increases treatment effect on alopecia, etc. Also, the gel composition can reduce skin irritation or other side effects caused by solvent.
  • the gel composition may comprise the active ingredient minoxidil in an amount between 1 to 1Og, preferably 3 to 7g, and most preferably 5g per 10Og. Thus, the gel composition can be preferably used for treatment or prevention of alopecia, etc.
  • a carbomer thickener is preferably used as the thickener used in the gel composition.
  • the examples of the carbormer thickener include commercially available Carbopol 940.
  • the thickener gives viscosity to render the composition in gel form, and the carbomer thickener allows the composition to maintain more stable gel phase.
  • the gel composition preferably comprises 1 to 10 wt% of minoxidil, 0.1 to 2 wt% of the thickener, and 89 to 98 wt% of the aqueous solvent containing glycerin. Also, the composition preferably comprises the glycerin in an amount of 10 to 30 wt%, more preferably, 12 to 24 wt% of the total gel composition.
  • the gel composition comprises each ingredient, especially the active ingredient minoxidil and the aqueous solvent containing glycerin in the above content range, it can maintain a stable gel phase while dissolving a higher concentration of minoxidil in the aqueous solvent. If the above range is not satisfied, especially the amount of the glycerin is too high or too low, it is difficult to dissolve a high concentration of minoxidil and maintain stable gel phase, also causes problems such as white precipitate formation.
  • the aqueous solvent containing glycerin may comprise water with glycerin, and it may have an additional alcohol solvent, for example, ethanol.
  • the weight ratio of water to alcohol solvent is preferably 1 : 2 to 1 : 4, more preferably 1 : 2.5 to 1 : 3.75.
  • aqueous solvent comprises glycerin
  • water and alcohol solvent in the above weight ratio, a higher concentration of minoxidil can be dissolved, and the gel composition can maintain a stable gel phase. If the weight ratio of water to ethanol is not satisfied, it is difficult to dissolve a high concentration of minoxidil and the carbomer thickener may generate thick mass, thus making the gel composition difficult to maintain preferable gel phase.
  • the pH of the gel composition is preferably 7.5 to 9.0, and the composition may further comprise an amine-based pH controller, such as, triethanolamine.
  • the present inventors found that when the gel composition shows such a weak basic pH, more stable gel phase can be formed and maintained while dissolving a high concentration of minoxidil, and the composition has appropriate viscosity (for example, 8000 ⁇ 14000cP) to stay on the applied area such as scalp, for a sufficient time, which makes the gel composition can be more effectively used for treatment of alopecia, etc.
  • appropriate viscosity for example, 8000 ⁇ 14000cP
  • the gel composition according to one embodiment of the invention can maintain stable gel phase while dissolving a higher concentration of minoxidil without causing skin irritation.
  • the gel composition allows higher concentration of minoxidil to stay on the applied area such as scalp for a sufficient time, increasing absorption and bioavailability of minoxidil, therefore, increasing treatment effect of minoxidil on alopecia.
  • the gel composition can be prepared by a common gel composition preparation method as follows. First, a thickener is mixed with an alcohol solvent, etc. to dissolve the thickener, and the solution is agitated for approximately 10 to 20 minutes to prepare the thickener solution.
  • glycerin and an aqueous solvent for example, water and an alcohol solvent
  • aqueous solvent for example, water and an alcohol solvent
  • active ingredient minoxidil is added and the solution is agitated for approximately 30 to 50 minutes to prepare minoxidil solution.
  • higher concentration of minoxidil is dissolved by the action of glycerin.
  • the minoxidil solution and the thickener solution are mixed and the mixture is agitated for approximately 50 to 70 minutes, and an amine-based pH controller such as triethanolamine is added and the mixture is agitated for approximately 1 to 10 minutes to control the pH.
  • an amine-based pH controller such as triethanolamine
  • the gel composition that can maintain a stable gel phase while dissolving higher concentration of minoxidil can be prepared.
  • the gel composition that can maintain stable gel phase while dissolving higher concentration of minoxidil is provided.
  • the gel composition can stay on the applied area, such as scalp, for a sufficient time while comprising higher concentration of minoxidil, thus, can be more effectively used for the treatment of alopecia, etc.
  • Example 1 and Comparative Examples 1 to 4 Preparation of gel composition comprising minoxidil (selection of optimum solvent)
  • an active ingredient minoxidil a thickener (Carbopol 940), an amine-based pH controller, ethanol, purified water and a solvent (example 1 : glycerin, comparative examples 1 to 4: other solvents) were mixed to prepare the gel composition comprising minoxidil.
  • glycerin concentrated glycerin comprising glycerin in the concentration of 98% or more was used, and as the amine-based pH controller, triethanolamine was used.
  • the ingredients were mixed in the propeller mixer (model name: IKA - RW20DZM.n)(agi-mixer), and the mixer was operated at 600 ⁇ 800rpm.
  • the method for mixing each ingredient and preparing a gel composition is as follows.
  • a thickener was mixed with ethanol to dissolve the thickener, and the solution was agitated for approximately 10 minutes to prepare a thickener solution. Then, a selected solvent, water and ethanol were mixed and the solution was agitated for approximately 10 minutes, and minoxidil was added then, the solution was agitated for approximately 30 minutes to prepare a minoxidil solution. The minoxidil solution and the thickener solution were mixed then the mixed solution was agitated for approximately 50 minutes, and an amine-based pH controller was added and the mixture was agitated for approximately 2 minutes. Thereby, the gel compositions of Example 1 and Comparative Examples 1 through 4 were prepared. [Table 1]
  • Example 1 generated transparent and stable gel phase while completely dissolving a high concentration of 5 wt% of minoxidil.
  • the gel compositions of Comparative Example 1 through 4 failed to dissolve a high concentration of minoxidil and generated white precipitate thus could not be provided as transparent gel phase.
  • compositions described in the following Tables 3 and 4 an active ingredient minoxidil and a thickener (Carbopol 940), a pH controller (alkalizer or acidifier), ethanol, purified water and glycerin(concentrated glycerin) were mixed to prepare the gel composition.
  • a thickener Carbopol 940
  • a pH controller alkalizer or acidifier
  • ethanol purified water
  • glycerin(concentrated glycerin) were mixed to prepare the gel composition.

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Abstract

The present invention relates to a gel composition comprising minoxidil that can maintain stable gel phase while dissolving a high concentration of minoxidil. The gel composition comprises an effective amount of minoxidil, a thickener, and an aqueous solvent containing glycerin.

Description

TITLE OF THE INVENTION
GEL COMPOSITION COMPRISING MINOXIDIL
FIELD OF THE INVENTION The present invention relates to a gel composition comprising minoxidil, more specifically to a gel composition that can maintain a stable gel phase while dissolving a high concentration of minoxidil.
BACKGROUND OF THE INVENTION Minoxidil, 2,4-diamino-6-piperidinylpyrimidine-3-oxide is an active ingredient widely used for treatment or prevention of hypertension or androgenetic alopecia. Especially, a method of using minoxidil for hair growth or treatment of male or female- pattern baldness, and its topical preparation are disclosed in U.S. Patent No. 4,139,619 and No. 4,596,812, etc. A topical preparation comprising minoxidil can be of various form including liquid, gel or suspension, etc.
However, in the case of a topical preparation in the form of a suspension where the active ingredient minoxidil is not dissolved in a medium and is simply suspended, the active ingredient is not properly absorbed into body thus cannot fully exhibit its treatment effect. Also, in the case of a topical preparation in the form of liquid, since it is difficult to stay on the applied area for a sufficient time, the active ingredient minoxidil cannot be absorbed in a sufficient amount thus decreasing bioavailability, and therefore, treatment effect of minoxidil cannot be sufficiently exhibited.
Meanwhile, in the case of a topical preparation in the form of gel, it can stay on the applied area such as scalp for a sufficient time, thus increasing absorption and bioavailability of minoxidil and exhibiting more improved treatment effect.
Therefore, there have been various attempts to provide a topical preparation comprising minoxidil in the form of a gel.
For example, U.S. Patent No. 5,225,189 discloses a gel composition comprising an active ingredient minoxidil, water, a carbomer thickener, pharmaceutically acceptable glycol (for example, propyleneglycol), ethanol or isopropanol, and amine that can be dissolved in water or alcohol. In the gel composition, minoxidil is solubilized with glycol such as propyleneglycol, the preparation is provided in the form of a gel with the carbomer thickener.
And, WO 02/11698 discloses a gel composition comprising an active ingredient minoxidil, a non-carbomer thickener, and a pharmaceutically acceptable solvent (for example, glycol such as propyleneglycol and alcohol such as ethanol, etc.). In the composition, minoxidil is solubilized with a solvent such as glycol (for example, propyleneglycol), and the composition is provided in the form of a gel with the non- carbomer thickener.
However, in the topical preparation of gel form of the prior art, although minoxidil is solubilized with a solvent such as propyleneglycol to some extent, the solubilization of minoxidil with propyleneglycol is limited. For an instance, the gel topical preparation of the prior art is difficult to maintain a stable gel phase in high concentration of minoxidil dissolved with 3 wt% or more, and thus, cannot exhibit sufficient treatment effect on alopecia, etc.
Since propyleneglycol exhibits relatively high skin irritations, therefore if identical topical preparation of gel form was applied to scalp or other areas, for treatment of alopecia, may cause side effects.
SUMMARY OF THE INVENTION
The present invention provides a gel composition that can maintain a stable gel phase while dissolving a higher concentration of minoxidil, and reduce skin irritations. The present invention provides a gel composition comprising an effective amount of minoxidil, a thickener, and an aqueous solvent containing glycerin.
In the gel composition, the minoxidil may be comprised in an amount of 1 to 10 wt%.
And, the thickener may comprise a carbomer thickener. And, the gel composition preferably comprises 1 to 10 wt% of the minoxidil, 0.1 to 2 wt% of the thickener, and 89 to 98 wt% of the aqueous solvent containing glycerin. The glycerin may be comprised in an amount of 10 to 30 wt% of the total gel composition. And, the aqueous solvent may comprise glycerin, water and ethanol, wherein the weight ratio of water to ethanol (water : ethanol) is preferably 1 : 2 to 1 : 4.
The pH of the gel composition is preferably 7.5 to 9.0, and for this, the composition may have additional amine-based pH controllers.
DETAILED DESCRIPTION OF THE EMBODIMENTS
The present invention will now be explained in more detail according to one embodiment thereof. However, it is only to illustrate the present invention, and, the scope of the invention is not limited, but various modifications can be made within the scope of the invention also. The term "comprising (comprise)" or "containing (contain)" herein means comprising an element (or an ingredient) without specific limitation, and it should not be interpreted as excluding other elements (or ingredients).
According to one embodiment of the invention, a gel composition comprising an effective amount of minoxidil, a thickener, and an aqueous solvent containing glycerin is provided.
As the results of experiments, the present inventors found that if glycerin is used, a higher concentration, for example, 3-5 wt% of minoxidil can be dissolved in an aqueous solvent, and especially, even if a thickener for providing a gel type composition is combined, minoxidil dissolved in the aqueous solvent does not generate white precipitate and can maintain a dissolved transparent gel phase. Therefore, according to one embodiment of the invention, a gel composition comprising minoxidil that can maintain a stable gel phase while dissolving a higher concentration of minoxidil is provided.
The gel composition can solubilize minoxidil with glycerin that has low skin irritation suitable for cosmetic usages, without using propyleneglycol having relatively high skin irritation, and thus, skin irritations and side effects due to the gel composition can be largely reduced. Moreover, the gel composition can stay on the applied area such as scalp for sufficient time compared to liquid type topical preparations, thus sufficiently increase absorption and bioavailability of minoxidil.
Therefore, the gel composition allows a higher concentration of minoxidil to stay on the applied area such as scalp for a sufficient time to largely increase absorption and bioavailability of minoxidil, and increases treatment effect on alopecia, etc. Also, the gel composition can reduce skin irritation or other side effects caused by solvent. The gel composition may comprise the active ingredient minoxidil in an amount between 1 to 1Og, preferably 3 to 7g, and most preferably 5g per 10Og. Thus, the gel composition can be preferably used for treatment or prevention of alopecia, etc.
As the thickener used in the gel composition, a carbomer thickener is preferably used. The examples of the carbormer thickener include commercially available Carbopol 940. The thickener gives viscosity to render the composition in gel form, and the carbomer thickener allows the composition to maintain more stable gel phase.
The gel composition preferably comprises 1 to 10 wt% of minoxidil, 0.1 to 2 wt% of the thickener, and 89 to 98 wt% of the aqueous solvent containing glycerin. Also, the composition preferably comprises the glycerin in an amount of 10 to 30 wt%, more preferably, 12 to 24 wt% of the total gel composition.
In case the gel composition comprises each ingredient, especially the active ingredient minoxidil and the aqueous solvent containing glycerin in the above content range, it can maintain a stable gel phase while dissolving a higher concentration of minoxidil in the aqueous solvent. If the above range is not satisfied, especially the amount of the glycerin is too high or too low, it is difficult to dissolve a high concentration of minoxidil and maintain stable gel phase, also causes problems such as white precipitate formation.
The aqueous solvent containing glycerin may comprise water with glycerin, and it may have an additional alcohol solvent, for example, ethanol. The weight ratio of water to alcohol solvent (water : alcohol solvent, for example, water : ethanol) is preferably 1 : 2 to 1 : 4, more preferably 1 : 2.5 to 1 : 3.75.
In case the aqueous solvent comprises glycerin, water and alcohol solvent in the above weight ratio, a higher concentration of minoxidil can be dissolved, and the gel composition can maintain a stable gel phase. If the weight ratio of water to ethanol is not satisfied, it is difficult to dissolve a high concentration of minoxidil and the carbomer thickener may generate thick mass, thus making the gel composition difficult to maintain preferable gel phase.
The pH of the gel composition is preferably 7.5 to 9.0, and the composition may further comprise an amine-based pH controller, such as, triethanolamine.
As results of the experiments, the present inventors found that when the gel composition shows such a weak basic pH, more stable gel phase can be formed and maintained while dissolving a high concentration of minoxidil, and the composition has appropriate viscosity (for example, 8000~14000cP) to stay on the applied area such as scalp, for a sufficient time, which makes the gel composition can be more effectively used for treatment of alopecia, etc.
As described above, the gel composition according to one embodiment of the invention can maintain stable gel phase while dissolving a higher concentration of minoxidil without causing skin irritation. Thus, the gel composition allows higher concentration of minoxidil to stay on the applied area such as scalp for a sufficient time, increasing absorption and bioavailability of minoxidil, therefore, increasing treatment effect of minoxidil on alopecia.
The gel composition can be prepared by a common gel composition preparation method as follows. First, a thickener is mixed with an alcohol solvent, etc. to dissolve the thickener, and the solution is agitated for approximately 10 to 20 minutes to prepare the thickener solution.
Then, glycerin and an aqueous solvent (for example, water and an alcohol solvent) are mixed and the solution is agitated for approximately 10 to 20 minutes, and active ingredient minoxidil is added and the solution is agitated for approximately 30 to 50 minutes to prepare minoxidil solution. At this stage, higher concentration of minoxidil is dissolved by the action of glycerin.
Subsequently, the minoxidil solution and the thickener solution are mixed and the mixture is agitated for approximately 50 to 70 minutes, and an amine-based pH controller such as triethanolamine is added and the mixture is agitated for approximately 1 to 10 minutes to control the pH.
By the above method, the gel composition that can maintain a stable gel phase while dissolving higher concentration of minoxidil can be prepared. As mentioned above, according to one embodiment of the invention, the gel composition that can maintain stable gel phase while dissolving higher concentration of minoxidil is provided. The gel composition can stay on the applied area, such as scalp, for a sufficient time while comprising higher concentration of minoxidil, thus, can be more effectively used for the treatment of alopecia, etc. EXAMPLES
The present invention will be explained with reference to the following examples. However, these are only to illustrate the present invention, and the scope of the invention is not limited thereto.
Example 1 and Comparative Examples 1 to 4: Preparation of gel composition comprising minoxidil (selection of optimum solvent)
With the composition as described in the following Table 1, an active ingredient minoxidil, a thickener (Carbopol 940), an amine-based pH controller, ethanol, purified water and a solvent (example 1 : glycerin, comparative examples 1 to 4: other solvents) were mixed to prepare the gel composition comprising minoxidil.
As the glycerin, concentrated glycerin comprising glycerin in the concentration of 98% or more was used, and as the amine-based pH controller, triethanolamine was used.
The ingredients were mixed in the propeller mixer (model name: IKA - RW20DZM.n)(agi-mixer), and the mixer was operated at 600~800rpm.
The method for mixing each ingredient and preparing a gel composition is as follows.
First, a thickener was mixed with ethanol to dissolve the thickener, and the solution was agitated for approximately 10 minutes to prepare a thickener solution. Then, a selected solvent, water and ethanol were mixed and the solution was agitated for approximately 10 minutes, and minoxidil was added then, the solution was agitated for approximately 30 minutes to prepare a minoxidil solution. The minoxidil solution and the thickener solution were mixed then the mixed solution was agitated for approximately 50 minutes, and an amine-based pH controller was added and the mixture was agitated for approximately 2 minutes. Thereby, the gel compositions of Example 1 and Comparative Examples 1 through 4 were prepared. [Table 1]
Figure imgf000008_0001
Figure imgf000009_0001
* In the above Table 1, "Labrafil M 1944 CS" represents "oleoyl macrogolglyceride" which is a surfactant, and "Cremorphor ELP" represents "peg-35 castor oil" which is used as a solubilizer.
After preparing the gel composition of the Example 1 and Comparative Examples 1 through 4, occurrence of white precipitate was observed to examine whether a high concentration of 5 wt% of minoxidil was dissolved or not, and the formation of transparent gel phase. The results are presented in the following Table 2. [Table 2]
Figure imgf000009_0002
From Table 2, it was identified that the gel composition of Example 1 generated transparent and stable gel phase while completely dissolving a high concentration of 5 wt% of minoxidil. The gel compositions of Comparative Example 1 through 4 failed to dissolve a high concentration of minoxidil and generated white precipitate thus could not be provided as transparent gel phase.
Examples 2 to 6 and Comparative Examples 5 to 10: preparation of gel composition comprising minoxidil (pH control)
With the compositions described in the following Tables 3 and 4, an active ingredient minoxidil and a thickener (Carbopol 940), a pH controller (alkalizer or acidifier), ethanol, purified water and glycerin(concentrated glycerin) were mixed to prepare the gel composition.
The method for mixing ingredients and preparing the gel composition are identical as described in Example 1 and Comparative Examples 1 through 4, except the compositions described in the following Tables 3 and 4. [Table 3]
Figure imgf000010_0001
[Table 4]
Figure imgf000010_0002
Figure imgf000011_0001
After preparing the gel composition of the Examples 2 through 6 and Comparative Examples 5 through 10, the viscosity of each gel composition was measured to identify whether each gel composition has appropriate viscosity and forms as transparent gel phase. The results are presented in the following Tables 5 and 6. [Table 5]
Figure imgf000011_0002
[Table 6]
Figure imgf000011_0003
Figure imgf000012_0001
From the above Tables 5 and 6, it was identified that the gel compositions of Examples 2 through 6 showed appropriate viscosity so as to stay on the applied area such as scalp for a sufficient time, with dissolving a high concentration of 5 wt% of minoxidil, because of its pH controlled to 7.5-9.0, while the gel compositions of Comparative Examples 5 through 10 substantially formed as liquid phase showing too low viscosity, and failed to dissolve a high concentration of minoxidil and could not be provided as transparent and stable gel phase.

Claims

What is claimed is:
1. A gel composition comprising an effective amount of minoxidil, a thickener, and an aqueous solvent containing glycerin.
2. The gel composition according to claim 1, wherein the minoxidil is comprised in an amount of 1 to 10 wt%.
3. The gel composition according to claim 1, wherein the thickener comprises a carbomer thickener.
4. The gel composition according to claim 1, comprising 1 to 10 wt% of the minoxidil, 0.1 to 2 wt% of the thickener, and 89 to 98 wt% of the aqueous solvent containing glycerin.
5. The gel composition according to claim 1, wherein the glycerin is comprised in an amount of 10 to 30 wt% of the total gel composition.
6. The gel composition according to claim 1 , wherein the aqueous solvent comprises glycerin, water and ethanol.
7. The gel composition according to claim 6, wherein the weight ratio of water to ethanol (water : ethanol) is 1 : 2 to 1 : 4.
8. The gel composition according to claim 1, wherein the pH of the composition is 7.5 to 9.0 9. The gel composition according to claim 8, further comprising an amine-based pH controller.
PCT/KR2008/002982 2008-05-06 2008-05-28 Gel composition comprising minoxidil WO2009136677A1 (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013026754A1 (en) * 2011-08-22 2013-02-28 Smiths Heimann Gmbh Liquid mixture used to test and validate test devices
US9091764B2 (en) 2011-08-22 2015-07-28 Smiths Heimann Gmbh Liquid mixture used to test and validate test devices
US9360572B2 (en) 2011-08-22 2016-06-07 Smiths Heimann Gmbh Liquid mixture used to test and validate test devices for inspecting objects or persons
EP2782582A4 (en) * 2011-11-25 2016-09-28 Adrianna Janell Jackson Oil compositions and methods for increasing hair growth and/or preventing hair loss
CN114681403A (en) * 2022-04-02 2022-07-01 山西医科大学 Minoxidil carrier with high drug loading rate and encapsulation rate, gel and preparation thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110548044A (en) * 2019-09-25 2019-12-10 上海理工大学 chitosan minoxidil hair-growing gel and preparation method thereof
CN113057935A (en) * 2021-03-26 2021-07-02 湖南华腾医药有限公司 Minoxidil gel composition and preparation method thereof
CN113599351A (en) * 2021-08-10 2021-11-05 杭州汉库医药科技有限公司 Minoxidil wash-free gel

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5225189A (en) * 1988-02-18 1993-07-06 The Upjohn Company Minoxidil gel
WO2002011698A1 (en) * 2000-08-09 2002-02-14 Pharmacia Ab Novel compositions of minoxidil
KR20040076400A (en) * 2003-02-25 2004-09-01 주식회사 엘지생활건강 Hair care composition containing minoxidal and surfactant cmposite particles
WO2007070069A1 (en) * 2005-12-16 2007-06-21 Celmatrix Corporation Topical administration carrier composition and therapeutic formulations comprising same

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7074747B1 (en) * 1999-07-01 2006-07-11 Johnson & Johnson Consumer Companies, Inc. Cleansing compositions
KR100893469B1 (en) * 2006-12-22 2009-04-17 씨제이제일제당 (주) Compositions containing minoxidil for the hair generation which have an improved skin permeation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5225189A (en) * 1988-02-18 1993-07-06 The Upjohn Company Minoxidil gel
WO2002011698A1 (en) * 2000-08-09 2002-02-14 Pharmacia Ab Novel compositions of minoxidil
KR20040076400A (en) * 2003-02-25 2004-09-01 주식회사 엘지생활건강 Hair care composition containing minoxidal and surfactant cmposite particles
WO2007070069A1 (en) * 2005-12-16 2007-06-21 Celmatrix Corporation Topical administration carrier composition and therapeutic formulations comprising same

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013026754A1 (en) * 2011-08-22 2013-02-28 Smiths Heimann Gmbh Liquid mixture used to test and validate test devices
US9052398B2 (en) 2011-08-22 2015-06-09 Smiths Heimann Gmbh Liquid mixture used to test and validate test devices
US9091764B2 (en) 2011-08-22 2015-07-28 Smiths Heimann Gmbh Liquid mixture used to test and validate test devices
US9360572B2 (en) 2011-08-22 2016-06-07 Smiths Heimann Gmbh Liquid mixture used to test and validate test devices for inspecting objects or persons
EP2782582A4 (en) * 2011-11-25 2016-09-28 Adrianna Janell Jackson Oil compositions and methods for increasing hair growth and/or preventing hair loss
CN114681403A (en) * 2022-04-02 2022-07-01 山西医科大学 Minoxidil carrier with high drug loading rate and encapsulation rate, gel and preparation thereof
CN114681403B (en) * 2022-04-02 2023-08-04 山西医科大学 Minoxidil delivery body with high drug loading and encapsulation efficiency, gel and preparation thereof

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