Minoxidil external preparation composition as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a minoxidil external preparation composition as well as a preparation method and application thereof. The invention provides a minoxidil external preparation composition. The minoxidil external preparation composition comprises minoxidil, finasteride, pharmaceutic adjuvants, organic acid, ethanol and water. By adding finasteride and pharmaceutic adjuvants, the treatment effect on alopecia is enhanced; by adding a proper amount of organic acid, the dissolution of minoxidil can be promoted in the absence of propylene glycol, so that the problem of replacing a propylene glycol solvent is solved. The minoxidil external composition prepared by the invention is stable, the treatment effect of the minoxidil external composition on alopecia is obviously higher than that of a solution only containing a minoxidil single component, and the minoxidil external composition does not contain a propylene glycol component, so that the occurrence of propylene glycol allergy is avoided. And the preparation method is simple, stable and good in reproducibility.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a minoxidil external-use composition and a preparation method and application thereof. Background Art

[0002] Minoxidil, with the chemical name 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, was first used clinically as a drug for the treatment of hypertension. Later, it was found to promote hair growth and was approved by the FDA for marketing in 1988. Its indications are the treatment of seborrheic alopecia and alopecia areata, and its dosage form is a topical solution.

[0003] Minoxidil is currently the only external chemical drug in the world that has a significant therapeutic effect on hair loss. It can promote hair growth through multiple pathways, is effective and safe, and therefore is widely promoted in clinical practice.

[0004] Traditional hair growth preparations use propylene glycol as a solvent, which can cause allergic reactions in some people. The current sensitization mechanism is mainly propylene glycol irritation allergy. However, propylene glycol has a solubility-promoting effect on minoxidil, and the solubility of minoxidil in solvents lacking propylene glycol is low.

[0005] Therefore, there is an urgent need for a minoxidil hair growth preparation that does not contain propylene glycol and also has a good hair growth effect. Summary of the invention

[0006] The object of the present invention is to provide a minoxidil topical composition and a preparation method and application thereof. The minoxidil topical composition provided by the present invention does not contain propylene glycol and also has a good hair growth effect.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] The invention provides a minoxidil external preparation composition, comprising minoxidil, finasteride, pharmaceutical excipients, organic acid, ethanol and water.

[0009] Preferably, in terms of mass percentage, the minoxidil topical composition comprises 2-15% minoxidil, 0.005-0.1% finasteride, 0.005-0.1% pharmaceutical excipients, 0.1-5% organic acid, 25-60% ethanol and the balance water.

[0010] Preferably, the minoxidil topical composition comprises 2-10% minoxidil, 0.01-0.08% finasteride, 0.01-0.08% pharmaceutical excipients, 0.5-5% organic acid, 40-60% ethanol and the balance water.

[0011] Preferably, the organic acid comprises one or more of citric acid, lactic acid, azelaic acid, salicylic acid, mandelic acid, acetic acid and malic acid.

[0012] Preferably, the pharmaceutical excipients include one or more of vitamin A, vitamin E, vitamin B5, vitamin B7, vitamin H, caffeine, biotin tripeptide-1, cyclodextrin, glycerol, lysine, threonine, glutamic acid, tripeptide-1, acetyl tetrapeptide-3, tripeptide-1 copper, lecithin, cholesterol and disodium edetate.

[0013] Preferably, the water is pure water.

[0014] The present invention also provides a method for preparing the minoxidil external-use composition described in the above technical solution, comprising the following steps:

[0015] Minoxidil, finasteride, pharmaceutical excipients, organic acid, ethanol and water are mixed to obtain the minoxidil external preparation composition.

[0016] Preferably, the mixing comprises:

[0017] uniformly mixing the organic acid, ethanol and part of water to obtain a mixed solvent;

[0018] Minoxidil, finasteride and pharmaceutical excipients are added to the mixed solvent, stirred and then the remaining water is added to obtain the minoxidil topical composition.

[0019] Preferably, the stirring time is 2 hours.

[0020] The present invention also provides the use of the minoxidil topical composition described in the above technical solution or the minoxidil topical composition prepared by the preparation method described in the above technical solution as a hair growth preparation.

[0021] The present invention provides a minoxidil topical composition, comprising minoxidil, finasteride, pharmaceutical excipients, organic acid, ethanol and water. The present invention enhances the therapeutic effect on hair loss by adding finasteride and pharmaceutical excipients; by adding a suitable organic acid, the dissolution of minoxidil can be promoted in the absence of propylene glycol, thereby solving the problem of replacing the propylene glycol solvent. The minoxidil topical composition prepared by the present invention is stable, and the therapeutic effect on hair loss is significantly higher than that of a solution containing only a single component of minoxidil, and there is no propylene glycol component, thereby avoiding the occurrence of propylene glycol allergy. The preparation method is simple, stable and reproducible. DETAILED DESCRIPTION

[0022] The invention provides a minoxidil external preparation composition, comprising minoxidil, finasteride, pharmaceutical excipients, organic acid, ethanol and water.

[0023] In terms of mass percentage, the minoxidil topical composition provided by the present invention comprises 2-15% minoxidil, more preferably 2-10%.

[0024] In terms of mass percentage, the minoxidil topical composition provided by the present invention comprises 0.005-0.1% finasteride, and more preferably 0.01-0.08%.

[0025] In terms of mass percentage, the minoxidil topical composition provided by the present invention comprises 0.005-0.1% of pharmaceutical excipients, and more preferably 0.01-0.08%. In the present invention, the pharmaceutical excipients preferably include one or more of vitamin A, vitamin E, vitamin B5, vitamin B7, vitamin H, caffeine, biotin tripeptide-1, cyclodextrin, glycerol, lysine, threonine, glutamic acid, tripeptide-1, acetyl tetrapeptide-3, tripeptide-1 copper, lecithin, cholesterol and disodium edetate.

[0026] In terms of mass percentage, the minoxidil topical preparation composition provided by the present invention comprises 0.1-5% of organic acid, more preferably 0.5-5%. In the present invention, the organic acid preferably comprises one or more of citric acid, lactic acid, azelaic acid, salicylic acid, mandelic acid, acetic acid and malic acid.

[0027] In terms of mass percentage, the minoxidil external preparation composition provided by the present invention comprises 25 to 60% ethanol, more preferably 40 to 60%.

[0028] In terms of mass percentage, the minoxidil topical preparation composition provided by the present invention includes the balance of water. In the present invention, the water is preferably pure water.

[0029] The present invention also provides a method for preparing the minoxidil external-use composition described in the above technical solution, comprising the following steps:

[0030] Minoxidil, finasteride, pharmaceutical excipients, organic acid, ethanol and water are mixed to obtain the minoxidil external preparation composition.

[0031] In the present invention, the mixing preferably includes:

[0032] uniformly mixing the organic acid, ethanol and part of water to obtain a mixed solvent;

[0033] Minoxidil, finasteride and pharmaceutical excipients are added to the mixed solvent, stirred and then the remaining water is added to obtain the minoxidil topical composition.

[0034] The present invention has no special limitation on the ratio of the partial water to the remaining water, as long as the water is added stepwise and the remaining water is used to make a constant volume.

[0035] In the present invention, the stirring time is preferably 2 hours.

[0036] The present invention also provides the use of the minoxidil topical composition described in the above technical solution or the minoxidil topical composition prepared by the preparation method described in the above technical solution as a hair growth preparation.

[0037] Unless otherwise specified, the materials and equipment used in the present invention are all commercially available products in the art.

[0038] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0039] Example 1

[0040] Take 500 mL of ethanol, 400 mL of pure water and 10 g of lactic acid and mix them thoroughly to obtain a mixed solvent;

[0041] 50 g of minoxidil, 0.1 g of finasteride, 0.1 g of caffeine and 0.05 g of vitamin A were added to the mixed solvent, stirred for 2 hours until completely dissolved, and finally pure water was added to make the volume to 1 L to obtain a minoxidil topical composition.

[0042] Example 2

[0043] Take 500 mL of ethanol, 400 mL of pure water and 10 g of lactic acid and mix them thoroughly to obtain a mixed solvent;

[0044] 50 g of minoxidil, 0.1 g of finasteride, 0.2 g of caffeine, 0.05 g of vitamin A and 0.2 g of biotin tripeptide-1 were added to the mixed solvent, stirred for 2 hours until completely dissolved, and finally pure water was added to make the volume to 1 L to obtain a minoxidil topical composition.

[0045] Comparative Example 1

[0046] Take 500 mL of ethanol and 400 mL of propylene glycol, mix them evenly, add 50 g of minoxidil, and finally add pure water to make the volume to 1 L to obtain a minoxidil topical composition.

[0047] Performance Testing

[0048] The minoxidil topical preparation compositions obtained in Examples 1 to 2 and Comparative Example 1 were used in a mouse hair growth experiment, with pure water as a blank control group. The results are shown in Table 1;

[0049] Table 1 Results of the mouse hair growth experiment of the minoxidil topical preparations of the embodiments and comparative examples

[0050] Experimental batch number Dosage (mL / piece) Average gross weight (mg) Average hair length (mm) Blank control group 0.4 9.12±3.16 1.60±0.51 Comparative Example 1 0.4 12.04±3.97* 1.92±0.87 Example 1 0.4 13.99±3.72** 2.05±0.72* Example 2 0.4 14.37±4.27** 2.35±0.67**

[0051] The above experimental test results show that in terms of hair growth effect, the external use composition of the present invention is significantly better than that of comparative example 1, so the present invention can effectively enhance the effect of treating hair loss.

[0052] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A minoxidil external-use composition, characterized in that: Includes minoxidil, finasteride, pharmaceutical excipients, organic acids, ethanol and water.

2. The minoxidil external-use composition according to claim 1, characterized in that Calculated by mass percentage, the minoxidil topical composition comprises 2-15% minoxidil, 0.005-0.1% finasteride, 0.005-0.1% pharmaceutical excipients, 0.1-5% organic acid, 25-60% ethanol and the balance water.

3. The minoxidil external-use composition according to claim 2, characterized in that: The minoxidil external preparation composition comprises 2-10% minoxidil, 0.01-0.08% finasteride, 0.01-0.08% pharmaceutical excipients, 0.5-5% organic acid, 40-60% ethanol and the balance water.

4. The minoxidil external-use composition according to any one of claims 1 to 3, characterized in that: The organic acid includes one or more of citric acid, lactic acid, azelaic acid, salicylic acid, mandelic acid, acetic acid and malic acid.

5. The minoxidil external-use composition according to any one of claims 1 to 3, characterized in that: The pharmaceutical excipients include one or more of vitamin A, vitamin E, vitamin B5, vitamin B7, vitamin H, caffeine, biotin tripeptide-1, cyclodextrin, glycerol, lysine, threonine, glutamic acid, tripeptide-1, acetyl tetrapeptide-3, tripeptide-1 copper, lecithin, cholesterol and disodium edetate.

6. The minoxidil external-use composition according to any one of claims 1 to 3, characterized in that: The water is pure water.

7. The method for preparing the minoxidil external preparation composition according to any one of claims 1 to 6, characterized in that: The following steps are involved: Minoxidil, finasteride, pharmaceutical excipients, organic acid, ethanol and water are mixed to obtain the minoxidil external preparation composition.

8. The preparation method according to claim 7, characterized in that: The mixing includes: uniformly mixing the organic acid, ethanol and part of water to obtain a mixed solvent; Minoxidil, finasteride and pharmaceutical excipients are added to the mixed solvent, stirred and then the remaining water is added to obtain the minoxidil topical composition.

9. The preparation method according to claim 8, characterized in that: The stirring time is 2h.

10. Use of the minoxidil external preparation composition according to any one of claims 1 to 6 or the minoxidil external preparation composition prepared by the preparation method according to any one of claims 7 to 9 as a hair growth preparation.