LU500473B1 - Temperature Sensitive Gel of Curcumin Clathrate and Preparation Method and Application Thereof - Google Patents

Temperature Sensitive Gel of Curcumin Clathrate and Preparation Method and Application Thereof Download PDF

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LU500473B1
LU500473B1 LU500473A LU500473A LU500473B1 LU 500473 B1 LU500473 B1 LU 500473B1 LU 500473 A LU500473 A LU 500473A LU 500473 A LU500473 A LU 500473A LU 500473 B1 LU500473 B1 LU 500473B1
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curcumin
clathrate
von
einschlussverbindung
gel
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Yuanwei Liang
Ying Liu
Jianping Chen
Xiaoming Qin
Saiyi Zhong
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Univ Guangdong Ocean
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Abstract

The invention discloses a curcumin clathrate temperature sensitive gel and a preparation method as well as application thereof, belonging to the technical field of pharmacy. The mass concentration of curcumin clathrate in the curcumin clathrate temperature sensitive gel is 1%-5%, and the curcumin clathrate comprises curcumin, d-borneol and Beta-cyclodextrin. According to the invention, curcumin clathrate is used as an additive and temperature-sensitive gel is used as a carrier to prepare curcumin temperature-sensitive gel, and the synergistic effect of components in the curcumin temperature-sensitive gel has obvious effect on skin wounds, especially burns and scalds. The invention improves the bioavailability of curcumin and provides a direction for treating skin burns and scalds; The gel provided by the invention improves the bioavailability of curcumin while the preparation method is simple and feasible, which has no toxic and side effects, and can be widely used for treating skin wounds.

Description

DESCRIPTION Temperature Sensitive Gel of Curcumin Clathrate and Preparation Method and Application Thereof
TECHNICAL FIELD The invention relates to the technical field of pharmacy, in particular to a curcumin clathrate temperature sensitive gel and a preparation method and application thereof.
BACKGROUND Curcumin is a chemical component extracted from some plants such as Zingiberaceae and Aracerne Juss, which accounts for about 3% ~ 6% of the extracted components. The chemical structure of curcumin is C:1H»oO6, which is a diketone compound. It is a rare pigment with diketone in plant kingdom. Curcumin 1s generally orange-yellow crystalline powder with slightly bitter taste. Curcumin is insoluble in water and ether while soluble in ethanol and propylene glycol, especially in glacial acetic acid and alkali solution. Curcumin is sensitive to light and thermions thus it has poor light resistance and heat resistance. It should be loaded in brown bottles, stored in a dark place at low temperature and normal temperature. Curcumin is sensitive to iron ions and has poor iron resistance, because it can form red chelates with iron ions. Curcumin is a kind of plant polyphenol extracted from Rhizoma Curcumae Longae, and it is also the most important active ingredient of Rhizoma Curcumae Longae. Recent studies have not only proved the traditional effects of Rhizoma Curcumae Longae, but also revealed some new pharmacological effects, such as anti-
inflammatory, anti-oxidation, scavenging oxygen free radicals, anti-human immunodeficiency virus, protecting liver and kidney, anti-fibrosis, anti-cancer as well as little toxic and side effects.
However, although curcumin has a wide range of uses and high medicinal value, it is insoluble in water, absorbed less in human body and metabolized quickly, which greatly limits the application of curcumin. In recent years, the research and development of curcumin focused on how to improve the bioavailability of curcumin and prolong its action time in human body.
SUMMARY According to the invention, curcumin is prepared into curcumin clathrate, and then the curcumin clathrate is combined with a temperature sensitive gel technology, so that the problem of low bioavailability of curcumin in the prior art is solved, and a new application of curcumin as a medicine is discovered.
To achieve the above purpose, the present invention provides the following scheme: A curcumin clathrate temperature sensitive gel comprises curcumin clathrate, temperature sensitive hydrogel material and thickener.
As a further optimization of the invention, the mass concentration of curcumin clathrate in the curcumin clathrate temperature sensitive gel is 1-5%; The curcumin clathrate comprises curcumin, d-borneoi and PB-cyclodextrin, The temperature sensitive hydrogel material comprises poloxamer 407 and poloxamer 188; And the thickener is carbomer.
As a further optimization of the invention, the weight ratio of curcumin, d- borneol and B-cyclodextrin in the curcumin clathrate is 5-10: 2-3: 15-27.
As a further optimization of the invention, the weight ratio of curcumin, d- borneol and B-cyclodextrin in the curcumin clathrate is 2: 1: 8.
The invention also provides a preparation method of the curcumin clathrate, which comprises the following specific steps: (1) Weighing curcumin, d-börneol and B-cyclodextrin, pour them into a dry grinding dish, and then fully grind them with small and uniform strength; (2) Lightly pouring the mixture in step (1) into a dry 250ml conical flask, adding 50ml distilled water into the conical flask to dissolve the mixture, performing ultrasonic treatment to seal the bottle mouth of the conical flask, and magnetically rotating the conical flask; (3) Performing vacuum filtration on the liquid in the conical flask after the magnetic rotation in the step (2); (4) Performing solvent evaporation on the solution obtained by suction filtration in the step (3); (5) The residual solution evaporate in the step (4) is poured into a dry wide- mouth contain. Vacuum dry the container for 24h. A thin film is formed on the vessel wall to obtain curcumin clathrate.
As a further optimization of the invention, the ultrasonic treatment time in step (2) is 5-10 min; And the magnetic rotation is that the conical flask is placed on a magnetic rotating stirrer for magnetic rotation for 40 to 50 hours.
As a further optimization of the present invention, the evaporation in step (4) is reduced-pressure rotary evaporation, in which evaporation is stopped when the solution volume 1s 30% of the original solution volume.
The invention also provides a preparation method of the curcumin clathrate temperature sensitive gel, which comprises the following specific steps: (a) Weighing poloxamer 407, poloxamer 188 and carbomer and adding distilled water to prepare a mixed solution, wherein the mass concentration of poloxamer 407 is 20-25%, the mass concentration of poloxamer 188 is 15-20% and the mass concentration of carbomer is 0.1-0.5%, and refrigerating the mixed solution in a refrigerator at 4°C for 24-36 hours; (b) Adding curcumin clathrate into the refrigerated mixed solution in step (a), stirring and standing to obtain curcumin clathrate temperature sensitive gel.
As a further optimization of the invention, the mass concentration of poloxamer 407, poloxamer 188 and carbomer in the solution in step (a) is 24%, 16% and 0.1%, respectively.
As a further optimization of the present invention, the stirring time in step (b) is 10-15 min, and the standing time is 30-90 min.
The invention also provides an application of the curcumin clathrate temperature sensitive gel in preparing medicines for treating skin wounds.
As a further optimization of the present invention, the skin wounds include skin burns, laser burns and abrasions.
Because the preparation of thermosensitive gel is generally dissolved in water,
curcumin and D-borneol are insoluble in water, so it is difficult to prepare them under the same conditions. Therefore, curcumin was prepared into inclusion compound in this experiment, which is soluble in water, and curcumin and d-borneol can be loaded on gel carrier. Curcumin clathrate refers to the clathrate formed by curcumin and D- borneol molecules embedded in the cavity structure of B-cyclodextrin, and curcumin and D-borneol drugs as guest molecules are enclosed in the main molecule P- cyclodextrin to form molecular capsules. After inclusion, the physical and biological properties of drugs, which includs solubility, dissolution rate and oral bioavailability are changed.
The invention discloses the following technical effects: According to the invention, curcumin and d-barneol are used as additives, and the thermosensitive gel is used as a carrier to prepare curcumin thermosensitive gel. D-borneol can improve the transdermal absorption of curcumin, relieve the pain of patients and improve the bioavailability of curcumin. The temperature sensitive gel can be applied to the treatment of skin wounds, especially for skin burns and scalds, and can promote the absorption and utilization of drugs. The curcumin clathrate thermosensitive gel can be coated on a wound, and the synergistic effect of medicinal components can promote wound healing and relieve pain of patients. The formulation of the invention is simple and feasible, and the prepared temperature-sensitive gel is stable and difficult to deteriorate which is suitable for industrial production.
DESCRIPTION OF THE INVENTION Various exemplary embodiments of the present invention will be described in detail, which should not be regarded as a limitation of the present invention, but rather as a more detailed description of certain aspects, characteristics and embodiments of the present invention.
It should be understood that the terms described in the present invention are only for describing specific embodiments, and are not intended to limit the present invention. In addition, as for the numerical range in the present invention, it should be understood that every intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Intermediate values within any stated value or stated range and every smaller range between any other stated value or intermediate values within the stated range are also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded from the range.
Unless otherwise stated, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art to which the present invention relates. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe methods and/or materials related to the documents. In case of conflict with any incorporated documents, the contents of this specification shall prevail.
Without departing from the scope or spirit of the invention, it is obvious to those skilled in the art that many modifications and changes can be made to the specific embodiments of the specification of the invention. Other embodiments derived from the description of the present invention will be apparent to the skilled person. The specification and examples of this application are only exemplary.
As used herein, "including", "includs", "have", "containing", etc. are all open terms, which means including but not limited to.
Example 1 (1) Weighed curcumin, d-borneol and B-cyclodextrin in turn according to the weight ratio of 2: 1: 8, poured into a dry grinding dish, and then fully grinded with small and uniform strength.
(2) Lightly poured the mixture in step (1) into a dry 250 ml conical flask, added 50 ml of distilled water into the conical flask to dissolve the mixture. Put the conical flask into a numerical control ultrasonic cleaner for ultrasonic vibration for 5 minutes, then sealed the flask mouth with plastic wrap, and placed the conical flask on a magnetic rotating stirrer for magnetic rotation for 48 hours.
(3) Took vacuum filtration on the liquid in the conical flask after the magnetic rotation in the step (2); (4) Took rotary evaporation on the solution obtained by suction filtration in step (3) under reduced pressure, and stopped evaporation when the volume of the solution was 30% of the volume of the original solution.
(5) The residual solution evaporated in step (4) was poured into a dry wide- mouth contain. Placed the container in a vacuum drying oven for drying for 24 h. A thin film was formed on the vessel wall to obtain curcumin clathrate.
(6) Weighted poloxamer 407, poloxamer 188 and carbomer and added 100ml distilled water to prepare a solution, wherein the mass concentration of poloxamer 407 is 24% while the mass concentration of poloxamer 188 was 16% and the mass concentration of carbomer was 0.1%, then refrigerated the mixed solution in a refrigerator at 4°C for 26 hours.
(7) Added 4 g of curcumin clathrate obtained in step (5) into the mixed solution obtained in step (6), slowly stirred for 10 min, and stood for 50 min to obtain curcumin clathrate temperature sensitive gel with the curcumin clathrate mass concentration of 4%.
Example 2 (1) According to the weight ratio of 10: 2: 15, curcumin, D-borneol and P- cyclodextrin were weighed in turn, poured into a dry grinding dish, and then fully grinded with small and uniform strength.
(2) Lightly poured the mixture in step (1) into a dry 250ml conical flask, added 50ml distilled water into the conical flask to dissolve the mixture, put the conical flask into a numerical control ultrasonic cleaner for ultrasonic vibration for 8 min, sealed the flask mouth with plastic wrap, and placed it on a magnetic rotating stirrer for magnetic rotation for 40 hours.
(3) Took vacuum filtration on the liquid in the conical flask after the magnetic rotation in the step (2); (4) Took rotary evaporation on the solution obtained by suction filtration in step (3) under reduced pressure, and stopped evaporation when the volume of the solution was 30% of the volume of the original solution.
(5) The residual solution evaporated in the step (4) was poured into a dry wide- mouth contain. Placed the container in a vacuum drying oven for drying for 24 hours. À thin film was formed on the vessel wall to obtain curcumin clathrate.
(6) The poloxamer 407, poloxamer 188 and carbomer were weighed and added with 100ml distilled water to prepare a solution, in which the mass concentration of poloxamer 407 was 20%, the mass concentration of poloxamer 188 was 20% and the mass concentration of carbomer was 0.3%, and the mixed solution is refrigerated in a refrigerator at 4°C for 36 hours.
(7) Added 5 g of curcumin clathrate obtained in step (5) into the mixed solution obtained in step (6), slowly stirred for 15 min, and stood for 30 min to obtain curcumin clathrate temperature sensitive gel with the curcumin clathrate mass concentration of 5%.
Example 3 (1) Weighed curcumin, d-borneol and B-cyclodextrin in turn according to the weight ratio of 5: 2: 27, poured into a dry grinding dish, and then fully grind with small and uniform strength; (2) Lightly poured the mixture in step (1) into a dry 250ml conical flask, added 50ml distilled water into the conical flask to dissolve the mixture, put the conical flask into a numerical control ultrasonic cleaner for ultrasonic vibration for 10 min, sealed the flask mouth with plastic wrap, and placed the conical flask on a magnetic rotating stirrer for magnetic rotation for 50 hours;
(3) Took vacuum filtration on the liquid in the conical flask after the magnetic rotation in the step (2); (4) Subjected the solution obtained by suction filtration in step (3) to rotary evaporation under reduced pressure, and stopped evaporation when the solution volume was 30% of the original solution volume; (5) The residual solution evaporated in step (4) was poured into a dry wide- mouth contain. Placed the container in a vacuum drying oven for drying for 24 hours. Formed a film on the vessel wall to obtain curcumin clathrate: (6) Weighed poloxamer 407, poloxamer 188 and carbomer then added 100ml distilled water to prepare a solution, wherein the mass concentration of poloxamer 407 was 25%, the mass concentration of poloxamer 188 was 15% and the mass concentration of carbomer was 0.5%, then refrigerated the mixed solution in a refrigerator at 4 °C for 24 hours; (7) Added 2 g of curcumin clathrate obtained in step (5) into the mixed solution obtained in step (6), slowly stirred for 12 min, and stood for 90 min to obtain curcumin clathrate temperature sensitive gel with the curcumin clathrate mass concentration of 2%.
Example 4 (1) Weighed curcumin, d-borneot and B -cyclodextrin in turn according to the weight ratio of 7: 2: 27, and poured it into a dry grinding dish, and then fully grinded with small and uniform strength.
(2) Lightly poured the mixture in step (1) into a dry 250ml conical flask, added
50 ml of distilled water into the conical flask to dissolve the mixture, put the conical flask into a numerical control ultrasonic cleaner for ultrasonic vibration for 9 min; Then sealed the flask mouth with plastic wrap, and placed it on a magnetic rotating stirrer for magnetic rotation for 41 hours.
(3) Took vacuum filtration on the liquid in the conical flask after the magnetic rotation in the step (2); (4) Took rotary evaporation on the solution obtained by suction filtration in step (3) under reduced pressure, and stopped evaporation when the volume of the solution was 30% of the volume of the original solution.
(5) The residual solution evaporated in that step (4) was poured into a dry wide- mouth contain. Placed the container in a vacuum drying oven for drying for 24 hours. À thin film was formed on the vessel wall to obtain curcumin clathrate.
(6) Weighed poloxamer 407, poloxamer 188 and carbomer and added 100ml distilled water to prepare a solution, wherein the mass concentration of poloxamer 407 is 21%, the mass concentration of poloxamer 188 is 19% and the mass concentration of carbomer is 0.2%; Then placed the mixed solution in a refrigerator at 4°C for 29 hours.
(7) Added 3 g of curcumin clathrate obtained in step (5) into the mixed solution obtained in step (6), slowly stirred for 11 min, and stood for 40 min to obtain curcumin clathrate temperature sensitive gel with the curcumin clathrate mass concentration of 3%.
Example 5
(1) Weighed curcumin, d-borneel and B-cyclodextrin in turn according to the weight ratio of 6: 2: 23, and then poured into a dry grinding dish, and then fully grinded with small and uniform strength.
(2) Lightly poured the mixture in step (1) into a dry 250ml conical flask, adding 50 ml distilled water into the conical flask to dissolve the mixture; Put the conical flask into the numerical control ultrasonic cleaner for ultrasonic vibration for 5 min, sealed the flask mouth with plastic wrap, and put the conical flask on the magnetic rotating stirrer for magnetic rotation for 45 hours.
(3) Took vacuum filtration on the liquid in the conical flask after the magnetic rotation in the step (2).
(4) Took rotary evaporation on the solution obtained by suction filtration in step (3) under reduced pressure, and stopped evaporation when the volume of the solution was 30% of the volume of the original solution.
(5) The residual solution evaporated in step (4) was poured into a dry wide- mouth contain. Placed the container in a vacuum drying oven for drying for 24 hours. A thin film was formed on the vessel wall to obtain curcumin clathrate.
(6) Weighed poloxamer 407, poloxamer 188 and carbomer, added 100 ml distilled water to prepare a solution, wherein the mass concentration of poloxamer 407 was 23%, the mass concentration of poloxamer 188 was 16% and the mass concentration of carbomer was 0.1%, then refrigerated the mixed solution in a refrigerator at 4°C for 31 hours.
(7) Added 1 g of curcumin clathrate obtained in step (5) into the mixed solution obtained in step (6), slowly stirred for 10 min, and stood for 30 min to obtain curcumin clathrate temperature sensitive gel with the curcumin clathrate mass concentration of 1%.
Example 6 The preparation method was the same as Example 1, except that 1 g of curcumin clathrate obtained in step (5) was added to the mixed solution obtained in step (6) in step (7).
In this example, the curcumin clathrate temperature sensitive gel with 1% curcumin clathrate mass concentration was obtained.
Example 7 The preparation method was the same as Example 1, except that 2 g of curcumin clathrate obtained in Step (5) was added to the mixed solution obtained in Step (6) in Step (7).
In this example, the curcumin clathrate temperature sensitive gel with the mass concentration of curcumin clathrate of 2% was obtained.
Example 8 The preparation method was the same as Example 1, except that 3 g of curcumin clathrate obtained in Step (5) was added to the mixed solution obtained in Step (6) in Step (7).
In this example, a curcumin clathrate temperature sensitive gel with a curcumin clathrate mass concentration of 3% was obtained.
Example 9
The preparation method was the same as Example 1, except that 5 g of curcumin clathrate obtained in Step (5) was added to the mixed solution obtained in Step (6) in Step (7).
In this example, a curcumin clathrate temperature sensitive gel with a curcumin clathrate mass concentration of 5% was obtained.
Example 10 Weighed poloxamer 407, poloxamer 188 and carbomer into 100ml distilled water to prepare a solution, in which the concentration of poloxamer 407 was 24%, the concentration of poloxamer 188 was 16% and the concentration of carbomer was
0.1%. Sealed and put the sample in a refrigerator at 4°C for 26 hours to obtain a blank gel matrix, in which the mass concentration of curcumin clathrate was 0%.
Comparative example 1 The preparation method was the same as that of Example 1, except that the corresponding components of D-borneol were not added in step (1).
Comparative example 2 The preparation method was the same as Example 1, except that curcumin of corresponding components was not added in step (1).
Embodiment 1 Solubility test of curcumin and curcumin clathrate Added 10 ml of distilled water into two dry 100ml beakers, add equal amount of curcumin and curcumin clathrate obtained in step (5) of Example 1 to the beakers respectively, stired with glass rods, and observed the dissolution in the two beakers. If both of them are dissolved, continue to add the same amount of curcumin and curcumin clathrate into the beaker until one of them 1s completely dissolved and the other is precipitated. Through observation, it can be concluded that curcumin is basically in an insoluble state in water, which 1s basically transparent in water and has a large number of suspended particles, However, curcumin clathrate was almost completely dissolved in water and the solution was orange-yellow. According to the difference, it can be concluded that the solubility of curcumin clathrate is greater than curcumin. However, human body contains a lot of water, so that if we want to make use of the efficacy of curcumin for human body, it is difficult to be accepted from the solubility point of view, while curcumin clathrate is easily soluble in water and can be well absorbed in human body.
Embodiment 2 Test tube inversion method was used. The blank gel matrix in Example 10 and curcumin clathrate gels prepared in Example 1 and Examples 6-9 with mass concentrations of 4%, 1%, 2%, 3% and 5% were respectively transferred to a vial for 3-5 ml. Put the vial filled with temperature sensitive gel substance into a digital display constant temperature water bath pot, insert a thermometer, and raised the temperature at a rate of 0.4°C/min until the gel stopped flows, at which time the corresponding temperature was the gel temperature. Measured three times and took the average value. The experimental results were shown in Table 1 below.
Table 1 Effect of curcumin clathrate with different mass concentration on phase transition temperature and gel time of blank gel matrix Concentration of | Phase transition | Gel time /min curcumin temperature /"C clathrate% oo | SAT | 5107 It can be seen from Table 1 that when curcumin clathrate was added to the blank gel matrix, both the phase transition temperature of the gel matrix and the gel decreased. The phase transition temperature of the gel matrix decreased from 54.7°C to 45.9°C with the increase of the mass concentration of curcumin clathrate. The gel time also decreased from 5 minutes and 7 seconds to 2 minutes and 45 seconds with the increase of the mass concentration of inclusion compound. This may due to the clathrate promotes the entanglement and stacking of poloxamer molecules, which leads to the decrease of phase transition temperature and gel time.
Moreover, observing the inverted vial, it can be seen that with the increase of the concentration of curcumin clathrate, the color of the gel formed gradually deepens. When the concentration of curcumin clathrate reaches 5%, the viscosity of the gel is not strong enough. After a long time of inversion, the liquid surface of the gel will slide down along the wall of the vial.
Embodiment 3
Detection of performance parameter of gels prepare in Examples 1-9: The performance parameters of curcumin clathrate thermosensitive gels prepared in Examples 1-9 were tested, and the products in Examples 1-9 met the following requirements:
1. Properties: The curcumin clathrate thermosensitive gel prepared in Examples 1-9 1s colorless to yellow, transparent gel, with uniform and delicate texture, proper consistency and good spreadability.
2. PH: Take a few samples from Examples 1 ~ 9, and the pH measured by precision pH test paper is between 6 ~ 8. The curcumin clathrate thermosensitive gel prepared in Examples 1 ~ 9 meets the requirements of topical ointment in Chinese Pharmacopoeia.
3. Bacterial determination of gel itself: Methods According to GB15980-1995. The results showed that the curcumin clathrate thermosensitive gels prepared in Examples 1-9 were sterile.
4. Beasurement of primary irritation index (PII): According to the method specified in GB/T16886.10-2000, acute exposure for 24 hours is required, and the index is no more than 0.5. The results showed that the curcumin clathrate thermosensitive gels prepared in Examples 1-9 met the requirements.
5. Determination of skin sensitization reaction: According to the closed sensitization test method specified in GB/T16886.10-2000, there was no skin sensitization reaction. The results showed that the curcumin clathrate thermosensitive gels prepared in Examples 1-9 did not cause skin sensitization reaction.
Embodiment 4 Antibacterial experiment in vitro According to the operation of Regulation of Disinfection Technique (2002 edition) issued by the Ministry of Health, in vitro antibacterial experiments were carried out on the thermosensitive gels prepared in Examples 1-10 and Comparative Examples 1-
2. The experimental method was to prepare bacterial suspensions with a concentration of 105-106 cfu/ml. Added 0.1 mL of bacterial suspension to the specified amount of samples, mixed well and let stand for 20 minutes, then dilute it; Took 0.5 mL of it into sterile plate, poured 15 ~ 20 ml of sterile agar medium at 40°C ~ 50°C, and cultured at 37°C for 48 ~ 72 h, counted bacteria.
The results are shown in Table 2. When the bacteriostatic rate is > 50%, the samples have bacteriostatic effect.
Table 2 Results of in vitro antibacterial experiment (killing rate of bacteria after min, %) Bacteria (105 ~ Candida Escherichia Staphylococcus Pseudomonas albicans coli aureus aeruginosa 10° CFU/mL) Example | Example? Example Example4 Examples Example6 Example7 Example8 Example 9 Exampleto | 0 |0 Jo | 0 Comparative 100 100 100 100 example 1 Comparative example 2 Test example 5 Detection of clinical treatment effect The temperature-sensitive gel skin burn patients of Examples 1-9 and Comparative Examples 1-2 were tested, and the test scheme was as follows: The number of cases used for each sample is the number in parentheses after each example and comparative example in Table 3. Use it once every 4 h every day, or as needed, until the wound heals, and observe the use effect.
Usage: Put a proper amount of gel on clean fingers or cotton swabs and apply it on the wound surface.
Table 3 fs | Forth day | Twelfth day Sixth day | Thrtieth day Healing rate of bum| 59 100 E le 1 surface % xample : . Pain relief (21) PA Scar rate, % > Healing rate of bum| 42 72 100 surface % Example 2 | Pain relief (20) rate, % 100 100 100 Scar rate, % Healing rate of bum| 46 75 100 surface % Example 3 | Pain relief (18) rate, % 100 100 100 Scar rate, % 7 Healing rate of burn | 43 79 100 surface % Example 4 | Pain relief (19) rate, % 100 100 100 Scar rate, % 7 Healing rate of bum| 46 82 100 Example 5 surface % (22) Pain relief rate, % 100 100 100
S LU500473 car Healing rate of burn | 40 75 100 surface % Example 6 | Pain relief (23) rate, % 100 100 100 Scar rate, % Healing rate of burn | 41 77 100 surface % Example 7 | Pain relief (21) rate, % 100 100 100 Scar rate, % Healing rate of burn | 55 100 surface % Example 8 | Pain relief (24) rate, % 100 100 100 Scar rate, % Healing rate of burn 88 100 surface % Example 9 | Pain relief (20) rate, % 100 100 100 Scar rate, % > . Heali t Comparative FAIR rate mole 1 of burn KAMPIS | surface % 19 59 82 100 (21)
Pain relief LU500473 rate, % 11 45 63 100 Scar rate, % 20 Healing rate of burn 5 11 20 45 . surface % Comparative : ; example 2 Pain relief x P rate % 20 49 72 85 (22) Scar rate, %
The above embodiments and examples only describe the preferred mode of the invention, but do not limit the scope of the invention.
On the premise of not departing from the design spirit of the invention, various modifications and improvements made by ordinary technicians in the field to the technical scheme of the invention shall fall within the protection scope determined by the claims of the invention.

Claims (10)

CLAIMS:
1. A curcumin clathrate temperature sensitive gel is characterized by comprising curcumin clathrate, temperature sensitive hydrogel material and thickener.
2. The curcumin clathrate temperature sensitive gel according to claim 1 is characterized in that the mass concentration of curcumin clathrate in the curcumin clathrate temperature sensitive gel is 1-5%; the curcumin clathrate compound comprises curcumin, d-borneol and P- cyclodextrin; the temperature sensitive hydrogel material comprises poloxamer 407 and poloxamer 188; the thickener is carbomer.
3. The curcumin clathrate temperature sensitive gel according to claim 2 is characterized in that the weight ratio of curcumin, d-borneol and ß -cyclodextrin in the curcumin clathrate 1s 5-10: 2-3: 15-27 in turn.
4. The curcumin clathrate temperature sensitive gel according to claim 3 is characterized in that the weight ratio of curcumin, d-borneol and beta-cyclodextrin in the curcumin clathrate 1s 2: 1: 8 in turn.
5. The curcumin clathrate temperature sensitive gel according to claim 1 is characterized in that the preparation method of the curcumin clathrate comprises the following steps: (1) weighing curcumin, d-borneel and P-cyclodextrin, pour them into a dry grinding dish, and then fully grind them with small and uniform strength; (2) lightly pouring the mixture in step (1) into a dry 250ml conical flask, adding 50ml distilled water into the conical flask to dissolve the mixture, performing ultrasonic treatment to seal the bottle mouth of the conical flask, and magnetically rotating the conical flask; (3) performing vacuum filtration on the liquid in the conical flask after the magnetic rotation in the step (2); (4) performing solvent evaporation on the solution obtained by suction filtration in the step (3); (5) the residual solution evaporate in the step (4) is poured into a dry wide-mouth contain; vacuum dry the container for 24h; a thin film is formed on the vessel wall to obtain curcumin clathrate.
6. The curcumin clathrate thermosensitive gel according to claim 5, which is characterized in that the ultrasonic treatment time in step (2) is 5-10 min; and the magnetic rotation is that the conical flask is placed on a magnetic rotating stirrer for magnetic rotation for 40 to 50 hours.
7. A preparation method of curcumin clathrate compound temperature sensitive gel according to any one of claims 1- 6 is characterized by comprising the following specific steps: (a) weighing poloxamer 407, poloxamer 188 and carbomer and adding distilled water to prepare a mixed solution, wherein the mass concentration of poloxamer 407 is 20-25%, the mass concentration of poloxamer 188 is 15-20% and the mass concentration of carbomer is 0.1-0.5%, and refrigerating the mixed solution in a refrigerator at 4°C for 24-36 hours; (b) adding curcumin clathrate into the refrigerated mixed solution in step (a), stirring and standing to obtain curcumin clathrate temperature sensitive gel.
8. The preparation method of temperature sensitive gel according to claim 7 1s characterized in that the stirring time in step (b) is 10-15 min, and the standing time is 30-90 min.
9. The application of the curcumin clathrate temperature sensitive gel according to any one of claims 1- 6 is characterized by the application of the curcumin clathrate temperature sensitive gel in preparing drugs for treating skin wounds.
10. The application of the temperature sensitive gel according to claim 9 is characterized in that the skin wound comprises skin burns, laser burns and abrasions.
! LU500473
PATENTANSPRÜCHE
1. Ein temperaturempfindliches Gel von Curcumin-Einschlussverbindung ist dadurch gekennzeichnet, dass es Curcumin-Einschlussverbindung, temperaturempfindliches Hydrogelmaterial und Verdickungsmittel umfasst.
2. Das temperaturempfindliche Gel von Curcumin-Einschlussverbindung nach Anspruch 1 ist dadurch gekennzeichnet, dass die Massenkonzentration von Curcumin-Einschlussverbindung im temperaturempfindlichen Gel von Curcumin-Einschlussverbindung 1-5% beträgt; die Curcumin-Einschlussverbindung umfasst Curcumin, d-Borneol und B-Cyclodextrin; das temperaturempfindliche Hydrogelmaterial besteht aus Poloxamer 407 und Poloxamer 188; das Verdickungsmittel ist Carbomer.
3. Das temperaturempfindliche Gel von Curcumin-Einschlussverbindung nach Anspruch 2 ist dadurch gekennzeichnet, dass das Gewichtsverhältnis von Curcumin, d-Borneol und P- Cyclodextrin im Curcumin-Einschlussverbindung 5-10: 2-3: 15-27 beträgt.
4. Das temperaturempfindliche Gel von Curcumin-Einschlussverbindung nach Anspruch 3 ist dadurch gekennzeichnet, dass das Gewichtsverhältnis von Curcumin, d-Borneol und beta- Cyclodextrin im Curcumin-Einschlussverbindung wiederum 2: 1: 8 beträgt.
5. Das temperaturempfindliche Gel von Curcumin-Einschlussverbindung nach Anspruch 1 ist dadurch gekennzeichnet, dass das Herstellungsverfahren der Curcumin-Einschlussverbindung die folgenden Schritte umfasst: (1) Curcumin, d-Borneol und B-Cyclodextrin abwiegen, in einen trockenen Mahlteller gießen und dann vollauf mahlen; (2) gieBen der Mischung in Schritt (1) in einen trockenen Erlenmeyerkolben, hinzufügen von 50 ml destilliertem Wasser in den Erlenmeyerkolben, um die Mischung aufzulôsen; Durchführen einer Ultraschallbehandlung, Versiegeln der Flaschenôffnung des Erlenmeyerkolbens, magnetisches Drehen des Erlenmeyerkolbens;
(3) durchführen einer Vakuumfiltration an der Flüssigkeit im Erlenmeyerkolben nach dem magnetischen Drehen in Schritt (2); (4) durchführen einer Verdampfung des Lôsungsmittels an der durch Saugfiltration in Schritt (3) erhaltenen Lösung; (5) die in Schritt (4) verdampfte Restlösung wird in einen trockenen Weithalsbehälter gegossen; den Behälter für 24 h vakuumtrocknen; es bildet sich ein dünner Film an der Wand des Behälters, um Curcumin-Einschlussverbindung zu erhalten.
6. Das temperaturempfindliche Gel von Curcumin-Einschlussverbindung nach Anspruch 5 ist dadurch gekennzeichnet, dass die Ultraschallbehandlung in Schritt (2) 5-10 min dauert; die magnetische Rotation darin besteht, dass der Erlenmeyerkolben zur magnetischen Rotation für 40 bis 50 Stunden auf einen magnetischen rotierenden Rührer gestellt wird.
7. Verfahren zur Herstellung des temperaturempfindlichen Gels von Curcumin- Einschlussverbindung nach einem der Ansprüche 1 bis 6 ist dadurch gekennzeichnet, dass es die folgenden spezifischen Schritte umfasst: (a) Abwiegen von Poloxamer 407, Poloxamer 188 und Carbomer und Zugeben von destilliertem Wasser, um eine gemischte Lösung herzustellen, wobei die Massenkonzentration von Poloxamer 407 20-25%, die Massenkonzentration von Poloxamer 188 15-20% und die Massenkonzentration von Carbomer 0,1-0,5% beträgt; Kühlen der gemischten Lösung im Kühlschrank bei 4°C für 24-36 Stunden; (b) Zugabe von Curcumin-Einschlussverbindung in die in Schritt (a) gekühlte gemischte Lösung, Rühren und Stehenlassen, um das temperaturempfindliche Gel von Curcumin- Einschlussverbindung zu erhalten.
8. Das Herstellungsverfahren von temperaturempfindlichem Gel nach Anspruch 7 ist dadurch gekennzeichnet, dass die Rührzeit in Schritt (b) 10-15 min und die Ruhezeit 30-90 min beträgt.
9. Anwendung des temperaturempfindlichen Gels von Curcumin-Einschlussverbindung nach einem der Ansprüche 1-6 ist dadurch gekennzeichnet, dass das temperaturempfindliche Gel von Curcumin-Einschlussverbindung zur Herstellung von Arzneimitteln zur Behandlung von Hautwunden verwendet wird.
10. Die Anwendung des temperaturempfindlichen Gels nach Anspruch 9 ist dadurch gekennzeichnet, dass die Hautwunde Hautverbrennungen, Laserverbrennungen und Abschiirfungen umfasst.
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