CN105708842B - A topical pharmaceutical composition - Google Patents
A topical pharmaceutical composition Download PDFInfo
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- CN105708842B CN105708842B CN201410723179.3A CN201410723179A CN105708842B CN 105708842 B CN105708842 B CN 105708842B CN 201410723179 A CN201410723179 A CN 201410723179A CN 105708842 B CN105708842 B CN 105708842B
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Abstract
The invention belongs to the technical field of medicines, and mainly relates to an external pharmaceutical composition, wherein the external pharmaceutical composition contains 0.05g of calcipotriol (anhydride), 0.643g of betamethasone dipropionate, 30-75g of medium-chain triglyceride, 20-60g of liquid paraffin and 0.01-0.1g of racemization α -tocopherol.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a more stable external pharmaceutical composition.
Background
Calcipotriol is a VD3 derivative, and in vitro data show that calcipotriol can induce differentiation and inhibit keratinocyte proliferation, which is the basis for treating psoriasis. Betamethasone dipropionate belongs to a high-efficiency halogen-containing corticosteroid medicament, is similar to other local-acting corticosteroids, and has the characteristics of anti-inflammation, itching relieving, vasoconstriction and immunosuppression. Both are first-line external psoriasis treatment medicines. Authoritative clinical data show that the effective rate of the compound preparation of the calcipotriol and the betamethasone dipropionate for treating the psoriasis is obviously superior to the effective rate of the compound preparation of the calcipotriol and the betamethasone dipropionate when the calcipotriol and the betamethasone dipropionate are used independently.
Calcipotriol betamethasone ointment researched and developed by Ireland rio pharmaceutical Co., Ltd (LEO Pharma Inc.) is marketed in the United states in 1 month of 2006 under the trade name of
And then approved to be marketed in 9 months in 2008 under the name of
LEO patent ZL00807667.7 discloses the dissolution of calcipotriol in solvent C, represented by polyoxypropylene-15-S-stearyl ether, and patenting of the polyoxypropylene-15-S-stearyl ether. Research shows that when the polyoxypropylene-15-S-stearyl alcohol ether is used as a solvent, the following problems exist in the preparation process: because hydrocarbon substances such as ether and vaseline are not mutually soluble, a phase separation phenomenon occurs, and the ointment is unstable, increases impurities and has uneven content when stored for a long time at high temperature.
In view of the above-mentioned drawbacks of patent ZL00807667.7, patent application CN201310030616.9 provides a calcipotriol betamethasone ointment in which calcipotriol and betamethasone dipropionate are present in the form of micropowder particles uniformly dispersed in caprylic/capric polyethylene glycol glyceride. The ointment has good stability at high temperature above 40 deg.C, and no phase separation even at 50 deg.C.
Disclosure of Invention
It is an object of the present invention to provide a pharmaceutical composition for external use comprising calcipotriol and betamethasone dipropionate, which is more stable than the prior art.
The above object of the present invention is achieved by the following technical solutions:
a pharmaceutical composition for external use, which comprises the following raw materials per 1000g of the pharmaceutical composition:
the pharmaceutical composition may further comprise a pharmaceutically acceptable antioxidant, wherein the antioxidant is selected from one or more of vitamin E, vitamin C, butylated hydroxytoluene and citric acid.
The pharmaceutical composition may further comprise a pharmaceutically acceptable penetration enhancer, wherein the penetration enhancer is one or more selected from oleyl alcohol, linoleyl alcohol, linolenyl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol and stearyl alcohol.
The pharmaceutical composition may further comprise pharmaceutically acceptable ointment base, wherein the ointment base is selected from one or more of white vaseline, liquid paraffin, lanolin, beeswax, and spermaceti wax.
In one embodiment of the invention, per 1000g of the pharmaceutical composition:
in another embodiment of the invention, per 1000g of the pharmaceutical composition comprises:
in a preferred embodiment of the invention, per 1000g of the pharmaceutical composition:
in another preferred embodiment of the invention, per 1000g of the pharmaceutical composition:
in another preferred embodiment of the invention, per 1000g of the pharmaceutical composition:
in another preferred embodiment of the invention, per 1000g of the pharmaceutical composition:
another object of the present invention is to provide a method for preparing the above pharmaceutical composition.
The preparation method of the pharmaceutical composition provided by the invention comprises the following steps:
(1) weighing ointment matrix according to the formula amount, heating in water bath at 60 deg.C until completely melting, cooling to 45-50 deg.C, adding antioxidant and/or penetration enhancer if antioxidant and/or penetration enhancer exists in the formula, and stirring well for use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Detailed Description
The present invention is described in further detail with reference to specific examples and test examples, but the scope of the present invention should not be construed as being limited thereto.
Example 1
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline with the formula amount, heating in a water bath at 60 ℃ until the white vaseline is completely melted, and cooling to 45-50 ℃ for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Example 2
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline with the formula amount, heating in a water bath at 60 ℃ until the white vaseline is completely melted, and cooling to 45-50 ℃ for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Example 3
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline with the formula amount, heating in a water bath at 60 ℃ until the white vaseline is completely melted, and cooling to 45-50 ℃ for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Example 4
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline with the amount of the prescription, heating the white vaseline in a water bath at 60 ℃ until the white vaseline is completely melted, cooling the mixture to 45-50 ℃, adding butylated hydroxytoluene with the amount of the prescription, and uniformly stirring the mixture for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Example 5
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline with the amount of the prescription, heating the white vaseline in a water bath at 60 ℃ until the white vaseline is completely melted, cooling the mixture to 45-50 ℃, adding butylated hydroxytoluene with the amount of the prescription, and uniformly stirring the mixture for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Example 6
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline with the formula amount, heating the white vaseline in a water bath at 60 ℃ until the white vaseline is completely melted, cooling the mixture to 45-50 ℃, adding butylated hydroxytoluene and oleyl alcohol with the formula amount, and uniformly stirring the mixture for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Example 7
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline and lanolin in the prescribed amount, heating and mixing in a water bath at 60 ℃ until the white vaseline and the lanolin are completely melted, cooling to 45-50 ℃, adding butylated hydroxytoluene, and uniformly stirring for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Example 8
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline and lanolin in the prescribed amount, heating and mixing in a water bath at 60 ℃ until the white vaseline and the lanolin are completely melted, cooling to 45-50 ℃, adding butylated hydroxytoluene, and uniformly stirring for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Example 9
Prescription:
the preparation process comprises the following steps:
(1) weighing white vaseline with the formula amount, heating in a water bath at 60 ℃ until the white vaseline is completely melted, and cooling to 45-50 ℃ for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription (the particle size of 90 percent is less than 15 mu m), and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging.
Test example 1 stability examination
Samples from examples 1-9 were taken and a commercially available calcipotriol betamethasone ointment (trade name:
) The sample was left at 50 ℃ for 4 weeks, and the properties, coatability, particle size and related substances were examined by sampling at 2 nd and 4 th weeks, respectively. The results are shown in Table 1.
As can be seen from the data in Table 1, the pharmaceutical composition of the present invention has better stability at a high temperature of 50 ℃, which indicates that the pharmaceutical composition of the present invention has better quality and higher safety.
Table 1 stability test results
Claims (1)
1. A pharmaceutical composition for external use, which is formulated as follows:
the granularity of 90% betamethasone dipropionate particles is less than 15 mu m;
the external pharmaceutical composition is prepared by the following steps:
(1) weighing white vaseline with the formula amount, heating in a water bath at 60 ℃ until the white vaseline is completely melted, and cooling to 45-50 ℃ for later use;
(2) weighing liquid paraffin with the amount of the prescription, adding racemization α -tocopherol with the amount of the prescription, stirring until the mixture is completely dissolved, adding betamethasone dipropionate with the amount of the prescription, and stirring until the mixture is uniformly dispersed for later use;
(3) weighing medium-chain triglyceride according to the prescription amount, adding calcipotriol according to the prescription amount, and heating in a water bath at 50 ℃ until the medium-chain triglyceride is completely dissolved for later use;
(4) adding the products of the steps (2) and (3) into the product of the step (1), and emulsifying for 15min at the speed of 4000 rpm;
(5) cooling to 25-35 deg.C after emulsification, and packaging;
the total impurity content of calcipotriol related substances in the external pharmaceutical composition is 1.32%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410723179.3A CN105708842B (en) | 2014-12-03 | 2014-12-03 | A topical pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410723179.3A CN105708842B (en) | 2014-12-03 | 2014-12-03 | A topical pharmaceutical composition |
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| Publication Number | Publication Date |
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| CN105708842A CN105708842A (en) | 2016-06-29 |
| CN105708842B true CN105708842B (en) | 2020-06-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201410723179.3A Active CN105708842B (en) | 2014-12-03 | 2014-12-03 | A topical pharmaceutical composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108815174A (en) * | 2018-05-25 | 2018-11-16 | 昆山普瑞凯纳米技术有限公司 | A kind of modified form fat-soluble compositions and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101730522A (en) * | 2007-07-09 | 2010-06-09 | 茵坦蒂斯股份有限公司 | Pharmaceutical composition for topical application of poorly soluble compounds |
| CN102939078A (en) * | 2010-06-11 | 2013-02-20 | 利奥制药有限公司 | A pharmaceutical spray composition comprising a vitamin d analogue and a corticosteroid |
| CN103110648A (en) * | 2013-01-25 | 2013-05-22 | 江苏圣宝罗药业有限公司 | Calcipotriol betamethasone ointment and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070189977A1 (en) * | 2004-06-07 | 2007-08-16 | Jie Zhang | Spray-on formulations and methods for dermal delivery of drugs |
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- 2014-12-03 CN CN201410723179.3A patent/CN105708842B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101730522A (en) * | 2007-07-09 | 2010-06-09 | 茵坦蒂斯股份有限公司 | Pharmaceutical composition for topical application of poorly soluble compounds |
| CN102939078A (en) * | 2010-06-11 | 2013-02-20 | 利奥制药有限公司 | A pharmaceutical spray composition comprising a vitamin d analogue and a corticosteroid |
| CN103110648A (en) * | 2013-01-25 | 2013-05-22 | 江苏圣宝罗药业有限公司 | Calcipotriol betamethasone ointment and preparation method thereof |
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| CN105708842A (en) | 2016-06-29 |
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