CN115337318A - Traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis - Google Patents
Traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P37/00—Drugs for immunological or allergic disorders
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Abstract
The invention discloses a traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis, which comprises sinomenine-glycyrrhizic acid self-assembly prepared from sinomenine hydrochloride aqueous solution and glycyrrhizic acid aqueous solution, wherein the molar concentration of the sinomenine hydrochloride aqueous solution is 50-150 mmol/L, the molar concentration of the glycyrrhizic acid aqueous solution is 25-100 mmol/L, and the molar ratio of sinomenine hydrochloride to glycyrrhizic acid in the sinomenine hydrochloride aqueous solution and the glycyrrhizic acid aqueous solution is (1-4): 1. The sinomenine-glycyrrhizic acid self-assembly provided by the invention is simple and green in preparation method, high in safety and good in treatment effect on rheumatoid arthritis.
Description
Technical Field
The invention relates to the technical field of medicines. More specifically, the invention relates to a traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis.
Background
Rheumatoid Arthritis (RA) is a common chronic systemic autoimmune disease that can cause cartilage and bone damage in multiple joints throughout the body, ultimately leading to disability. The global prevalence of RA is about 1%, with women having a higher prevalence than men. In China, RA affects 0.34% -0.36% of population, and because the population cardinality is large in China, the number of RA affected people is about 500 thousands, the remission rate is about 8.6%, the cost of RA patients is high every year, and certain economic and psychological burdens are caused to the patients and the family members of the patients. Age 30-50 is an age group with high incidence of RA, and therefore RA is one of the causes of reduced labor intensity. It follows that RA has become a global health problem. Since the disease is a progressive, invasive, chronic disease, it should be diagnosed early and treated quickly, with appropriate treatment strategies to control the disease progression and reduce the risk of disability.
At present, no treatment means for completely curing RA exists. The current therapeutic goal is to reduce the activity of the disease and minimize joint damage and improve the quality of life of the patient. Clinically, the main therapeutic Drugs for RA include Nonsteroidal Anti-inflammatory Drugs (NSAIDs), corticosteroids, disease-modifying Anti-inflammatory-rheumatic Drugs (DMARDs), biological products, etc., but have many adverse reactions. Wherein NSAIDs increase cardiovascular risk, such as myocardial infarction; chronic corticosteroid use can cause peptic ulcer and pancreatitis; DMARDs not only have slow effect, but also increase the burden of the liver and the kidney; the biological agent is expensive and is easy to cause side effects such as bacterial and fungal infection.
The effective components of the traditional Chinese medicine are main effective components extracted and separated from the traditional Chinese medicine, have been widely researched for a long time by the unique pharmacological activity of the traditional Chinese medicine, are inspired by the pharmacological activity of the traditional Chinese medicine, and are also used for treating various diseases, such as rheumatoid arthritis and the like. Although the effective components of the traditional Chinese medicine are widely applied and accepted in diseases, the clinical application of the effective components of the traditional Chinese medicine is still limited due to the problems of poor solubility of certain medicine molecules, low bioavailability, poor targeting property, toxic and side effects and the like. The nano-drug has attracted great interest as a hot spot in recent years due to its unique properties, such as targeted delivery, controlled release, lower systemic toxicity and higher drug bioavailability. Drug delivery systems such as nanoparticles, nano-micelles, nano-vesicles, nano-fibers, nano-liposomes, and the like have been developed and receive much attention. Although many nano-drug delivery systems have been reported, only a few have been converted to clinical applications, such as amphotericin B. Moreover, most nanocarriers have low drug loading, and some synthetic nanocarriers may cause toxicity and inflammation during degradation and metabolism in the human body. Meanwhile, some inorganic adjuvants cannot be eliminated by human metabolism, such as silicon dioxide, metal ions or skeletons, magnetic nanoparticles and the like. Therefore, it is necessary to develop a natural low-toxicity nano-drug based on the active ingredients of traditional Chinese medicines for clinical use, which not only can increase the solubility of insoluble drugs, improve the bioavailability and enhance the targeting property, but also can achieve the effects of slow release and synergistic effect. Compared with other nano-drug delivery systems, the self-assembly nano-drug is green and simple to synthesize, has high drug loading, and can realize highly stable drug delivery without a carrier. Therefore, natural-derived active ingredient self-assemblies have been widely studied and used.
Caulis sinomenii has long been used for clinical treatment of rheumatoid arthritis, and various traditional Chinese medicine compounds have been developed and show good treatment effects, mainly including: baixianfeng decoction, qingbai Tongbi capsule and Qingbi decoction. Sinomenine is alkaloid monomer extracted from dried rhizome of caulis Sinomenii and caulis Sinomenii of Menispermaceae, and has antiinflammatory and immunity regulating effects. The therapeutic effect of sinomenine on rheumatoid arthritis has been reported early. In order to improve the bioavailability of sinomenine, qiying Shen and the like report that a novel thermosensitive liposome carrying sinomenine hydrochloride is developed by adopting a pH gradient method for treating RA, but the safety and clinical application of the thermosensitive liposome are limited, so that the design of a natural-source active ingredient self-assembly with better safety becomes an urgent problem to be solved.
Disclosure of Invention
An object of the present invention is to solve at least the above problems and to provide at least the advantages described later.
The invention also aims to provide the traditional Chinese medicine micromolecule self-assembly for treating the rheumatoid arthritis, which has the advantages of simple preparation method, greenness, high safety and good treatment effect on the rheumatoid arthritis.
In order to achieve these objects and other advantages in accordance with the present invention, there is provided a traditional Chinese medicine small molecule self-assembly for the treatment of rheumatoid arthritis, comprising a sinomenine-glycyrrhizic acid self-assembly made of a sinomenine hydrochloride aqueous solution and a glycyrrhizic acid aqueous solution, wherein the sinomenine hydrochloride aqueous solution has a molar concentration of 50 to 150mmol/L, the glycyrrhizic acid aqueous solution has a molar concentration of 25 to 100mmol/L, and the sinomenine hydrochloride aqueous solution and the glycyrrhizic acid aqueous solution have a molar ratio of sinomenine hydrochloride to glycyrrhizic acid of (1 to 4): 1.
Preferably, the molar concentration of the sinomenine hydrochloride aqueous solution is 100mmol/L.
Preferably, the molar concentration of the glycyrrhizic acid aqueous solution is 50mmol/L.
Preferably, the molar ratio of sinomenine hydrochloride to glycyrrhizic acid in the sinomenine hydrochloride aqueous solution and the glycyrrhizic acid aqueous solution is 2.
Preferably, the sinomenine-glycyrrhizic acid self-assembly is in a thermally reversible gel state.
Preferably, the preparation method of the sinomenine-glycyrrhizic acid self-assembly comprises the following steps:
step one, dissolving glycyrrhizic acid in water, and heating the glycyrrhizic acid to dissolve at 70-90 ℃ to prepare a glycyrrhizic acid water solution;
step two, dissolving sinomenine hydrochloride in water, and heating to dissolve at 70-90 ℃ to prepare a sinomenine aqueous solution;
mixing the glycyrrhizic acid aqueous solution and the sinomenine aqueous solution, and stirring to form a self-assembly body in a gel state;
and step four, freezing and drying the gel-state self-assembly body to obtain the sinomenine-glycyrrhizic acid self-assembly body.
The invention also provides application of the traditional Chinese medicine micromolecule self-assembly body for treating rheumatoid arthritis in preparation of medicines for treating rheumatoid arthritis.
The invention at least comprises the following beneficial effects: the invention relates to a traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis, which is based on the compatibility of traditional Chinese medicines, and based on the characteristic that the traditional Chinese medicine micromolecules can be self-combined to form the self-assembly under certain conditions, the sinomenine-glycyrrhizic acid self-assembly is prepared by selecting sinomenine-main component of sinomenine and glycyrrhizic acid-main component of glycyrrhizic acid which are widely used clinically, has good treatment effect on the rheumatoid arthritis, can be used for developing new drugs for clinical treatment of the rheumatoid arthritis, and provides a treatment strategy with great prospect for the rheumatoid arthritis; in addition, the preparation process of the self-assembly body mainly adopts a high-temperature method, other reagents are not needed, and the method is simple, green and high in safety.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Drawings
FIG. 1 is a macroscopic image and a scanning electron microscope image of the sinomenine-glycyrrhizic acid self-assembly in the invention after being dissolved in water;
FIG. 2 is a scanning potential diagram of the sinomenine-glycyrrhizic acid self-assembly of the present invention;
FIG. 3 is a UV-VIS absorption spectrum of sinomenine, glycyrrhizic acid, and the sinomenine-glycyrrhizic acid self-assembly according to the present invention;
FIG. 4 is an infrared spectrum of sinomenine, glycyrrhizic acid, and the sinomenine-glycyrrhizic acid self-assembly according to the present invention;
FIG. 5 is a PXRD spectrum of sinomenine, glycyrrhizic acid, and sinomenine-glycyrrhizic acid self-assemblies of the present invention;
FIG. 6 is a graph showing the experimental results of the therapeutic effects on rheumatoid arthritis in mice;
FIG. 7 is a H & E staining chart of mouse ankle tissue sections;
FIG. 8 is a graph of the local pathological status scores of mice;
FIG. 9 is a graph showing the expression of a local anti-tartaric acid phosphatase in a joint;
FIG. 10 is a TRAP expression statistical analysis chart.
Detailed Description
The present invention is described in further detail below with reference to the drawings and the detailed description so that those skilled in the art can implement the invention with reference to the description.
It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or combinations thereof.
It is to be noted that the experimental methods described in the following embodiments are all conventional methods unless otherwise specified, and the reagents and materials, if not otherwise specified, are commercially available; in the description of the present invention, it should be noted that unless otherwise explicitly stated or limited, the terms "mounted," "connected," and "disposed" are to be construed broadly and can, for example, be fixedly connected, disposed, detachably connected, disposed, or integrally connected and disposed. The specific meanings of the above terms in the present invention can be understood in a specific case to those of ordinary skill in the art. The terms "transverse," "longitudinal," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," and the like are used in an orientation or positional relationship indicated in the drawings for convenience in describing the invention and to simplify the description, and are not intended to indicate or imply that the device or element so referred to must have a particular orientation, be constructed in a particular orientation, and be constructed in operation, and are not to be construed as limiting the invention.
The invention provides a traditional Chinese medicine small molecule self-assembly for treating rheumatoid arthritis, which comprises a sinomenine-glycyrrhizic acid self-assembly prepared from sinomenine hydrochloride aqueous solution and glycyrrhizic acid aqueous solution, wherein the molar concentration of the sinomenine hydrochloride aqueous solution is 50-150 mmol/L, the molar concentration of the glycyrrhizic acid aqueous solution is 25-100 mmol/L, and the molar ratio of sinomenine hydrochloride aqueous solution to glycyrrhizic acid in the glycyrrhizic acid aqueous solution is (1-4): 1.
In one embodiment, the molar concentration of the sinomenine hydrochloride aqueous solution is 100mmol/L.
In one embodiment, the glycyrrhizic acid aqueous solution has a molar concentration of 50mmol/L.
In one embodiment, the molar ratio of sinomenine hydrochloride to glycyrrhizic acid in the sinomenine hydrochloride aqueous solution and the glycyrrhizic acid aqueous solution is 2.
In one embodiment, the sinomenine-glycyrrhizic acid self-assembly is in a thermally reversible gel state.
In one embodiment, the preparation method of the sinomenine-glycyrrhizic acid self-assembly comprises the following steps:
step one, dissolving glycyrrhizic acid in water, and heating to dissolve the glycyrrhizic acid at 70-90 ℃ to prepare glycyrrhizic acid water solution;
step two, dissolving sinomenine hydrochloride in water, and heating to dissolve at 70-90 ℃ to prepare a sinomenine aqueous solution;
mixing the glycyrrhizic acid aqueous solution and the sinomenine aqueous solution, and stirring to form a self-assembly body in a gel state;
and step four, freezing and drying the gel-state self-assembly body to obtain the sinomenine-glycyrrhizic acid self-assembly body.
The invention also provides application of the traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis in preparing a medicine for treating rheumatoid arthritis.
It is to be noted that the experimental methods described in the following embodiments are all conventional methods unless otherwise specified, and the reagents and materials are commercially available unless otherwise specified.
< example 1>
A traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis is prepared by the following steps: taking sinomenine hydrochloride aqueous solution with the concentration of 100mmol/L and glycyrrhizic acid aqueous solution with the concentration of 50mmol/L, and mixing the two solutions according to the mol ratio of 2:1, and preparing the sinomenine-glycyrrhizic acid self-assembly.
< example 2>
A traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis is prepared by the following steps:
step one, dissolving glycyrrhizic acid in water, heating to dissolve at 80 ℃ to prepare glycyrrhizic acid water solution with the concentration of 50 mmol/L;
step two, dissolving sinomenine hydrochloride in water, and heating to dissolve at 80 ℃ to prepare a sinomenine aqueous solution with the concentration of 100 mmol/L;
taking a glycyrrhizic acid water solution and a sinomenine water solution, and mixing the sinomenine hydrochloride and the glycyrrhizic acid according to a molar ratio of 2:1, and stirring to form a self-assembly body in a gel state;
and step four, freezing and drying the gel-state self-assembly body to obtain the sinomenine-glycyrrhizic acid self-assembly body.
< comparative example 1>
A Chinese medicinal composition for treating rheumatoid arthritis comprises sinomenine.
< comparative example 2>
A Chinese medicinal composition for treating rheumatoid arthritis comprises glycyrrhizic acid.
< comparative example 3>
A traditional Chinese medicine mixture for treating rheumatoid arthritis comprises the following components in a molar ratio of 2:1 of sinomenine and glycyrrhizic acid mixture.
< comparative example 4>
A Chinese medicinal small molecule mixture for treating rheumatoid arthritis comprises methotrexate as positive drug.
< morphological characterization of self-assembled body >
FIG. 1 is a macroscopic image (A) and a scanning electron microscope (B) of the sinomenine-glycyrrhizic acid self-assemblies prepared in examples 1 and 2 after being dissolved in water, the macroscopic image showing a hydrogel state having a thermoreversible property; the scanning electron microscope image shows that the nano-fiber has the shape of fiber in the micro-scale, and has good nano-property and stability.
< analysis of potential of self-assembled body >
Fig. 2 is a scanning potential diagram of the sinomenine-glycyrrhizic acid self-assembly prepared in examples 1 and 2, and it can be seen from fig. 2 that the Zeta potential of the sinomenine-glycyrrhizic acid self-assembly is-39.7 mV, which indicates that the sinomenine-glycyrrhizic acid self-assembly has good stability and can be stably stored at room temperature.
< UV-visible absorption Spectroscopy test of self-assembled body >
Taking the sinomenine-glycyrrhizic acid self-assembly (SIN-GA), sinomenine (SIN) and Glycyrrhizic Acid (GA) in the example 2, the comparative example 1 and the comparative example 2, carrying out ultraviolet-visible absorption spectrum test for primarily judging whether the sinomenine and the glycyrrhizic acid are assembled, wherein a spectrogram is shown in figure 3, and as can be seen from the figure, the maximum absorption wavelength of the glycyrrhizic acid is mainly formed by conjugation of a triterpene saponin mother nucleus, and after the sinomenine is assembled, the absorption wavelength changes and is shifted to 260nm from 256nm to a long wave direction, so that the interaction between the sinomenine and the glycyrrhizic acid is shown, and the formation of the assembly is confirmed.
< Infrared Spectrum measurement of self-assembled body >
Infrared spectroscopic measurements were performed on the sinomenine-glycyrrhizic acid self-assemblies (SIN-GA), sinomenine (SIN), glycyrrhizic Acid (GA) in example 2, comparative example 1, and comparative example 2 to further determine the binding sites for sinomenine and glycyrrhizic acid self-assembly. FTIR spectra of SIN, GA and SIN-GA are shown in FIG. 4. 1715cm -1 Is a stretching vibration characteristic peak of carbonyl (C = O) on GA glucuronic acid carboxyl, and after SIN self-assembles, the peak moves to 1690cm in low wave number -1 The change of GA wave number in infrared spectrogram may be caused by electrostatic phase generated by carboxyl on GA glucuronic acid carbonyl and SIN quaternary ammonium nitrogen atomInteraction, which results in delocalization of the double bond electrons on the carbonyl group and a decrease in electron cloud density, leading to a weakening of the bond energy and a decrease in the stretching vibration frequency.
< PXRD test of self-Assembly >
PXRD tests were performed on the sinomenine-glycyrrhizic acid self-assembly (SIN-GA), sinomenine (SIN), glycyrrhizic Acid (GA) in example 2, comparative example 1, and comparative example 2, and the results are shown in fig. 5. The map of SIN in the figure shows a sharp peak 2 theta =8.986 °
2θ＝12.241°
2θ＝13.038°
2θ＝13.570°
And when more than 20 diffraction single peaks are obtained, the ordered structure sequence is shown, and the crystal property is consistent with the literature report; GA atlas at 2 theta =14.167 °
The position diffraction broad peak proves that GA does not have crystal property; SIN-GA 2 theta =14.107 °
And a diffraction broad peak with a little difference with the GA peak position appears, which indicates that the materials are all amorphous before and after assembly and show an amorphous intermolecular arrangement mode.
< test on therapeutic Effect of rheumatoid arthritis >
An adjuvant-induced arthritis (AA) mouse model was selected, and each of the components in example 2 and comparative examples 1 to 4 and methotrexate, which is a positive drug, were taken, and the mice were divided into a Control group (blank Control group), an AA (AA model group), an SIN (sinomenine-administered group), a GA (glycyrrhizic acid-administered group), an SIN-GA (sinomenine-glycyrrhizic acid self-assembly-administered group), an S + G (sinomenine, glycyrrhizic acid mixed-administered group), and an MTX (methotrexate-administered group), which were groups, and subjected to comparative tests. FIG. 6A is a schematic time period chart of the whole animal experiment; b is appearance expression diagram of ankle joint of each group of mice on day 31; c is the dynamic change of the joint diameter of each group of mice in the experimental process, the ankle joint diameter of the mice is measured once every 3 days, and n =10; d is dynamic change of ankle joint scores of all groups of mice in the whole experiment process, the ankle joint swelling degree of the mice is scored every 3 days, and n =10; e is the level of the splenic index of each group of mice after the end of the experiment, n =10.
In fig. 6, a can see that the whole test period is: after the SPF grade C57BL/6N mouse is adaptively fed for one week in an animal room, the construction of an AA model is started on the 0 th day, different administration interventions are given according to experimental requirements on the 4 th day, and the ankle joint diameter is measured and scored once every 3 days; 28 days after the dosing intervention, the mice were sacrificed by cervical dislocation, samples were collected and the experiment was ended. In FIG. 6, B shows that the ankle joint of the Control group mice appeared normal and were not restricted in movement; the ankle joint swelling of the AA group mice is obvious and involves toes, and the movement of the mice presents the typical limited characteristic of three-foot lameness; after SIN-GA intervention, the ankle joint swelling degree of the mice is obviously reduced, the activity limitation condition is relieved, and the joint performance and the activity characteristics similar to those of methotrexate administration group (MTX) mice are shown; the mice of the sinomenine administration group (SIN) and the glycyrrhizic acid administration Group (GA) have no obvious difference with the mice of the AA group. C and D in fig. 6 show that the ankle diameter of the AA group mice was significantly increased (P < 0.01) relative to the Control group mice and peaked (4.0-4.5 mm) on day 16, and the joint score of the mice remained at a level of 4 points; after SIN-GA intervention, the ankle joint diameter of a mouse is remarkably reduced to about 3.5mm (P < 0.01), the joint score is reduced to 2 points or even 1 point (P < 0.01), the activity state of the mouse is also remarkably improved, and the SIN-GA shows a similar relieving effect to methotrexate; the diameter and the score of the joints of mice of the sinomenine and glycyrrhizic acid mixed administration group (S + G) are reduced, but have no statistical significance (P > 0.05); while the joint diameter and joint score of the SIN and GA group mice were not significantly changed compared to the AA group.
< test on local pathological State of ankle Joint in mouse >
Ankle joints of each group of mice in the rheumatoid arthritis treatment effect test are collected, and paraffin sections are prepared after fixation and decalcification. Ankle tissue sections from each group of mice were H & E stained, and the results are shown in fig. 7, and the local pathological state was scored, as shown in fig. 8. The results showed that the AA group showed typical local joint pathology states such as massive infiltration of inflammatory cells, synovial cell proliferation, cartilage damage and bone erosion, etc., and an increase in ankle pathology score (P < 0.01) compared to the Control group; after SIN-GA trunk prognosis, the pathological state of ankle joints of mice is obviously improved, inflammatory cell infiltration is reduced, cartilage damage is improved, and the pathological score of ankle joints is obviously reduced (P is less than 0.01); the same improvement in the pathological state of the joints can be observed in the MTX group; the local ankle pathological state of the mice of the SIN, GA and S + G groups was not significantly improved.
Osteoclasts are the major bone-resorbing cells in an organism and are critical to maintaining homeostasis of bone tissue. To analyze the activity of mouse ankle local osteoclasts, we analyzed the expression of a local anti-Tartrate Acid Phosphatase (TRAP) in the joints, as shown in fig. 9, and statistically analyzed the expression of the TRAP, as shown in fig. 10. The results show that the expression of local TRAP of ankle joints of AA group mice is obviously increased (P < 0.01); the SIN-GA and MTX intervention can obviously inhibit the expression of local TRAP of joints (P < 0.01), which indicates that the SIN-GA can obviously inhibit the activity of local osteoclasts of ankle joints; while SIN, GA and S + G had no significant effect on TRAP expression.
In conclusion, under the same administration dosage, the sinomenine-glycyrrhizic acid self-assembly body shows better treatment effect than single medicine and direct mixed administration, and the effect is similar to that of positive medicine methotrexate.
The number of apparatuses and the scale of the process described herein are intended to simplify the description of the present invention. Applications, modifications and variations of the present invention will be apparent to those skilled in the art.
While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable to various fields of endeavor for which the invention may be embodied with additional modifications as would be readily apparent to those skilled in the art, and the invention is therefore not limited to the details shown and described herein without departing from the generic concept as defined by the claims and their equivalents.
Claims (7)
1. The traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis is characterized by comprising sinomenine-glycyrrhizic acid self-assembly prepared from sinomenine hydrochloride aqueous solution and glycyrrhizic acid aqueous solution, wherein the molar concentration of the sinomenine hydrochloride aqueous solution is 50-150 mmol/L, the molar concentration of the glycyrrhizic acid aqueous solution is 25-100 mmol/L, and the molar ratio of sinomenine hydrochloride to glycyrrhizic acid in the sinomenine hydrochloride aqueous solution and the glycyrrhizic acid aqueous solution is (1-4): 1.
2. The traditional Chinese medicine small molecule self-assembly for treating rheumatoid arthritis according to claim 1, wherein the molar concentration of the sinomenine hydrochloride aqueous solution is 100mmol/L.
3. The small molecule self-assembly of claim 1, wherein the glycyrrhizic acid aqueous solution has a molarity of 50mmol/L.
4. The traditional Chinese medicine small molecule self-assembly for treating rheumatoid arthritis according to claim 1, wherein the molar ratio of sinomenine hydrochloride to glycyrrhizic acid in the sinomenine hydrochloride aqueous solution and the glycyrrhizic acid aqueous solution is 2.
5. The traditional Chinese medicine small molecule self-assembly for treating rheumatoid arthritis according to claim 1, wherein the sinomenine-glycyrrhizic acid self-assembly is in a thermally reversible gel state.
6. The traditional Chinese medicine small molecule self-assembly for treating rheumatoid arthritis according to claim 1, wherein the preparation method of the sinomenine-glycyrrhizic acid self-assembly comprises the following steps:
step one, dissolving glycyrrhizic acid in water, and heating to dissolve the glycyrrhizic acid at 70-90 ℃ to prepare glycyrrhizic acid water solution;
step two, dissolving sinomenine hydrochloride in water, and heating to dissolve at 70-90 ℃ to prepare a sinomenine aqueous solution;
step three, mixing the glycyrrhizic acid aqueous solution and the sinomenine aqueous solution, and stirring to form a self-assembly body in a gel state;
and step four, freezing and drying the gel-state self-assembly body to obtain the sinomenine-glycyrrhizic acid self-assembly body.
7. Use of the small molecule self-assembly of any one of claims 1 to 6 for the preparation of a medicament for the treatment of rheumatoid arthritis.
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| CN101919913A (en) * | 2010-07-29 | 2010-12-22 | 宁波立华制药有限公司 | Composition with effect of treating rheumatoid arthritis |
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