Traditional Chinese medicine composition for treating dry eyes as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating dry eyes as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine compositions. The preparation method of the traditional Chinese medicine composition comprises the following steps: taking 3-12 parts by weight of tripterygium wilfordii and 3-12 parts by weight of mint as raw material medicines, mixing, adding water, decocting, carrying out solid-liquid separation, and concentrating the filtrate to obtain the traditional Chinese medicine composition. According to the invention, tripterygium wilfordii is taken as a main medicine and is matched with mint with the effect of dispelling wind and heat to jointly form the eye fumigating prescription capable of dispelling wind and clearing heat, and the eye fumigating prescription comprises active ingredients such as triptolide, tripterine and the like, and can regulate and control inflammatory response of ocular surface; local administration is carried out by adopting an ultrasonic atomization method, so that liver and kidney injury caused by liver and kidney metabolism of oral medicines can be avoided, most of active ingredients only play roles in eyes and do not enter blood circulation, the toxicity of tripterygium wilfordii is reduced, only anti-inflammatory and immunosuppression efficacy of tripterygium wilfordii is taken, local administration directly reaches a disease site, and the treatment effect on dry eyes is definite.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition for treating dry eyes, and a preparation method and application thereof. Background Art

[0002] Dry eye is a chronic disease associated with multiple factors, which can manifest as symptoms such as eye discomfort and abnormal visual quality, accompanied by pathological changes such as tear film imbalance, ocular surface inflammatory response, and neurological abnormalities. The clinical incidence rate is increasing year by year. Many studies have shown that inflammation plays an important role in the occurrence and development of dry eye. Tear film instability and tear high osmotic pressure will activate the cascade of inflammatory events on the surface of the eyeball, leading to the release of inflammatory mediators into the tears, which in turn leads to damage and apoptosis of lacrimal glands and ocular surface epithelial cells, goblet cell loss, mucin expression disorders, and reduced secretion of aqueous fluid and mucus in tears. Studies have found that anti-inflammatory treatment of the ocular surface has an improvement effect on the three-layer structure of the tear film, and at the same time has a certain protective effect on nerve damage. Therefore, anti-inflammatory treatment is currently an important direction for the treatment of dry eye.

[0003] At present, the main clinical treatments for inflammatory reactions of the ocular surface in dry eyes include glucocorticoids and immunosuppressive eye drops, such as cyclosporine eye drops and fluorometholone eye drops. However, long-term use may lead to risks of glaucoma, cataracts, and toxic lesions of the corneal epithelium. Therefore, finding a class of drugs or prescriptions with "anti-inflammatory and immunosuppressive" effects is the development direction and focus of dry eye treatment.

[0004] As a traditional Chinese herbal medicine, Tripterygium wilfordii has been discovered to have more complex and rich pharmacological effects with the deepening of modern research. Its main active ingredients include triptolide, celastrol, and triptolide. It has strong anti-inflammatory, immunosuppressive, anti-fibrotic, and anti-tumor activities, and can exert effects similar to glucocorticoids and immunosuppressants. However, since Tripterygium wilfordii itself is highly toxic, its clinical application is more restricted. Summary of the invention

[0005] The object of the present invention is to provide a medicine or prescription having "anti-inflammatory and immunosuppressive" effects and being useful for treating dry eyes.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The invention provides a method for preparing a traditional Chinese medicine composition for treating dry eyes, comprising the following steps: taking 3 to 12 parts by weight of tripterygium wilfordii and 3 to 12 parts by weight of mint as raw materials, mixing, decocting with water, separating the solid from the liquid, taking the filtrate, and concentrating to obtain the traditional Chinese medicine composition.

[0008] Preferably, the solid-liquid ratio of the raw material drug to water is 3-12 g: 250-500 mL.

[0009] Preferably, the decocting temperature is 90-100° C. and the decocting time is 10-30 min.

[0010] Preferably, the volume of the decoction obtained after concentration is 1 / 5 to 1 / 2 of the volume before concentration.

[0011] The present invention provides a traditional Chinese medicine composition prepared by the preparation method of the traditional Chinese medicine composition.

[0012] The present invention also provides application of the above-mentioned traditional Chinese medicine composition in preparing medicine for treating dry eyes.

[0013] Preferably, the drug is in the form of an aerosol.

[0014] Preferably, the administration time of the aerosol is 10 to 20 minutes.

[0015] The present invention selects Tripterygium wilfordii as the main drug, and is combined with mint, a traditional Chinese medicine commonly used in clinical practice to dispel wind and heat, to form a prescription for fumigating eyes for dispelling wind and clearing heat. The main active ingredients of the prescription of the present invention include ingredients such as triptolide and triptolide, which have strong anti-inflammatory effects and can regulate the inflammatory response of the ocular surface. At the same time, the present invention adopts an ultrasonic atomization method for local administration, which can avoid liver and kidney damage caused by oral drugs when they are metabolized by the liver and kidneys. In addition, due to the constraints of the blood-ocular barrier and the blood-brain barrier, most of the effective ingredients only play a role locally in the eye and will not enter the blood circulation, so the toxicity of Tripterygium wilfordii can be reduced. The present invention can only take its anti-inflammatory and immunosuppressive effects, and the local administration directly reaches the diseased area, and the therapeutic effect on dry eyes is clear. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a picture of the eye status of the guinea pig before administration in Test Example 2.

[0017] Figure 2 This is a diagram of the eye status of guinea pigs after administration in Test Example 2. DETAILED DESCRIPTION

[0018] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0019] Example 1

[0020] A method for preparing a traditional Chinese medicine composition for treating dry eyes: 6 g of tripterygium wilfordii and 6 g of mint are added with 500 ml of water, boiled at 100° C. for 30 min, and concentrated to 200 ml. The obtained decoction is the traditional Chinese medicine composition.

[0021] Example 2

[0022] A method for preparing a traditional Chinese medicine composition for treating dry eyes: 9 g of tripterygium wilfordii and 9 g of mint are added with 500 ml of water, boiled at 100° C. for 30 min, concentrated to 200 ml, and the obtained water decoction is the traditional Chinese medicine composition.

[0023] Example 3

[0024] A method for preparing a traditional Chinese medicine composition for treating dry eyes: 12 g of tripterygium wilfordii and 12 g of mint are added with 500 ml of water, boiled at 100°C for 30 min, and concentrated to 200 ml. The obtained decoction is the traditional Chinese medicine composition.

[0025] Test Example 1

[0026] Liquid chromatography tandem mass spectrometry (LC-MS / MS) was used to detect 6 samples of decoction and atomized liquid (6 decoction samples were extracted from 6 bags of Chinese medicine decoction, and the preparation method of the 6 bags of Chinese medicine decoction was the same as that in Example 1, and then the prepared 6 bags of Chinese medicine decoction were placed in an ultrasonic atomizer for ultrasonic atomization, and 6 atomized liquids were collected). The decoctions were marked as Y1, Y2, Y3, Y4, Y5, and Y6, and the atomized liquids were marked as M1, M2, M3, M4, M5, and M6, and the average value was taken after each test was performed 3 times. Another bag of Chinese medicine decoction was taken for component testing 3 times, and recorded as liquid 1, liquid 2, and liquid 3. The test results are shown in Table 1:

[0027] Table 1 Changes in pharmacological component content before and after atomization

[0028]

[0029]

[0030] As shown in Table 1, the pharmacological component with the highest concentration is triptolide, with a concentration of 33.925±1.973ng / ml in the water decoction and 30.393±3.303ng / ml in the nebulized liquid, followed by triptolide, with a concentration of 1.582±0.690ng / ml in the water decoction and 0.715±0.315ng / ml in the nebulized liquid, indicating that the water decoction method of triptolide can effectively extract its pharmacological components, and the nebulized liquid still maintains a relatively high drug concentration, which can effectively exert anti-inflammatory pharmacological effects through nebulization.

[0031] Test Example 2

[0032] Security Verification

[0033] The decoction prepared in Example 1 was dripped on the eyes of guinea pigs, twice a day, with a dripping amount of 0.5 mL each time, for 14 days, and the irritation of the drug to the eyes and safety indicators were observed. The main safety detection indicators were: whether the eyes had allergic and irritation reactions, that is, after each treatment, the conjunctiva was checked with a slit lamp for congestion, whether the corneal epithelium was damaged, and whether the eyelids had erythema, rash, etc.

[0034] The eye status of guinea pigs before and after administration Figure 1 , 2 As shown: after the administration, there was no congestion in the conjunctiva of the guinea pig, no damage to the corneal epithelium, and no erythema or rash on the eyelids.

[0035] Test Example 3

[0036] Clinical trials

[0037] A total of 44 subjects were included in the outpatient department of the Ophthalmology Hospital of China Academy of Chinese Medical Sciences from May 2022 to December 2022, of which 4 dropped out and 40 were completed. The experimental group was given the Chinese medicine composition prepared in Example 1 of the present application (6 g of Tripterygium wilfordii, 6 g of mint, 200 mL / dose, and the medicinal materials used were provided and decocted by the Chinese medicine pharmacy of the Ophthalmology Hospital of China Academy of Chinese Medical Sciences). The decocted medicine was placed in an ultrasonic nebulizer (Guangdong Yuehua Medical Instrument Factory Co., Ltd., Guangdong Instrument Registration No.: 20172232004, atomization volume of 2 mL / min, input power of 80 VA; ultrasonic frequency: 1.5 MHZ±10%), and the patient's affected eye was nebulized (the patient opened his eyes during nebulization), 3 times a week, the treatment time was 20 min / time, and the treatment was carried out for 4 weeks, a total of 12 times. The control group was treated with steam fumigation of the placebo (original prescription: 6g of Tripterygium wilfordii, 6g of mint, decocted with water and concentrated to 100mL / dose, diluted with water to prepare a medicine with the same color, taste and quality as Example 1), 3 times a week, 20min / time, for 4 weeks. During the treatment period, both groups were given 0.1% sodium hyaluronate eye drops (Zhenshiming Pharmaceutical Co., Ltd., approval number: National Medicine Standard H20203143) to the affected eyes 3 times / day, and other ocular medications and local treatments were discontinued during the treatment period.

[0038] 1. The comparison results of the effectiveness of the experimental group and the control group in terms of OSDI scores are shown in Table 2: 0-13 points are considered cured; 13-20 points are considered markedly effective; 21-45 points are considered effective, and 46 points or above are considered ineffective.

[0039] Table 2 Comparison of efficacy index between the two groups before and after treatment (%)

[0040]

[0041] As shown in Table 2, the total effective rate of the experimental group was 90%, and the total effective rate of the control group was 60%. The total effective rate of the experimental group was significantly better than that of the control group (χ 2 =17.289, P<0.001)

[0042] 2. The tear film breakup time (BUT value) of the experimental group and the control group before and after treatment was compared. The results are shown in Table 3:

[0043] Table 3 Comparison of tear film breakup time between the two groups before and after treatment [s, M (QL; QU)]

[0044] Group Experimental Group Control group <![CDATA[t # ]]> <![CDATA[P # ]]> Before treatment (n=20) 1(1,2) 2(1,2) -1.286 0.198 After treatment (n=20) 5(3,6) 3(2,4.75) -2.2 0.026 <![CDATA[t * ]]> -3.734b -3.064 / / <![CDATA[P * ]]> ＜0.001 0.002 / /

[0045] As shown in Table 3, both the experimental group and the control group had an improvement effect on the BUT value, and the effect of the experimental group was more obvious.

[0046] 3. The corneal fluorescein staining (FLS) scores of the experimental group and the control group before and after treatment were compared. The results are shown in Table 4:

[0047] Table 4 Comparison of corneal fluorescein staining scores between the two groups before and after treatment (scores, %)

[0048]

[0049] As shown in Table 4, the experimental group had an improvement effect on the FLS value, and the difference was statistically significant (p<0.05), while the control group had no improvement effect on FLS.

[0050] 4. The tear secretion volume of the experimental group and the control group before and after treatment was compared. The results are shown in Table 5:

[0051] Table 5 Comparison of tear secretion between the two groups before and after treatment [mm, M (QL; QU)]

[0052] Group Experimental Group Control group <![CDATA[t # ]]> <![CDATA[P # ]]> Before treatment (n=20) 3(2,5) 4(3,5) -1.126 0.260 After treatment (n=20) 10(8,11) 4(3,6.75) -3.922 ＜0.001 <![CDATA[t * ]]> -3.948 -1.879 / / <![CDATA[P * ]]> ＜0.001 0.060 / /

[0053] As shown in Table 5, the experimental group had an improvement on the SIT value, and the difference was statistically significant, while the control group had no improvement on the SIT.

[0054] In summary, the Chinese medicine composition provided by the present invention can effectively improve the tear film breakup time, corneal fluorescein staining score and tear secretion amount after atomization fumigation administration, and has a clear effect on the treatment of dry eyes.

[0055] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a Chinese medicine composition for treating dry eyes, characterized in that: The method comprises the following steps: taking 3 to 12 parts by weight of tripterygium wilfordii and 3 to 12 parts by weight of mint as raw materials, mixing, boiling with water, separating solid from liquid, taking filtrate, and concentrating to obtain the traditional Chinese medicine composition.

2. The preparation method according to claim 1, characterized in that: The solid-liquid ratio of the raw material drug to water is 3-12 g: 250-500 mL.

3. The preparation method according to claim 2, characterized in that: The decoction temperature is 90-100° C. and the decoction time is 10-30 minutes.

4. The preparation method according to claim 3, characterized in that: The volume of the decoction obtained after concentration is 1 / 5 to 1 / 2 of that before concentration.

5. A Chinese medicine composition prepared by the method for preparing a Chinese medicine composition according to any one of claims 1 to 4.

6. Use of the Chinese medicine composition according to claim 5 in the preparation of a medicament for treating dry eyes.

7. The use according to claim 6, characterized in that The dosage form of the drug is an aerosol.

8. The use according to claim 7, characterized in that The administration time of the atomizer is 10 to 20 minutes.

Images