CN104800149A - External paeonol thermosensitive gel and preparation method thereof - Google Patents
External paeonol thermosensitive gel and preparation method thereof Download PDFInfo
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- CN104800149A CN104800149A CN201510208980.9A CN201510208980A CN104800149A CN 104800149 A CN104800149 A CN 104800149A CN 201510208980 A CN201510208980 A CN 201510208980A CN 104800149 A CN104800149 A CN 104800149A
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Abstract
The invention discloses external paeonol thermosensitive gel and a preparation method thereof. The external paeonol thermosensitive gel comprises the following components in percentage by weight: 0.5-5% of paeonol, 15-30% of poloxamer 407, 1-6% of poloxamer 188, 0.5-5% of a humectant, 0.05-0.3% of an antioxidant, 0.05-0.3% of a metal ion complex agent and 53.4-82.9% of purified water. The external thermosensitive gel for skin is prepared by taking paeonol as a raw material and taking poloxamers as gel matrixes, so that the proceeding of production and preparation processes and the application to the skin are facilitated; a gel-shaped drug-containing layer is formed at the local part of the skin, so that a wound surface can be protected and drug release can be controlled for achieving a treatment effect; moreover, the thermosensitive gel is good in comfort, non-greasy, little in clothes pollution and easy to clean, and the preparation method is simple, low in cost and suitable for large-scale production.
Description
Technical field
The present invention relates to a kind of external preparation for skin paeonol responsive to temperature type gel and preparation method thereof, belong to pharmaceutical technology sectors.
Background technology
Paeonol is extract effective ingredient out in the root bark of ranunculaceae peony or asclepiadaceae plant paniculate swallowwort, and molecular formula is C
9h
10o
3, molecular weight is 166.18.Paeonol be white or the glossiness acicular crystal of micro-yellow, abnormal smells from the patient is special, taste micro-peppery, be soluble in ethanol and methanol, dissolve in the hot water, be insoluble to cold water, fusing point is 49 ~ 51 DEG C.Paeonol has analgesia, antiinflammatory, antipyretic and suppress allergic effect.
Eczema is a kind of allergic skin disease of common easy recurrence, is mainly in women's head-ornaments, extremity bend the position such as side and perineum, are often general or symmetry distribution.Dermatitis is a kind of common skin diseases, refers to that peeling, peeling off appears in skin, thickening, variable color, and the phenomenon such as to itch when touching.The boundary that " eczema " follows " dermatitis " not strict, eczema is the dermatosis of non-infective inflammation in general.Eczema has several feature, and first has the tendency of oozing out, and skin easily flows " water ", just because of easily flowing water so be called eczema visually, " without oozing out " be just dermatitis; Second is pruritus; 3rd is that recurrent exerbation is without stop.Just because of several like this feature, eczema is made to become the dermatosis of chronic, recurrent exerbation, a puzzlement extensive patients.
Since world-renowned biophysicist Toyoichi Tanaka in 1978 finds that gel has volume phase transition phenomenon, gel has attracted the great interest of research worker at once.With going deep into of research, a series of intelligent gel changed by extraneous factor (as temperature, pH value, optical, electrical magnetic field, pressure and ionic strength etc.) stimulation volume, porosity, viscoelasticity, density and refraction index etc. is constantly in the news, and wherein the research of thermosensitive in situ gel is the earliest also the most deeply with extensive.Responsive to temperature type gel is different from ordinary gel, is by temperature controlled intelligent drug-supplying system, and according to the character of the intellectual material selected, it is unique in the character changed mutually between solution and gel to have.Be that liquid form can free-flow when lower temperature, be beneficial to the carrying out of manufacture process; When temperature rises to a certain degree, form semi-solid gel state when namely contacting skin, skin can be close to medicine is played a role.And ordinary gel to be medicine make glop or semi-solid preparation with the adjuvant that can form gel, its Chinese medicine small-particle is dispersed in cancellated liquid, does not have said temperature or other is as the characteristic of the sensitivities such as pH, light, heat.Responsive to temperature type gel is easy to way exhibition, comfort is good, do not hinder the normal physiological effect of skin, and without greasy, little to clothing contamination, easy cleaning, performance is better than ointment.
Paeonol is a kind of effective ingredient of Chinese medicine extraction of Nantural non-toxic, can overcome the shortcoming that the side effect of classical hormonal class drug administration is large.Current external preparation on the market mainly contains paeonol unguentum, Paeonol Gelatum etc., for the treatment of the diseases such as eczema, dermatitis, skin pruritus redness.But be that the external preparation for skin responsive to temperature type gel of raw material then has no relevant report with paeonol.
Summary of the invention
The object of the invention is to make up the deficiencies in the prior art, a kind of external preparation for skin paeonol responsive to temperature type gel and preparation method thereof is provided.The present invention take paeonol as raw material; take poloxamer as gel-type vehicle; make external preparation for skin responsive to temperature type gel; not only be beneficial to the carrying out of manufacture process; also be beneficial to and be applied on skin; form gel medicated layer at local skin, not only can protect wound surface but also therapeutical effect can be played by Drug controlled release, and this responsive to temperature type gel comfort is good, without greasy, little to clothing contamination, easy cleaning.
The technical scheme that the present invention solves the problems of the technologies described above is as follows: a kind of external preparation for skin paeonol responsive to temperature type gel, is made up of the component of following percetage by weight: the paeonol of 0.5 ~ 5%, the poloxamer188 of 15 ~ 30%, 1 ~ 6% PLURONICS F87,0.5 ~ 5% wetting agent, 0.05 ~ 0.3% antioxidant, the complexing of metal ion agent of 0.05 ~ 0.3%, the purified water of 53.4 ~ 82.9%.
The function of several component of the present invention is respectively:
Paeonol is a kind of effective ingredient of Chinese medicine extraction of Nantural non-toxic, can overcome the shortcoming that the side effect of classical hormonal class drug administration is large.Paeonol is as the principal agent of external preparation for skin paeonol responsive to temperature type gel of the present invention.
Poloxamer (Poloxamer) is polyoxyethylene poly-oxygen propylene aether block copolymer, and commodity are called pluronic (Pluronic), is the novel macromolecule non-ionic surface active agent of a class.Poloxamer is without physiologically active, and without hemolytic, to no skin irritation, toxicity is little.Poloxamer188, when concentration is 15 ~ 25%, be liquid when there is room temperature, temperature convert the reverse hot gel characteristic of gel to when raising, while convenient application also can prolong drug at the residence time of medicine-feeding part, be conducive to improving bioavailability and curative effect.PLURONICS F87, when concentration is 20 ~ 30%, form gel, this gel has temperature sensitivity, and heating or cooling can make gel that reversible change occurs, but do not affect the character of gel.It is liquid that the poloxamer of single model is difficult to reach when room temperature, and converting gel state to close to during skin surface temperature, therefore, the present invention adopts the poloxamer188 of variable concentrations and PLURONICS F87 to carry out proportioning, to reach desirable effect.The mixture of poloxamer188 and PLURONICS F87, as the water-soluble base of external preparation for skin paeonol responsive to temperature type gel of the present invention.
Wetting agent is the hygroscopic compound that a class can absorb moisture from malaria, by absorbing and keeping moisture to reach moistening effect.
Antioxidant is the material that a class can effectively stop or delay autoxidation, is the important component part of excipient substance, is mainly used in the oxidation deterioration preventing medicine and preparation thereof, and be oxidized cause variable color, produce precipitation and otherwise unstability.
Metal chelating agent refers to and can be combined the organic compound forming stable comple with many kinds of metal ions.Desirable chelating agent should be nontoxic or low toxicity, can form stable water soluble complex with complexing of metal ion, avoids trace metal ion in preparation to the catalytic action of medicine, to ensure medicine stability in the formulation.
On the basis of technique scheme, the present invention can also do following improvement.
Further, be made up of the component of following percetage by weight: the paeonol of 1%, the poloxamer188 of 23%, 2% PLURONICS F87,1% wetting agent, 0.2% antioxidant, the complexing of metal ion agent of 0.1%, the purified water of 72.7%.
Further, purity >=98% of described paeonol mass fraction, described wetting agent is glycerol, and described antioxidant is sodium sulfite, and described complexing of metal ion agent is EDTA-2Na.
A preparation method for external preparation for skin paeonol responsive to temperature type gel, comprises the steps:
(1) gel-type vehicle is prepared: getting percetage by weight is the poloxamer188 of 15 ~ 30% and the PLURONICS F87 of 1 ~ 6%, being scattered in percetage by weight is in the purified water of 53.4 ~ 82.9%, then in 4 DEG C of placement >=12h, obtain Poloxamer solution, by percetage by weight be again 0.5 ~ 5% wetting agent slowly add in above-mentioned Poloxamer solution, limit edged stirs, obtain solution A, get again percetage by weight be 0.05 ~ 0.3% antioxidant slowly add in above-mentioned solution A, limit edged stirs, obtain solution B, get again percetage by weight be 0.05 ~ 0.3% complexing of metal ion agent slowly add in above-mentioned solution B, limit edged stirs, obtain gel-type vehicle,
(2) preparation of paeonol responsive to temperature type gel: get the paeonol that percetage by weight is 0.5 ~ 5%, adds step (1) gained gel-type vehicle, stirs, and obtains paeonol responsive to temperature type gel.
On the basis of technique scheme, the present invention can also do following improvement.
Further, the percetage by weight of step (1) described poloxamer188 is 23%, the percetage by weight of described PLURONICS F87 is 2%, the percetage by weight of described purified water is 72.7%, the percetage by weight of described wetting agent is 1%, the percetage by weight of described antioxidant is 0.2%, and the percetage by weight of described complexing of metal ion agent is 0.1%.
Further, described wetting agent is glycerol, and described antioxidant is sodium sulfite, and described complexing of metal ion agent is EDTA-2Na.
Further, the percetage by weight of step (2) described paeonol is 1%, purity >=98% of described paeonol mass fraction.
The invention has the beneficial effects as follows:
(1) the present invention take paeonol as raw material; take poloxamer as gel-type vehicle; make external preparation for skin responsive to temperature type gel; not only be beneficial to the carrying out of manufacture process; also be beneficial to and be applied on skin; form gel medicated layer at local skin, not only can protect wound surface but also therapeutical effect can be played by Drug controlled release.
(2) external preparation for skin responsive to temperature type gel comfort of the present invention good, without greasy, little to clothing contamination, easy cleaning.
(3) preparation method of the present invention is simple, cost is low, be applicable to large-scale production.
Detailed description of the invention
Be described principle of the present invention and feature below in conjunction with specific embodiment, example, only for explaining the present invention, is not intended to limit scope of the present invention.
Embodiment 1:
(1) gel-type vehicle is prepared: get the poloxamer188 of 15g and the PLURONICS F87 of 6g, be scattered in the purified water of 73.15g, then 12h is placed in 4 DEG C, obtain Poloxamer solution, again the glycerol of 0.5g is slowly added in above-mentioned Poloxamer solution, limit edged stirs, obtain solution A, the sodium sulfite getting 0.3g more slowly adds in above-mentioned solution A, limit edged stirs, and obtain solution B, then the EDTA-2Na getting 0.05g slowly adds in above-mentioned solution B, limit edged stirs, and obtains gel-type vehicle;
(2) preparation of paeonol responsive to temperature type gel: the paeonol getting 5g, purity >=98% of described paeonol mass fraction, adds step (1) gained gel-type vehicle, stirs, and obtains paeonol responsive to temperature type gel.
Embodiment 2:
(1) prepare gel-type vehicle: get the poloxamer188 of 23g and the PLURONICS F87 of 2g, be scattered in the purified water of 72.7g, then place 14h in 4 DEG C, obtain Poloxamer solution, slowly add in above-mentioned Poloxamer solution by the glycerol of 1g again, limit edged stirs, and obtains solution A, the sodium sulfite getting 0.2g more slowly adds in above-mentioned solution A, limit edged stirs, and obtain solution B, then the EDTA-2Na getting 0.1g slowly adds in above-mentioned solution B, limit edged stirs, and obtains gel-type vehicle;
(2) preparation of paeonol responsive to temperature type gel: the paeonol getting 1g, purity >=98% of described paeonol mass fraction, adds step (1) gained gel-type vehicle, stirs, and obtains paeonol responsive to temperature type gel.
Embodiment 3:
(1) gel-type vehicle is prepared: get the poloxamer188 of 30g and the PLURONICS F87 of 1g, be scattered in the purified water of 63.15g, then 16h is placed in 4 DEG C, obtain Poloxamer solution, again the glycerol of 5g is slowly added in above-mentioned Poloxamer solution, limit edged stirs, obtain solution A, the sodium sulfite getting 0.05g more slowly adds in above-mentioned solution A, limit edged stirs, and obtain solution B, then the EDTA-2Na getting 0.3g slowly adds in above-mentioned solution B, limit edged stirs, and obtains gel-type vehicle;
(2) preparation of paeonol responsive to temperature type gel: the paeonol getting 0.5g, purity >=98% of described paeonol mass fraction, adds step (1) gained gel-type vehicle, stirs, and obtains paeonol responsive to temperature type gel.
Embodiment 4:
(1) gel-type vehicle is prepared: get the poloxamer188 of 15g and the PLURONICS F87 of 1g, be scattered in the purified water of 82.9g, then 18h is placed in 4 DEG C, obtain Poloxamer solution, again the glycerol of 0.5g is slowly added in above-mentioned Poloxamer solution, limit edged stirs, obtain solution A, the sodium sulfite getting 0.05g more slowly adds in above-mentioned solution A, limit edged stirs, and obtain solution B, then the EDTA-2Na getting 0.05g slowly adds in above-mentioned solution B, limit edged stirs, and obtains gel-type vehicle;
(2) preparation of paeonol responsive to temperature type gel: the paeonol getting 0.5g, purity >=98% of described paeonol mass fraction, adds step (1) gained gel-type vehicle, stirs, and obtains paeonol responsive to temperature type gel.
Embodiment 5:
(1) prepare gel-type vehicle: get the poloxamer188 of 30g and the PLURONICS F87 of 6g, be scattered in the purified water of 53.4g, then place 20h in 4 DEG C, obtain Poloxamer solution, slowly add in above-mentioned Poloxamer solution by the glycerol of 5g again, limit edged stirs, and obtains solution A, the sodium sulfite getting 0.3g more slowly adds in above-mentioned solution A, limit edged stirs, and obtain solution B, then the EDTA-2Na getting 0.3g slowly adds in above-mentioned solution B, limit edged stirs, and obtains gel-type vehicle;
(2) preparation of paeonol responsive to temperature type gel: the paeonol getting 5g, purity >=98% of described paeonol mass fraction, adds step (1) gained gel-type vehicle, stirs, and obtains paeonol responsive to temperature type gel.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (7)
1. an external preparation for skin paeonol responsive to temperature type gel, it is characterized in that, be made up of the component of following percetage by weight: the paeonol of 0.5 ~ 5%, the poloxamer188 of 15 ~ 30%, 1 ~ 6% PLURONICS F87,0.5 ~ 5% wetting agent, 0.05 ~ 0.3% antioxidant, the complexing of metal ion agent of 0.05 ~ 0.3%, the purified water of 53.4 ~ 82.9%.
2. a kind of external preparation for skin paeonol responsive to temperature type gel according to claim 1, it is characterized in that, be made up of the component of following percetage by weight: the paeonol of 1%, the poloxamer188 of 23%, 2% PLURONICS F87,1% wetting agent, 0.2% antioxidant, the complexing of metal ion agent of 0.1%, the purified water of 72.7%.
3. a kind of external preparation for skin paeonol responsive to temperature type gel according to claim 1 and 2, it is characterized in that, purity >=98% of described paeonol mass fraction, described wetting agent is glycerol, described antioxidant is sodium sulfite, and described complexing of metal ion agent is EDTA-2Na.
4. a preparation method for external preparation for skin paeonol responsive to temperature type gel, is characterized in that, comprise the steps:
(1) gel-type vehicle is prepared: getting percetage by weight is the poloxamer188 of 15 ~ 30% and the PLURONICS F87 of 1 ~ 6%, being scattered in percetage by weight is in the purified water of 53.4 ~ 82.9%, then in 4 DEG C of placement >=12h, obtain Poloxamer solution, by percetage by weight be again 0.5 ~ 5% wetting agent slowly add in above-mentioned Poloxamer solution, limit edged stirs, obtain solution A, get again percetage by weight be 0.05 ~ 0.3% antioxidant slowly add in above-mentioned solution A, limit edged stirs, obtain solution B, get again percetage by weight be 0.05 ~ 0.3% complexing of metal ion agent slowly add in above-mentioned solution B, limit edged stirs, obtain gel-type vehicle,
(2) preparation of paeonol responsive to temperature type gel: get the paeonol that percetage by weight is 0.5 ~ 5%, adds step (1) gained gel-type vehicle, stirs, and obtains paeonol responsive to temperature type gel.
5. the preparation method of a kind of external preparation for skin paeonol responsive to temperature type gel according to claim 4, it is characterized in that, the percetage by weight of step (1) described poloxamer188 is 23%, the percetage by weight of described PLURONICS F87 is 2%, the percetage by weight of described purified water is 72.7%, the percetage by weight of described wetting agent is 1%, and the percetage by weight of described antioxidant is 0.2%, and the percetage by weight of described complexing of metal ion agent is 0.1%.
6. the preparation method of a kind of external preparation for skin paeonol responsive to temperature type gel according to claim 4 or 5, it is characterized in that, described wetting agent is glycerol, and described antioxidant is sodium sulfite, and described complexing of metal ion agent is EDTA-2Na.
7. the preparation method of a kind of external preparation for skin paeonol responsive to temperature type gel according to claim 4, it is characterized in that, the percetage by weight of step (2) described paeonol is 1%, purity >=98% of described paeonol mass fraction.
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| CN109568262A (en) * | 2019-01-04 | 2019-04-05 | 华南农业大学 | A kind of Doxycycline Temperature-sensitive in situ gel uterus perfusion and preparation method thereof for sow |
| CN109846816A (en) * | 2019-03-06 | 2019-06-07 | 西安交通大学 | A kind of alkannin temperature-sensitive hydrogel and its preparation method and application |
| CN111297796A (en) * | 2018-12-12 | 2020-06-19 | 广州汇君科技有限公司 | Paeonol gel |
| CN112546092A (en) * | 2020-12-09 | 2021-03-26 | 蓝佳堂生物医药（福建）有限公司 | Compound gel for treating mosquito bites and preparation method thereof |
| CN113546015A (en) * | 2021-07-26 | 2021-10-26 | 天津市海尔斯科技有限公司 | Honeycomb hydrogel based on citrus fruit extract and preparation process thereof |
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| CN101455654A (en) * | 2007-12-13 | 2009-06-17 | 天津医科大学 | Arginine ibuprofen gel and preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111297796A (en) * | 2018-12-12 | 2020-06-19 | 广州汇君科技有限公司 | Paeonol gel |
| CN109568262A (en) * | 2019-01-04 | 2019-04-05 | 华南农业大学 | A kind of Doxycycline Temperature-sensitive in situ gel uterus perfusion and preparation method thereof for sow |
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Application publication date: 20150729 |