Traditional Chinese medicine composition for clearing vision and removing nebula and application thereof

Abstract

The application provides a traditional Chinese medicine composition for clearing vision and removing nebula and application thereof, and includes bear bile powder and borneol with a mass ratio of 1-5:1; the bear bile powder includes tauroursodeoxycholic acid and tauroursodeoxycholic acid arginine salt with a molar ratio of 0.4-0.9:0.1-0.6. The application converts tauroursodeoxycholic acid in bear bile powder into tauroursodeoxycholic acid arginine salt, so that the molar ratio of tauroursodeoxycholic acid and tauroursodeoxycholic acid arginine salt in bear bile powder is 0.4-0.9:0.1-0.6, and the bear bile powder is compounded with borneol to treat cataract. Experimental results show that when the molar ratio of tauroursodeoxycholic acid and tauroursodeoxycholic acid arginine salt in bear bile powder is 0.4-0.9:0.1-0.6, the effect of the bear bile powder compounded with borneol in treating cataract is significantly better than that of bear bile powder containing only tauroursodeoxycholic acid or bear bile powder containing only tauroursodeoxycholic acid arginine salt, for example, there is a significant difference in slowing down the degree and thickness of lens turbidity.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a traditional Chinese medicine composition for improving eyesight and clearing away corneal opacity, and its application. Background Technology

[0002] Cataracts are a disease that causes visual impairment due to clouding of the lens of the eye caused by various reasons. Early symptoms are usually not obvious, with only mild blurred vision. In the middle stage, the clouding of the lens gradually worsens, and the degree of blurred vision also increases. Abnormal sensations such as double strabismus, myopia, and glare may also occur. As the disease progresses, the patient may eventually become completely blind.

[0003] Treatment methods for cataracts generally include drug therapy and surgical treatment. Compared with surgical treatment, drug therapy has advantages such as being non-invasive, less expensive, and suitable for all stages of cataract progression. Existing technologies disclose a variety of drugs with preventive or therapeutic effects on cataracts. For example, Chinese patent CN101390943B discloses a traditional Chinese medicine preparation for improving vision, clearing corneal opacity, calming the mind, and clearing heat and nourishing the liver. It is made from pearl powder, zinc gluconate, and Buddleja officinalis, and can reduce the level of malondialdehyde (MDA) in the serum of rats with cataracts, thus being considered to have therapeutic effects on cataracts. Summary of the Invention

[0004] In view of this, the technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition for improving eyesight and clearing away cataracts and its application. The traditional Chinese medicine composition provided in this application can be used to treat cataracts and has significant effects.

[0005] This application provides a traditional Chinese medicine composition for improving eyesight and clearing away corneal opacity, comprising bear bile powder and borneol in a mass ratio of 1 to 5:1;

[0006] The bear bile powder comprises taurine and taurine arginine salt in a molar ratio of 0.4-0.9:0.1-0.6.

[0007] In some specific implementations, the bear bile powder includes tauride-deoxycholic acid and tauride-deoxycholic acid arginine salt in a molar ratio of 1:0.3~0.5.

[0008] In some specific implementations, the taurideoxycholic acid includes one or more of taurideurideoxycholic acid or tauridechenodeoxycholic acid.

[0009] The taurideoxycholic acid arginine salt includes one or more of taurideoxycholic acid arginine salt or taurideoxycholic acid arginine salt.

[0010] In some specific implementations, the bear bile powder is prepared according to the following method:

[0011] a) Dissolve the crude bear bile powder in water, add ethanol, heat under reflux, and filter to obtain a crude bear bile powder solution;

[0012] b) After adjusting the pH of the crude bear bile powder solution to 6-7.5, mix it with arginine and react to obtain a reaction solution. The amount of arginine used is 10 mol% to 60 mol% of taurideoxycholic acid in the crude bear bile powder solution.

[0013] c) The reaction solution is filtered and purified to obtain bear bile powder.

[0014] In some specific implementations, step a) specifically includes:

[0015] After dissolving the crude bear bile powder in water, ethanol is added to achieve an alcohol content of 40% to 60%. The mixture is heated under reflux for 30 to 90 minutes, and the resulting solution is filtered to obtain a crude bear bile powder solution.

[0016] In some specific implementations, step b) specifically refers to:

[0017] The pH of the crude bear bile powder solution was adjusted to 6.5-7.0, arginine was added, and the mixture was stirred at 40℃-50℃ for 2-3 hours. The reaction solution was then obtained by filtration.

[0018] In some specific implementations, step c) specifically includes:

[0019] The reaction solution was filtered, mixed with ethyl acetate, and allowed to stand to obtain a layered mixed solution.

[0020] The lower layer of the mixed solution is mixed with ethanol, stirred, allowed to stand, filtered, and the resulting filtrate is concentrated under reduced pressure to obtain bear bile powder.

[0021] In some specific implementations, a typical preparation process for the bear bile powder is as follows:

[0022] (1) Take the crude bear bile powder, dissolve it in an appropriate amount of water (10 times the amount), add an appropriate amount of ethanol to make the alcohol content reach 50%, heat under reflux (1 hour), filter, and recover the ethanol until there is no alcohol taste, and set aside for later use.

[0023] (2) Adjust the pH of the above-mentioned crude bear bile powder solution to 6.8 using a suitable solution (hydrochloric acid or sodium hydroxide aqueous solution);

[0024] (3) After mixing with arginine, the temperature is raised to 50°C and the mixture is stirred for 3 hours to obtain the reaction solution.

[0025] (4) Filter the above reaction solution, mix the obtained filtrate with 1.5 times the amount of ethyl acetate and let it stand for 2 hours. After separation, mix the lower layer with 4 times the volume of ethanol, stir for 1 hour, let it stand for 3 hours and then filter. Concentrate the obtained filtrate and dry it to obtain bear bile powder.

[0026] In some specific implementations, the borneol is natural borneol.

[0027] This application also provides the use of the traditional Chinese medicine composition described in the above technical solution in the preparation of drugs for treating cataracts.

[0028] In some specific implementations, the cataract is an adhesive cataract, a complicated cataract, a traumatic cataract, or a metabolic cataract.

[0029] This application processes crude bear bile powder, converting some of the taurodeoxycholic acid into taurodeoxycholic acid arginine salt, resulting in a molar ratio of taurodeoxycholic acid to taurodeoxycholic acid arginine salt of 0.4–0.9:0.1–0.6. This mixture is then combined with borneol for the treatment of cataracts. Experimental results show that when the molar ratio of taurodeoxycholic acid to taurodeoxycholic acid arginine salt in bear bile powder is 0.4–0.9:0.1–0.6, the effect of combining it with borneol in treating cataracts is significantly better than when the bear bile powder contains only taurodeoxycholic acid or only taurodeoxycholic acid arginine salt, for example, showing significant differences in reducing the degree and thickness of lens opacity. Attached Figure Description

[0030] Figure 1 This is the high-performance liquid chromatogram of the reference standard;

[0031] Figure 2 This is the high-performance liquid chromatogram of the test sample. Detailed Implementation

[0032] This invention provides a traditional Chinese medicine composition for improving eyesight and clearing corneal opacity, and its application. Those skilled in the art can refer to the content of this document and appropriately modify the process parameters to achieve the desired result. The method and application of this invention have been described through preferred embodiments. Those skilled in the art can obviously make modifications or appropriate alterations and combinations to the method and application described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0033] This application provides a traditional Chinese medicine composition for improving eyesight and clearing away corneal opacity, comprising bear bile powder and borneol in a mass ratio of 1 to 5:1; preferably comprising bear bile powder and borneol in a mass ratio of 3:1;

[0034] The bear bile powder comprises taurine and taurine arginine salt in a molar ratio of 0.4-0.9:0.1-0.6.

[0035] This application processes crude bear bile powder to convert taurodeoxycholic acid into taurodeoxycholic acid arginine salt, resulting in a molar ratio of taurodeoxycholic acid to taurodeoxycholic acid arginine salt of 0.4–0.9:0.1–0.6. This mixture is then combined with borneol for the treatment of cataracts. Experimental results show that when the molar ratio of taurodeoxycholic acid to taurodeoxycholic acid arginine salt in bear bile powder is 0.4–0.9:0.1–0.6, the effect of combining it with borneol in treating cataracts is significantly better than when the bear bile powder contains only taurodeoxycholic acid or only taurodeoxycholic acid arginine salt, for example, showing significant differences in reducing the degree and thickness of lens opacity.

[0036] The following examples further illustrate the traditional Chinese medicine composition provided in this application and its application.

[0037] In the following embodiments, the crude bear bile powder is a commercially available product with a tauroursodeoxycholic acid content of 35.7%.

[0038] Example 1

[0039] a) Mix 9.009 kg of bear bile crude powder with 10 times its volume of water, stir to dissolve, then add ethanol to make the alcohol content of the solution system reach 50%, heat under reflux for 1 hour, filter, and recover ethanol until there is no alcohol odor to obtain bear bile crude powder solution.

[0040] b) Adjust the pH of the crude bear bile powder solution to 6.8, mix it with arginine, heat it to 50°C, and react it for 3 hours with stirring to obtain a reaction solution. The amount of arginine used is 15% of the molar amount of tauroursodeoxycholic acid in the crude bear bile powder solution.

[0041] c) Filter the reaction solution, mix the filtrate with 1.5 times the volume of ethyl acetate, let stand for 2 hours, separate the layers, mix the lower layer with 4 times the volume of ethanol, stir for 1 hour, let stand for 3 hours, filter, concentrate the filtrate under reduced pressure to obtain bear bile powder.

[0042] The bear bile powder obtained in step a) was detected by high performance liquid chromatography under the following conditions:

[0043] Chromatographic conditions and system suitability test: Octadecyl-bonded silica gel was used as the packing material; methanol-sodium dihydrogen phosphate solution (0.03 mol / L) (65:30) was used as the mobile phase, and the pH was adjusted to 4.4 with phosphoric acid; the detection wavelength was 210 nm. The theoretical plate number, calculated based on the tauroursodeoxycholic acid peak, should not be less than 1500.

[0044] Preparation of reference solution: Take an appropriate amount of tauroursodeoxycholic acid reference standard, accurately weigh it, dissolve it in methanol and dilute it quantitatively to prepare a solution containing 1 mg per 1 mL.

[0045] Preparation of test solution: Accurately weigh approximately 50 mg of this product and place it in a 10 mL volumetric flask. Dissolve and dilute to the mark with methanol, shake well, filter, discard the initial filtrate, and collect the subsequent filtrate as the test solution. Accurately pipette 10 μL each of the reference solution and the test solution and inject them into the liquid chromatograph. Perform the determination under the conditions described above.

[0046] See results Figure 1 and Figure 2 , Figure 1 This is the high-performance liquid chromatogram of the reference standard. Figure 2 The high performance liquid chromatogram of the test sample was used, and the content of tauroursodeoxycholic acid in the bear bile powder was calculated to be 37.5% using the external standard method.

[0047] The content of tauroursodeoxycholic acid in the bear bile powder obtained in step c) as described above was 65.2%; the content of arginine in the bear bile powder obtained in step c) was 2.7% as determined by an amino acid analyzer; and the molar ratio of tauroursodeoxycholic acid arginine salt to tauroursodeoxycholic acid was calculated to be 12:88.

[0048] Example 2

[0049] The difference from Example 1 is that, in step b), the amount of arginine used is 60% of the molar amount of tauroursodeoxycholic acid in the crude bear bile powder solution; and the molar ratio of tauroursodeoxycholic acid arginine salt to tauroursodeoxycholic acid in the obtained bear bile powder is 55:45.

[0050] Example 3

[0051] The difference from Example 1 is that, in step b), the amount of arginine used is 30% of the molar amount of tauroursodeoxycholic acid in the crude bear bile powder solution; the molar ratio of tauroursodeoxycholic acid arginine salt to tauroursodeoxycholic acid in the obtained bear bile powder is 27:73.

[0052] Comparative Example 1

[0053] The difference from Example 1 is that in step b), the amount of arginine used is 200% of the molar amount of tauroursodeoxycholic acid in the crude bear bile powder solution, and in the resulting bear bile powder, tauroursodeoxycholic acid is almost entirely converted into tauroursodeoxycholic acid arginine salt.

[0054] Example 4

[0055] The composition was prepared according to the formulation shown in Table 1, and the preparation method is as follows:

[0056] The bear bile powder prepared in Example 1 was dissolved in water to obtain an aqueous solution of bear bile powder; natural borneol was dissolved in the aqueous solution to obtain an aqueous solution of borneol; the aqueous solution of bear bile powder and the aqueous solution of borneol were mixed and water was added to 100% to obtain a composition.

[0057] Table 1. Composition formulations provided in the examples and comparative examples

[0058]

[0059] Example 5

[0060] The difference from Example 4 is that the bear bile powder prepared in Example 2 was used.

[0061] Example 6

[0062] The difference from Example 4 is that the bear bile powder prepared in Example 3 was used.

[0063] Comparative Example 2

[0064] The difference from Example 4 is that the bear bile powder prepared in Comparative Example 1 was used.

[0065] Comparative Example 3

[0066] The difference from Example 4 is that untreated bear bile powder was used.

[0067] The therapeutic effect of the experimental composition on galactose-induced cataract mice.

[0068] (a) Experimental grouping

[0069] Establishment of the mouse model: C57BL / 6 mice were randomly divided into 7 groups of 10 mice each. The treatment methods for each group were as follows:

[0070] Blank control group: fed normally without any additional treatment.

[0071] Galactose group: Galactose treatment only.

[0072] Example 4 group: While undergoing galactose treatment, the composition prepared in Example 4 was injected intraperitoneally twice daily at a dose of 5 mg bear bile powder / kg each time.

[0073] Example 5 group: While undergoing galactose treatment, the composition prepared in Example 5 was injected intraperitoneally twice daily at a dose of 5 mg bear bile powder / kg each time.

[0074] Example 6 group: While undergoing galactose treatment, the composition prepared in Example 6 was injected intraperitoneally twice daily at a dose of 5 mg bear bile powder / kg each time.

[0075] Comparative Example 2: While undergoing galactose treatment, the composition prepared in Comparative Example 2 was injected intraperitoneally twice daily at a dose of 5 mg bear bile powder / kg each time.

[0076] Comparative Example 3: While undergoing galactose treatment, the composition prepared in Comparative Example 3 was injected intraperitoneally twice daily at a dose of 5 mg bear bile powder / kg each time.

[0077] Specific procedures for galactose treatment: Except for the blank control group, all other groups were subcutaneously injected with 60% galactose solution at a dose of 200 mg / kg twice a day for 8 consecutive weeks to induce cataract formation.

[0078] Drug composition treatment: Starting from day 1 of the experiment, except for the control group and the galactose group, the mice in the other groups were injected intraperitoneally with the corresponding drugs daily for 8 weeks.

[0079] (II) Result Detection

[0080] 1. Assessment of lens opacity (cataract grading)

[0081] The mouse lens was examined weekly using a slit-lamp microscope, and its transparency was scored. The scoring criteria are shown in Table 2.

[0082] Table 2 Scoring Criteria

[0083]

[0084] The results are shown in Table 3, which presents the results of lens opacity detection in each group of mice after 8 weeks of treatment.

[0085] Table 3. Results of lens opacity detection in mice after 8 weeks of treatment.

[0086]

[0087] As shown in Table 3, the degree of lens opacity in mice in the galactose group gradually worsened over time, and obvious cataract formation (grade 3-4) was observed by week 4. In Example 4, Example 5, and Example 6, the progression of lens opacity was significantly slowed down due to the protective effect of the drug, and the degree of opacity remained at grade 0-1. In Comparative Example 2, the progression of lens opacity was not controlled, and the degree of opacity remained at grade 3-4. In Comparative Example 3, although the progression of lens opacity was controlled to some extent, the degree of opacity still remained at grade 2-3.

[0088] 2. Lens thickness measurement

[0089] The thickness of the lens in each group of mice was measured using ophthalmic ultrasound to assess changes in lens morphology during cataract formation. Stepper motor-driven OCT can accurately measure the thickness of various structures within the eye of live mice, including the lens thickness. Increased lens thickness is typically accompanied by lens fibrosis and degeneration. The results after 8 weeks of treatment are shown in Table 4, which compares the lens thickness in each group of mice.

[0090] Table 4 Comparison of lens thickness in mice of different groups

[0091]

[0092] As shown in Table 4, the galactose group showed the most significant increase in lens thickness in mice. Comparative group 2 did not effectively reduce the trend of increasing lens thickness in mice. Comparative group 3 had a slight inhibitory effect on the increase in lens thickness in mice. However, the treatments in groups 4, 5, and 6 of Examples significantly slowed down the increase in lens thickness in mice, making it only slightly higher than the blank control group.

[0093] Comparative Example 4

[0094] a) Mix 9.028 kg of bear bile crude powder with 10 times its volume of water, stir to dissolve, and then heat under reflux for 1 hour without adding ethanol, and then filter to obtain a bear bile crude powder solution.

[0095] b) Adjust the pH of the crude bear bile powder solution to 6.8, without adding arginine, heat to 50°C, and stir for 3 hours;

[0096] c) Filter the above solution, mix the filtrate with 1.5 times the volume of ethyl acetate, let stand for 2 hours, after separation, mix the lower layer solution with 4 times the volume of ethanol, stir for 1 hour, let stand for 3 hours, filter, concentrate the filtrate under reduced pressure to obtain 7.384 kg of bear bile crude powder.

[0097] The crude bear bile powder was tested, and the content of tauroursodeoxycholic acid was 36.5%.

[0098] Comparative Example 5

[0099] The pH of 9.009 kg of bear bile crude powder prepared in Comparative Example 4 (step a) was adjusted to 6.8, mixed with 3.104 kg of arginine, and then heated to 50°C and reacted for 3 h with stirring to obtain the reaction solution.

[0100] The reaction solution was filtered, and the filtrate was mixed with 1.5 times the volume of ethyl acetate and allowed to stand for 2 hours. After separation, the lower layer was mixed with 4 times the volume of ethanol, stirred for 1 hour, allowed to stand for 3 hours, and then filtered. The filtrate was concentrated under reduced pressure to obtain 10.195 kg of bear bile powder.

[0101] Example 7

[0102] 9.009 kg of bear bile crude powder prepared in Example 1 (step a) was adjusted to pH 6.8, mixed with 3.108 kg of arginine, and heated to 50°C. The mixture was stirred for 3 h to obtain a reaction solution. The reaction solution was filtered, and the filtrate was mixed with 1.5 times the volume of ethyl acetate and allowed to stand for 2 h. After separation, the lower layer was mixed with 4 times the volume of ethanol, stirred for 1 h, allowed to stand for 3 h, and then filtered. The filtrate was concentrated under reduced pressure to obtain 10.287 kg of bear bile powder.

[0103] Compared with Comparative Examples 4 and 5, this application uses ethanol and water to treat the crude bear bile powder before reacting it with arginine, resulting in a higher yield of bear bile powder.

[0104] The above are merely preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for improving eyesight and clearing away corneal opacity, characterized in that, It consists of bear bile powder and borneol in a mass ratio of 1 to 5:1; The bear bile powder is composed of taurine and taurine arginine salt in a molar ratio of 0.4-0.9:0.1-0.

6.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The bear bile powder is composed of taurine and taurine arginine salt in a molar ratio of 1:0.3~0.

5.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The taurideoxycholic acid is one or more of taurideurideoxycholic acid or tauridecheodeoxycholic acid. The taurideoxycholic acid arginine salt is one or more of tauride-ursodeoxycholic acid arginine salt or tauride-chenodeoxycholic acid arginine salt.

4. The traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The bear bile powder is prepared according to the following method: a) Dissolve the crude bear bile powder in water, add ethanol, heat under reflux, and filter to obtain a crude bear bile powder solution; b) After adjusting the pH of the crude bear bile powder solution to 6-7.5, mix it with arginine and react to obtain a reaction solution. The amount of arginine used is 10 mol%-60 mol% of taurideoxycholic acid in the crude bear bile powder solution. c) The reaction solution is filtered and purified to obtain bear bile powder.

5. The traditional Chinese medicine composition according to claim 4, characterized in that, Step a) specifically includes: After dissolving the crude bear bile powder in water, ethanol is added to achieve an alcohol content of 40% to 60%. The mixture is heated under reflux for 30 to 90 minutes, and the resulting solution is filtered to obtain a crude bear bile powder solution.

6. The traditional Chinese medicine composition according to claim 4, characterized in that, Step b) specifically involves: The pH of the crude bear bile powder solution was adjusted to 6.5-7.0, arginine was added, and the mixture was stirred at 40℃-50℃ for 2-3 hours. The reaction solution was then obtained by filtration.

7. The traditional Chinese medicine composition according to claim 4, characterized in that, Step c) specifically involves: The reaction solution was filtered, mixed with ethyl acetate, and allowed to stand to obtain a layered mixed solution. The lower layer of the mixed solution is mixed with ethanol, stirred, allowed to stand, filtered, and the resulting filtrate is concentrated under reduced pressure to obtain bear bile powder.

8. The traditional Chinese medicine composition according to claim 1, characterized in that, The borneol mentioned is natural borneol.

9. Use of the traditional Chinese medicine composition according to any one of claims 1 to 8 in the preparation of a drug for treating cataracts.

10. The use according to claim 9, characterized in that, The cataracts referred to are adhesive cataracts, complicated cataracts, traumatic cataracts, or metabolic cataracts.

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