A breviscapine organic gel and a preparation method thereof

Abstract

The application provides a breviscapine organic gel and a preparation method thereof. The breviscapine organic gel uses an organic solvent system as a dispersion medium, and the breviscapine is both an active ingredient and a gel factor, and no additional gel material is needed. The preparation method is simple and efficient, and the obtained gel can be used for further processing into corresponding preparations for treating local or systemic diseases. The breviscapine gel prepared by the application has high drug loading, better transdermal penetration and skin retention effect, simple formula, simple preparation method, and is beneficial to realize industrial production and application.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine, in particular to a breviscapine organic gel and a process for preparing the breviscapine organic gel. BACKGROUND

[0002] Erigeron breviscapus (Vant.) Hand.-Mazz. is a dry whole plant of the Compositae family. It is a traditional medicine of the Miao and Yi ethnic groups in Yunnan Province. It has a bitter and slightly bitter taste, and is warm in nature. It is used for treating stroke, chest pain, rheumatic arthralgia, headache, toothache, etc. Breviscapine is mainly extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. Breviscapine is almost insoluble in water (<1mg / ml), and even less soluble in most organic solvents (such as dichloromethane, ethyl acetate, etc.). The solubility of breviscapine in methanol and ethanol is less than 5mg / ml, which brings great inconvenience to its disposal and application.

[0003] The existing Erigeron breviscapus and breviscapine related listed drugs are mainly oral preparations, and there are only 5 kinds of external preparations, all of which are compound preparations, involving gel, liniment, aerosol, tincture, etc. Among them, only one kind of gel, "tumor pain gel", contains 19 ingredients. It is made of high-concentration ethanol as solvent and polyvinyl alcohol as gel material, and can form a film on the skin after application. It is mainly used for treating contusion, rheumatic arthralgia, shoulder periarthritis, gout, and lobular hyperplasia of the breast. Therefore, the exploration and application of Erigeron breviscapus external function are far from enough, especially the lack of simple and efficient gel external preparation using breviscapine as raw material.

[0004] Gels are a common dosage form, which are easy to prepare, convenient to use, strong in containment, and can be applied by smearing, pasting, filling and other ways when used externally, for human skin, mucosa, cavity and other parts. At present, external use gel preparations usually select polyvinyl alcohol, carbomer, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, polysaccharide and other high molecular materials, and mainly water gel. In the process of preparing gels, the above gel materials are usually dispersed in water to form a gel after swelling, and then drugs and other components of the prescription are added and mixed to form a gel. Colloidal particles or polymers are connected to each other under certain conditions to form a space network structure, and the structure gap is filled with liquid as a dispersion medium. Such a special dispersion system is called gel. It usually has no or low flowability. It often contains a large amount of liquid. For example, the water content of blood gel and agar can reach more than 99%. It can be divided into elastic gel and brittle gel. The volume of elastic gel significantly decreases when the dispersion medium is lost, and the volume expands again when the dispersion medium is reabsorbed, such as gelatin. The shape and volume of brittle gel do not change when the dispersion medium is lost or reabsorbed, such as silica gel. The process of forming a gel from a solution or sol is called gelation.

[0005] The prior art "Effect of Different Transdermal Absorption Promoters on Transdermal Absorption of Breviscapine Gels" (Fang Rui et al., Chinese Traditional and Herbal Drugs, 34(06):1174-1176, 2012) discloses a breviscapine-loaded gel and its preparation method, which uses carbomer as a gel material and adds glycerol as a humectant, azone as a transdermal absorption enhancer, and nipagin as a bacteriostatic agent. The prior art "In Vitro Release Rate Investigation of Breviscapine Microemulsion Gel" (Huang Qingde et al., Chinese Modern Applied Pharmacy, 31(10):1212-1215, 2014) discloses a breviscapine-loaded microemulsion gel and its preparation method, which dissolves breviscapine in the oil phase, adds carbomer as a gel material in the water phase, and then mixes the water and oil phases to form a microemulsion. The above gel preparation technology needs to add a large amount of specific gel material to form a gel, and forms a water gel with water as a dispersion medium, and needs to add multiple additives.

[0006] Unlike the above prior art, the present application is completed by the unexpected discovery that breviscapine has self-gelation ability. The breviscapine self-gel organic gel of the present application uses an organic solvent as a dispersion medium and does not add gel materials to form a gel. It uses conventional equipment and process, and the preparation method is simple and efficient. The obtained gel has high drug loading capacity, stable properties, and can quickly penetrate and absorb through the skin. SUMMARY

[0007] The present application aims to provide a self-gelling organic gel of scutellarein. The active ingredient scutellarein is directly used as the gel factor, and a specific organic solvent is used as the dispersion medium. The present application also aims to provide a preparation method of the self-gelling organic gel of scutellarein, which is simple and controllable. The present inventors surprisingly found that scutellarein has the self-gelling ability. Non-limitatively, the present inventors believe that the self-gelling ability of scutellarein is due to the molecular interaction between scutellarein molecules and between scutellarein molecules and the solvent. That is, after scutellarein is sufficiently dissolved in a good solvent, it is uniformly dispersed in a poor solvent. As the solubility decreases, scutellarein precipitates. The molecules of scutellarein are crosslinked with each other through the hydroxyl groups and other groups, forming a spatial network structure. The structure gap is filled with the solvent, thereby forming a gel containing only scutellarein and the solvent.

[0008] Specifically, the present application provides the following technical solutions:

[0009] A self-gelling organic gel of scutellarein, characterized in that it is composed of only scutellarein and an organic solvent, and no other gel material. The scutellarein is used as both the active ingredient and the gel factor. The organic solvent is substantially a poor solvent for scutellarein.

[0010] The organic solvent being substantially a poor solvent for scutellarein means that the organic solvent as a whole exhibits the property of a poor solvent, i.e., scutellarein is insoluble or hardly soluble in the organic solvent. For example, although a good solvent is used in the preparation of the self-gelling organic gel of scutellarein, the good solvent can be removed in the final product. Understandably, the good solvent can also not be removed. However, since the relative amount of the good solvent is small, the poor solvent accounts for the majority in the whole organic solvent system, so that the organic solvent as a whole exhibits the property of a poor solvent.

[0011] The content of scutellarein in the organic gel has a certain degree of influence on the properties of the organic gel. Non-limitatively, the present inventors believe that when the content of scutellarein is particularly low, the interaction between the molecules is weak, and the network structure is not stable, so that a good gel state can not be formed. Preferably, the content of scutellarein is greater than or equal to 2% by weight of the gel, and the gel obtained at this time has excellent properties.

[0012] More preferably, the content of scutellarein is greater than or equal to 4% by weight of the gel.

[0013] In the case where the good solvent in the organic solvent is not removed, the organic solvent is composed of a good solvent and a poor solvent for scutellarein. The amount of the good solvent is sufficient to dissolve the scutellarein in the gel, and the amount of the poor solvent is sufficient to disperse the solution of the good solvent in which scutellarein is dissolved.

[0014] Correspondingly, the good solvent in the organic solvent can also be removed, and the removal method is a conventional method in the art, such as evaporation, dialysis, extraction, displacement and the like. After the good solvent is removed, the obtained organic solvent is a poor solvent of scutellarein.

[0015] Further preferably, the poor solvent is one or more of dichloromethane, n-butanol, n-octanol, acetonitrile, glycerol, dioxane and trifluoroacetic acid.

[0016] More preferably, the poor solvent is one or more of dichloromethane and glycerol.

[0017] Preferably, the good solvent is one or more of dimethyl sulfoxide, pyridine, N-methyl pyrrolidone, N,N-diethylacetamide and N,N-dimethylformamide.

[0018] More preferably, the good solvent is dimethyl sulfoxide.

[0019] Preferably, the weight ratio of the good solvent to the poor solvent is 1:19-1:7.

[0020] The present application also provides a preparation method of the scutellarein self-gelling organic gel, characterized in that: a reverse-solvent precipitation method is used to prepare the gel, i.e. an appropriate amount of scutellarein raw material is weighed, a good solvent is added to completely dissolve the scutellarein, and then the good solvent is mixed with a poor solvent uniformly, and the good solvent is removed or not removed, to obtain the gel.

[0021] Preferably, when the good solvent is dimethyl sulfoxide, the good solvent is not removed. Partially, the reason is that dimethyl sulfoxide has the property of transdermal absorption and the like, which is beneficial to topical administration.

[0022] Preferably, an auxiliary means such as ultrasonic or high-speed shearing is used to mix the good solvent and the poor solvent uniformly. Preferably, the auxiliary means is ultrasonic.

[0023] A scutellarein organic gel, which does not flow down when the container is inverted, or the viscosity ratio of the system to the used solvent is not less than 10, or the ratio of the storage modulus (G') to the loss modulus (G") of the system in the rheological test is not less than 10.

[0024] The scutellarein organic gel preparation method provided by the present application is simple, low in price and good in reproducibility.

[0025] In summary, the inventors have found, through unexpected research, that a proper organic solvent system can be used to prepare a scutellarein gel, without adding a gel material to form a high-strength gel preparation by itself, and the transdermal penetration performance is also improved. Moreover, no auxiliary materials and special equipment are needed in the above-mentioned gel preparation process, which saves cost and is convenient for large-scale production. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 Appearance of the organic gels of Example 1 and the suspensions of Comparative Examples 1, 2 and 3.

[0027] Figure 2 Rheological determination results of the organic gels of Example 1 and the suspensions of Comparative Examples 1, 2 and 3.

[0028] Figure 3 (A) X-ray powder diffraction pattern and (B) Fourier transform infrared spectrogram of the raw material of scutellarein and the organic gel of Example 1.

[0029] Figure 4 Appearance of the organic gels of Examples 2-12.

[0030] Figure 5 Appearance of the suspensions of Comparative Examples 4-22.

[0031] Figure 6 In-vitro transdermal curve and related parameters of the organic gel of Example 1 and the suspension of Comparative Example 6.

[0032] The technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. DETAILED DESCRIPTION

[0033] Example 1: Weigh the raw material of scutellarein and add appropriate amount of dimethyl sulfoxide to make it completely dissolved to form a drug solution with a concentration of 40%; mix the above solution (1 part) with dichloromethane (9 parts) under ultrasonic condition (ice bath, 600 W, 1 min) to obtain the organic gel of scutellarein (see the attached Figure 1 d).

[0034] Example 2: Weigh the raw material of scutellarein and add appropriate amount of pyridine to make it completely dissolved to form a drug solution with a concentration of 40%; mix the above solution (1 part) with dichloromethane (9 parts) under ultrasonic condition (ice bath, 600 W, 1 min) to obtain the organic gel of scutellarein (see the attached Figure 4 a).

[0035] Example 3: Weigh the raw material of scutellarein and add appropriate amount of N-methyl pyrrolidone to make it completely dissolved to form a drug solution with a concentration of 40%; mix the above solution (1 part) with dichloromethane (9 parts) under ultrasonic condition (ice bath, 600 W, 1 min) to obtain the organic gel of scutellarein (see the attached Figure 4 b).

[0036] Example 4: Weigh the breviscapine raw material into a mixture of dimethyl sulfoxide and N,N-dimethylformamide (3:1 by volume) to form a 40% drug solution. Mix the solution (1 part) with dichloromethane (9 parts) under ultrasonic conditions (ice bath, 600 W, 1 min) to obtain the breviscapine organic gel (see attached Figure 4). Figure 4 c).

[0037] Example 5: Weigh the breviscapine raw material into dimethyl sulfoxide to form a 40% drug solution. Mix the solution (1 part) with n-octanol (7 parts) under ultrasonic conditions (ice bath, 600 W, 3 min) to obtain the breviscapine organic gel (see attached Figure 5). Figure 4 d).

[0038] Example 6: Weigh the breviscapine raw material into dimethyl sulfoxide to form a 40% drug solution. Mix the solution (1 part) with n-butanol (7 parts) under ultrasonic conditions (ice bath, 600 W, 3 min) to obtain the breviscapine organic gel (see attached Figure 6). Figure 4 e).

[0039] Example 7: Weigh the breviscapine raw material into dimethyl sulfoxide to form a 40% drug solution. Mix the solution (1 part) with glycerol (19 parts) under ultrasonic conditions (ice bath, 1000 W, 5 min) to obtain the breviscapine organic gel (see attached Figure 7). Figure 4 f).

[0040] Example 8: Weigh the breviscapine raw material into dimethyl sulfoxide to form a 40% drug solution. Mix the solution (1 part) with acetonitrile (9 parts) under ultrasonic conditions (ice bath, 800 W, 3 min) to obtain the breviscapine organic gel (see attached Figure 8). Figure 4 g).

[0041] Example 9: Weigh the breviscapine raw material into dimethyl sulfoxide to form a 40% drug solution. Mix the solution (1 part) with trifluoroacetic acid (9 parts) under ultrasonic conditions (ice bath, 800 W, 1 min) to obtain the breviscapine organic gel (see attached Figure 9). Figure 4 h).

[0042] Example 10: Weigh the breviscapine raw material and add appropriate amount of dimethyl sulfoxide to make it completely dissolved to form a drug solution with a concentration of 40%; mix the above solution (1 part) with dichloromethane and trifluoroacetic acid mixed solvent (9 parts, volume ratio 1:1) under ultrasonic condition (ice bath, 100 W, 5 min) to obtain breviscapine organic gel (see attached Figure 4 i).

[0043] Example 11: Weigh the breviscapine raw material and add appropriate amount of dimethyl sulfoxide to make it completely dissolved to form a drug solution with a concentration of 40%; mix the above solution (1 part) with dichloromethane and 1,4-dioxane (7 parts, volume ratio 3:2) under high shear condition (12000 rpm, 1 min) to obtain breviscapine organic gel (see attached Figure 4 j).

[0044] Example 12: Weigh the breviscapine raw material and add appropriate amount of dimethyl sulfoxide to make it completely dissolved to form a drug solution with a concentration of 40%; mix the above solution (1 part) with dichloromethane and 1,4-dioxane (9 parts, volume ratio 3:2) under ultrasonic condition (ice bath, 200 W, 4 min) to obtain breviscapine organic gel (see attached Figure 4 k).

[0045] Example 13: Take 5 mg of breviscapine raw material and add a small amount of solvent, mix well by vortex, and observe the system state; if the drug is not completely dissolved, continue to add a small amount of solvent; repeat until the drug is completely dissolved and the system is clear. Record the amount of solvent required and calculate the approximate solubility of breviscapine in the solvent.

[0046] It can be seen that breviscapine is easily soluble in dimethyl sulfoxide, pyridine and N-methyl pyrrolidone, and also has high solubility in N,N-diethylacetamide and N,N-dimethylformamide, which can be used as potential good solvents.

[0047] Combining the examples and comparative examples, it is found that dimethyl sulfoxide has wide adaptability and can make breviscapine form a gel in most cases, and it is low in toxicity, safer, and miscible with most solvents, so it is the preferred good solvent.

[0048] Example 14: As can be seen from Example 1, the concentration of breviscapine in dichloromethane system is 4%, and the gel parameter is that the ratio of the viscosity of the system to the viscosity of the solvent used is 240; the concentration of breviscapine in Example 7 is 2%, and the gel parameter is that the ratio of the viscosity of the system to the viscosity of the solvent used is 13; it can be seen that the 4% gel has better gel performance than the 2% gel; therefore, the preferred concentration of breviscapine in breviscapine organic gel is ≥4%.

[0049] Example 15: Characterization of breviscapine organic gel

[0050] The scutellarein organic gel (4%) obtained in Example 1 and the scutellarein suspensions in Comparative Examples 1 (0.5%), 2 (1%), and 3 (1.75%) were taken in the appropriate amount and tested in a rheometer. The results are shown in Table Figure 2 . The results show that the product obtained in Example 1 does not flow when inverted, and the ratio of the storage modulus (G') to the loss modulus (G") is about 12.5, indicating that a gel is formed.

[0051] The scutellarein organic gel obtained in Example 1 was taken in the appropriate amount, freeze-dried to obtain a dry gel, and ground to pass through a 100-mesh sieve. The powder was scanned using a powder X-ray diffractometer (PXRD) under the following conditions: the scanning angle was 2θ, the step was 0.02°, the scanning speed was 8° / min, and the scanning range was 5-60°. The results are shown in Table Figure 3 A. Figure 3 A shows that the scutellarein raw material shows multiple characteristic peaks, indicating that it is in a crystalline state; however, the characteristic peaks of the gel formed in Example 1 are weakened, and the crystallinity is reduced, indicating that the ordered arrangement of the molecules in the original crystal lattice of scutellarein is disrupted and reassembled to some extent during the self-gelation process.

[0052] The dry gel powder was taken in the appropriate amount, mixed with a small amount of KBr, and pressed into a tablet. The infrared absorption of the sample in the range of 4000-400 cm-1 was determined using a Fourier transform infrared spectrometer. The results are shown in Table Figure 3 B. Figure 3 B shows that, compared with the raw material, the product formed in Example 1 has characteristic peaks at 3380, 2922, 1729, 1602, 1486, 1364, 1252, and 1185 cm-1, and the intensity is reduced, indicating that intermolecular interactions such as potential hydrogen bonding are formed during the self-gelation process.

[0053] Example 16: The in vitro transdermal performance of the scutellarein organic gel obtained in Example 1 and the scutellarein suspension in Comparative Example 6 was determined. A Franz transdermal diffusion apparatus was used, with mouse back skin as the barrier and phosphate buffer (pH = 6.8) as the receiving medium. The drug concentration in the receiving medium was determined by sampling at predetermined time points. The in vitro permeation curve was plotted, and the key parameters such as the permeation rate, cumulative permeation amount, and intradermal retention amount were calculated. The results are shown in Table Figure 6 . The results show that the transdermal performance of the scutellarein organic gel is significantly better than that of the corresponding suspension. Not only can it be quickly absorbed without a lag phase, but also the cumulative skin permeation amount is increased by 2.3 times and the steady-state transdermal rate is increased by 2 times in 12 hours.

[0054] The following experiments were also conducted during the screening process, which are given as comparative examples herein:

[0055] Comparative Example 1: The breviscapine raw material was weighed and added to an appropriate amount of dimethyl sulfoxide to completely dissolve to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with dichloromethane (79 parts) under ultrasonic conditions (ice bath, 600 W, 1 min), and the resulting mixed system failed to form a gel (see Figure 1a). Figure 1 a).

[0056] Comparative Example 2: The breviscapine raw material was weighed and added to an appropriate amount of dimethyl sulfoxide to completely dissolve to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with dichloromethane (39 parts) under ultrasonic conditions (ice bath, 600 W, 1 min), and the resulting mixed system failed to form a gel (see Figure 1b). Figure 1 b).

[0057] Comparative Example 3: The breviscapine raw material was weighed and added to an appropriate amount of dimethyl sulfoxide to completely dissolve to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with dichloromethane (22 parts) under ultrasonic conditions (ice bath, 600 W, 1 min), and the resulting mixed system failed to form a gel (see Figure 1c). Figure 1 c).

[0058] Comparative Example 4: The breviscapine raw material was weighed and added to an appropriate amount of N,N-dimethylformamide to completely dissolve to form a drug solution with a concentration of 10%; the above solution (1 part) was mixed with dichloromethane (1.5 parts) under ultrasonic conditions (ice bath, 600 W, 1 min), and the resulting mixed system failed to form a gel (see Figure 1a). Figure 5 a).

[0059] Comparative Example 5: The breviscapine raw material was weighed and added to an appropriate amount of N,N-diethylacetamide to completely dissolve to form a drug solution with a concentration of 10%; the above solution (1 part) was mixed with dichloromethane (1.5 parts) under ultrasonic conditions (ice bath, 600 W, 1 min), and the resulting mixed system failed to form a gel (see Figure 1b). Figure 5 b).

[0060] Comparative Example 6: The breviscapine raw material was weighed and added to an appropriate amount of dimethyl sulfoxide to completely dissolve to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with dichloromethane (9 parts) under high shear (10000 rpm, 3 min), and the resulting mixed system failed to form a gel (see Figure 1c). Figure 5 c).

[0061] Comparative Example 7: The breviscapine raw material was weighed and added to an appropriate amount of dimethyl sulfoxide to completely dissolve to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with anhydrous ethanol (9 parts) under ultrasonic conditions (ice bath, 600 W, 3 min), and the resulting mixed system failed to form a gel (see Figure 1d). Figure 5 d).

[0062] Comparative Example 8: The breviscapine raw material was weighed and added with appropriate amount of pyridine to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with cyclohexane (9 parts) under ultrasonic condition (ice bath, 300 W, 5 min), and the obtained mixed system failed to form a gel (see Appendix Figure 5 e).

[0063] Comparative Example 9: The breviscapine raw material was weighed and added with appropriate amount of pyridine to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with n-hexane (9 parts) under ultrasonic condition (ice bath, 800 W, 4 min), and the obtained mixed system failed to form a gel (see Appendix Figure 5 f).

[0064] Comparative Example 10: The breviscapine raw material was weighed and added with appropriate amount of pyridine to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with diethyl ether (9 parts) under ultrasonic condition (ice bath, 1000 W, 1 min), and the obtained mixed system failed to form a gel (see Appendix Figure 5 g).

[0065] Comparative Example 11: The breviscapine raw material was weighed and added with appropriate amount of N,N-dimethylformamide to form a drug solution with a concentration of 10%; the above solution (1 part) was mixed with ethyl acetate (1.5 parts) under ultrasonic condition (ice bath, 600 W, 2 min), and the obtained mixed system failed to form a gel (see Appendix Figure 5 h).

[0066] Comparative Example 12: The breviscapine raw material was weighed and added with appropriate amount of dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with acetonitrile (9 parts) under high shear condition (12000 rpm, 2 min), and the obtained mixed system failed to form a gel (see Appendix Figure 5 i).

[0067] Comparative Example 13: The breviscapine raw material was weighed and added with appropriate amount of dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with 1,3-propanediol (9 parts) under ultrasonic condition (ice bath, 1000 W, 1 min), and the obtained mixed system failed to form a gel (see Appendix Figure 5 j).

[0068] Comparative Example 14: The breviscapine raw material was weighed and added with appropriate amount of dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with benzyl alcohol (9 parts) under ultrasonic condition (ice bath, 1000 W, 1 min), and the obtained mixed system failed to form a gel (see Appendix Figure 5 k).

[0069] Comparative Example 15: The breviscapine raw material was weighed and added with dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with triethylene glycol monoethyl ether (9 parts) under ultrasonic condition (ice bath, 800 W, 3 min), and the obtained mixture failed to form a gel (see Appendix Figure 5 l).

[0070] Comparative Example 16: The breviscapine raw material was weighed and added with dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with acetone (9 parts) under ultrasonic condition (ice bath, 700 W, 3 min), and the obtained mixture failed to form a gel (see Appendix Figure 5 m).

[0071] Comparative Example 17: The breviscapine raw material was weighed and added with dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with R-propylene carbonate (9 parts) under ultrasonic condition (ice bath, 700 W, 3 min), and the obtained mixture failed to form a gel (see Appendix Figure 5 n).

[0072] Comparative Example 18: The breviscapine raw material was weighed and added with dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with triethyl phosphate (9 parts) under ultrasonic condition (ice bath, 200 W, 8 min), and the obtained mixture failed to form a gel (see Appendix Figure 5 o).

[0073] Comparative Example 19: The breviscapine raw material was weighed and added with dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with 2-hydroxyethyl acrylate (9 parts) under ultrasonic condition (ice bath, 300 W, 5 min), and the obtained mixture failed to form a gel (see Appendix Figure 5 p).

[0074] Comparative Example 20: The breviscapine raw material was weighed and added with dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with dimethyl phthalate (9 parts) under high shear condition (10000 rpm, 2 min), and the obtained mixture failed to form a gel (see Appendix Figure 5 q).

[0075] Comparative Example 21: The breviscapine raw material was weighed and added with N,N-dimethylformamide to form a drug solution with a concentration of 10%; the above solution (1 part) was mixed with isopropyl myristate (1.5 parts) under high shear condition (12000 rpm, 2 min), and the obtained mixture failed to form a gel (see AppendixFigure 5 r).

[0076] Comparative Example 22: A scutellarein raw material was weighed and added with an appropriate amount of dimethyl sulfoxide to form a drug solution with a concentration of 40%; the above solution (1 part) was mixed with methanol (9 parts) under ultrasonic conditions (ice bath, 600 W, 3 min), and the obtained mixed system failed to form a gel (see the attached gel photograph). Figure 5 s).

[0077] The above merely describes the preferred embodiments of the present application, and it should be noted that the above preferred embodiments should not be regarded as a limitation to the present application, and the protection scope of the present application should be defined by the scope of the claims. For those skilled in the art, several improvements and refinements can be made without departing from the spirit and scope of the present application, and these improvements and refinements should also be regarded as the protection scope of the present application.

Claims

1. A batimastat self-gelling organogel, characterized in that: The gel is composed of breviscapine and organic solvent only, without other gel materials, and the breviscapine serves as both active ingredient and gel factor; the organic solvent is composed of a good solvent and a poor solvent of breviscapine, wherein the good solvent is used in an amount capable of fully dissolving the breviscapine contained in the gel, and the poor solvent is used in an amount capable of fully dispersing the breviscapine solution in the good solvent; The content of breviscapine is greater than or equal to 2% by weight of the gel; The weight ratio of the good solvent to the poor solvent is 1:19-1:7; The poor solvent is one or more of dichloromethane, n-butanol, n-octanol, acetonitrile, glycerol, dioxane and trifluoroacetic acid; The good solvent is one or more of dimethyl sulfoxide, pyridine, N-methyl pyrrolidone, N,N-diethylacetamide and N,N-dimethylformamide; The preparation method is as follows: the gel is prepared by using the anti-solvent precipitation method, i.e. taking breviscapine raw material, adding a good solvent to fully dissolve it, then mixing it with a poor solvent uniformly, and removing or not removing the good solvent, to obtain the gel. The good solvent and the poor solvent are mixed uniformly by using ultrasonic.

2. The bazzinib self-gelling organogel according to claim 1, characterized in that: The content of breviscapine is greater than or equal to 4% by weight of the gel.

3. The bazzinib self-gelling organogel according to claim 1, characterized in that: The poor solvent is one or more of dichloromethane and glycerol.

4. The baccalinum self-gelling organogel according to claim 1, characterized in that: The good solvent is dimethyl sulfoxide.

5. The baccalinum self-gelling organic gel according to claim 1, characterized in that: The system does not flow down in a container, or the ratio of the viscosity of the system to the viscosity of the solvent used is not less than 10, or the ratio of the storage modulus G' to the loss modulus G" of the system in the rheological test is not less than 10.

6. A process for the preparation of a gimatecan self-gelling organogel according to claim 1, characterized by: The gel is prepared by using the anti-solvent precipitation method, i.e. taking breviscapine raw material, adding a good solvent to fully dissolve it, then mixing it with a poor solvent uniformly, and removing or not removing the good solvent, to obtain the gel; wherein the good solvent and the poor solvent are mixed uniformly by using ultrasonic.

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