Traditional Chinese medicine composition for preparing eye lotion, traditional Chinese medicine extract, preparation method and application of traditional Chinese medicine extract, eye lotion and application of eye lotion

Abstract

The invention provides a traditional Chinese medicine composition for preparing eye lotion, a traditional Chinese medicine extract, a preparation method and application of the traditional Chinese medicine composition, the traditional Chinese medicine extract, the eye lotion and application of the eye lotion. The traditional Chinese medicine composition is prepared from fructus lycii, rhizoma polygonati, flos chrysanthemi indici and herba menthae, and the traditional Chinese medicine extract comprises the extract of the traditional Chinese medicine composition. The eye moistening liquid comprises the traditional Chinese medicine extract. According to the traditional Chinese medicine composition, the fructus lycii serves as a monarch drug, the rhizoma polygonati serves as a ministerial drug, the flos chrysanthemi indici serves as an adjuvant drug, the herba menthae serves as a conductant drug, the principle of tonifying the liver to improve eyesight is followed in treatment, the extract of the traditional Chinese medicine composition contains a large amount of polysaccharide, linarin and menthol active ingredients, the extract of the traditional Chinese medicine composition is applied to preparation of the eye moistening liquid, and the eye moistening effect is good. The obtained eye lotion is free of toxic and side effects and has the effects of promoting tear secretion and repairing corneal injury.

Description

Technical Field

[0001] The present invention belongs to the technical field of Chinese medicine compositions and Chinese medicine preparations, and specifically relates to a Chinese medicine composition for preparing eye drops, a Chinese medicine extract and a preparation method and application thereof, and an eye drops and an application thereof. Background Art

[0002] The ocular surface is an important gateway to the eye. It is exposed to the outside and can be affected by various external factors, making it prone to inflammation and infection. Damage to the ocular surface can occur for a variety of reasons. The characteristics of ocular surface damage are corneal staining, corneal epithelial detachment, and even corneal ulcers. In most cases, the tears secreted by the lacrimal glands contain substances that can repair the ocular surface, which can repair minor damage to the ocular surface; however, if the state of the ocular surface changes, such as dry eyes, it can cause damage to the ocular surface that is difficult to repair. This requires the use of drugs that can repair ocular surface damage for treatment. Existing drugs for repairing ocular surface damage generally have complex ingredients, cumbersome preparation methods, high long-term toxicity, or poor efficacy. Summary of the invention

[0003] One of the purposes of the present invention is to provide a Chinese medicine composition for preparing eye drops and its application. The Chinese medicine composition of the present invention uses wolfberry as a main medicine, polygonatum as a ministerial medicine, wild chrysanthemum as an adjuvant medicine, and mint as a guiding medicine. The raw materials are simple and follow the principle of "tonifying the liver and improving eyesight" in treatment. The Chinese medicine composition is used to prepare eye drops. The obtained eye drops have no toxic side effects and have the effects of promoting tear secretion and repairing corneal damage. The eye drops can be used in the preparation of medicaments for treating dry eyes.

[0004] The second purpose of the present invention is to provide a Chinese herbal medicine extract for preparing eye drops, and its preparation method and application. The Chinese herbal medicine extract contains a large amount of polysaccharides, menthol and menthol active ingredients. It is used to prepare eye drops. The obtained eye drops have no toxic side effects and have the effects of promoting tear secretion and repairing corneal damage. It can be used to prepare medicines for treating dry eyes.

[0005] The third purpose of the present invention is to provide an eye-lubricating liquid and its preparation method and application. The eye-lubricating liquid has no toxic side effects and has the effects of promoting tear secretion and repairing corneal damage. It has good application prospects when used in the preparation of a medicament for treating dry eye.

[0006] The above objects of the present invention are achieved through the following technical solutions:

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition for preparing eye drops, wherein the traditional Chinese medicine composition consists of wolfberry, polygonatum, wild chrysanthemum and mint.

[0008] In some embodiments of the present invention, the weight portion of wolfberry in the traditional Chinese medicine composition is 10-15 parts, the weight portion of polygonatum is 10-15 parts, the weight portion of wild chrysanthemum is 8-12 parts, and the weight portion of mint in terms of menthol is 0.01-0.2 parts.

[0009] In a second aspect, the present invention provides use of the Chinese medicine composition described in the first aspect in the preparation of eye drops or medicaments for treating dry eyes.

[0010] In a third aspect, the present invention provides a Chinese herbal extract for preparing eye drops, wherein the Chinese herbal extract comprises an extract of the Chinese herbal composition described in the first aspect, preferably comprising an aqueous extract of wolfberry, an aqueous extract of polygonatum, an aqueous extract of wild chrysanthemum, and menthol.

[0011] In a fourth aspect, the present invention provides a method for preparing the Chinese medicine extract described in the third aspect, the method comprising refluxing 10 to 15 parts by weight of wolfberry and 10 to 15 parts by weight of polygonatum with 75 to 90% by volume ethanol, recovering the residues, then decocting the recovered residues and 8 to 12 parts by weight of wild chrysanthemum with water to recover the medicinal liquid; finally, mixing the recovered medicinal liquid with 0.01 to 0.2 parts by weight of menthol to obtain the Chinese medicine extract.

[0012] In some embodiments of the present invention, the solid-liquid ratio of the reflux is 1:(5-15), preferably 1:(8-12); and / or the number of reflux is 1-3 times; and / or the reflux time is 30-90 min each time, preferably 45-75 min, and more preferably 60 min.

[0013] In some embodiments of the present invention, the solid-liquid ratio of the decoction is 1:(8-16), preferably 1:(10-15); and / or the number of decoctions is 2-5 times, and recovering the medicinal liquid means recovering the medicinal liquid of each decoction and combining them; and / or the decoction time is 30-90 min each time, preferably 45-75 min, and more preferably 60 min.

[0014] In some embodiments of the present invention, wolfberry and polygonatum can be refluxed separately or together.

[0015] In some embodiments of the present invention, the wolfberry residue, polygonatum residue and wild chrysanthemum can be decocted separately or mixed and decocted.

[0016] In some embodiments of the present invention, the volume fraction of ethanol for refluxing is 80-90%, preferably 80-85%, and more preferably 80%.

[0017] In some embodiments of the present invention, the method further comprises crushing wolfberry and polygonatum before refluxing to obtain wolfberry coarse powder and polygonatum coarse powder.

[0018] In some embodiments of the present invention, the method further comprises crushing the wild chrysanthemum before decocting to obtain wild chrysanthemum coarse powder.

[0019] In some embodiments of the present invention, the method further comprises filtering the recovered drug solution, preferably, using a 30-45 mesh sieve for filtering.

[0020] In some embodiments of the present invention, the method further comprises soaking the material to be decocted for 20 to 30 hours before decocting.

[0021] In some embodiments of the present invention, the specific processes of the preparation method of the traditional Chinese medicine extract can be divided into three types, wherein process one comprises the following steps:

[0022] a. Take 10 to 15 parts by weight of wolfberry, 10 to 15 parts by weight of Polygonatum, mix well, and then reflux with a volume fraction of 75 to 90% ethanol, discard the reflux solution to retain the residue;

[0023] b Take 8 to 12 parts by weight of wild chrysanthemum, wild chrysanthemum, water and the residue obtained in step a mixed, and then boiled, recovering the liquid;

[0024] c. The liquid recovered in step b is mixed with 0.01 to 0.2 parts by weight of menthol to obtain a Chinese herbal extract.

[0025] In some embodiments of the present invention, in step a, the solid-liquid ratio of the reflux is 1:(5-15), preferably 1:(8-12); and / or the number of refluxes is 1 to 3 times; and / or the reflux time is 30 to 90 minutes each time, preferably 45 to 75 minutes, and more preferably 60 minutes.

[0026] In some embodiments of the present invention, step a further includes crushing wolfberry and polygonatum separately before taking wolfberry and polygonatum, and then taking wolfberry coarse powder and polygonatum coarse powder and mixing them evenly; or, crushing the mixture of wolfberry and polygonatum before refluxing to obtain coarse powder of wolfberry and polygonatum.

[0027] In some embodiments of the present invention, in step b, the solid-liquid ratio of the decoction is 1:(8-16), preferably 1:(10-15); and / or the number of decoctions is 2-5 times, and recovering the medicinal liquid means recovering the medicinal liquid of each decoction and combining them; and / or the decoction time is 30-90 min each time, preferably 45-75 min, and more preferably 60 min.

[0028] In some embodiments of the present invention, the step b further comprises crushing the wild chrysanthemum before mixing the wild chrysanthemum, water and the medicinal residue obtained in step a to obtain wild chrysanthemum coarse powder.

[0029] In some embodiments of the present invention, the step b further comprises filtering the recovered drug solution, preferably using a 30-45 mesh sieve for filtering.

[0030] In some embodiments of the present invention, step b further includes soaking for 20 to 30 hours after mixing and then decocting; that is, step b is: taking 8 to 12 parts by weight of wild chrysanthemum, mixing the wild chrysanthemum, water and the medicinal residue obtained in step (a), soaking them for 20 to 30 hours, then decocting, and recovering the medicinal liquid.

[0031] Process 2 includes the following steps:

[0032] (a) taking 10 to 15 parts by weight of wolfberry, refluxing the wolfberry with 75 to 90% by volume ethanol, discarding the reflux solution and retaining the wolfberry residue;

[0033] (b) taking 10 to 15 parts by weight of polygonatum sibiricum, refluxing the polygonatum sibiricum with 75 to 90% by volume ethanol, discarding the reflux liquid and retaining the polygonatum sibiricum residue;

[0034] (c) taking 8 to 12 parts by weight of wild chrysanthemum, mixing the wild chrysanthemum, water, the wolfberry residue obtained in step (a), and the polygonatum residue obtained in step (b), then decocting and recovering the liquid medicine;

[0035] (d) mixing the medicinal solution recovered in step (c) with 0.01 to 0.2 parts by weight of menthol to obtain a Chinese herbal medicine extract.

[0036] In some embodiments of the present invention, in steps (a) and (b), the solid-liquid ratio of the reflux is 1:(5-15), preferably 1:(8-12); and / or the number of refluxes is 1 to 3 times; and / or the reflux time is 30 to 90 minutes each time, preferably 45 to 75 minutes, and more preferably 60 minutes.

[0037] In some embodiments of the present invention, the step (a) further comprises crushing the wolfberries before refluxing to obtain coarse wolfberry powder.

[0038] In some embodiments of the present invention, the step (b) further comprises crushing the polygonatum before refluxing to obtain coarse polygonatum powder.

[0039] In some embodiments of the present invention, in step (c), the solid-liquid ratio of the decoction is 1:(8-16), preferably 1:(10-15); and / or the number of decoctions is 2-5 times, and recovering the medicinal liquid means recovering the medicinal liquid of each decoction and combining them; and / or the decoction time is 30-90 min each time, preferably 45-75 min, and more preferably 60 min.

[0040] In some embodiments of the present invention, the step (c) further comprises crushing the wild chrysanthemum before mixing to obtain wild chrysanthemum coarse powder.

[0041] In some embodiments of the present invention, the step (c) further comprises filtering the recovered drug solution, preferably using a 30-45 mesh sieve for filtering.

[0042] In some embodiments of the present invention, step (c) further includes soaking for 20 to 30 hours after mixing and then decocting; that is, step (c) is: taking 8 to 12 parts by weight of wild chrysanthemum, mixing the wild chrysanthemum, water, the wolfberry residue obtained in step (a), and the polygonatum residue obtained in step (b), and then soaking them for 20 to 30 hours, then decocting, and recovering the medicinal liquid.

[0043] Process three includes the following steps:

[0044] a) taking 10 to 15 parts by weight of wolfberry, refluxing the wolfberry with 75 to 90% by volume ethanol, then discarding the reflux solution and retaining the medicinal residue to obtain the wolfberry medicinal residue; then adding water to the wolfberry medicinal residue for decoction, recovering the medicinal solution, and obtaining an aqueous extract of wolfberry;

[0045] b) taking 10 to 15 parts by weight of polygonatum, refluxing the polygonatum with 75 to 90% by volume ethanol, discarding the reflux solution and retaining the residue to obtain polygonatum residue; then adding water to the polygonatum residue for decoction, recovering the liquid, and obtaining a water extract of polygonatum;

[0046] c) taking 8 to 12 parts by weight of wild chrysanthemum, adding water to boil, recovering the medicinal liquid, and obtaining an aqueous extract of wild chrysanthemum;

[0047] d) mixing the water extract of wolfberry obtained in step a), the water extract of polygonatum obtained in step b), and the water extract of wild chrysanthemum obtained in step c) with 0.01-0.2 parts by weight of menthol to obtain a traditional Chinese medicine extract.

[0048] In some embodiments of the present invention, in steps a) and b), the solid-liquid ratio of the reflux is 1:(5-15), preferably 1:(8-12); and / or the number of refluxes is 1 to 3 times; and / or the reflux time is 30 to 90 minutes each time, preferably 45 to 75 minutes, and more preferably 60 minutes.

[0049] In some embodiments of the present invention, the step a) further comprises crushing the wolfberries before refluxing to obtain coarse wolfberry powder.

[0050] In some embodiments of the present invention, the step b) further comprises crushing the polygonatum before refluxing to obtain coarse polygonatum powder.

[0051] In some embodiments of the present invention, in steps a), b) and c), the solid-liquid ratio of the decoction is 1:(8-16), preferably 1:(10-15); and / or the number of decoctions is 2-5 times, and recovering the medicinal liquid means recovering the medicinal liquid of each decoction and combining them; and / or the decoction time is 30-90 min each time, preferably 45-75 min, and more preferably 60 min.

[0052] In some embodiments of the present invention, the steps a), b) and c) further include soaking for 20 to 30 hours before decocting after adding water.

[0053] In some embodiments of the present invention, the step c) further comprises crushing the wild chrysanthemum before decocting to obtain wild chrysanthemum coarse powder.

[0054] In some embodiments of the present invention, the step d) further comprises filtering the mixed medicinal solution, preferably, using a 30-45 mesh sieve for filtering.

[0055] In a fifth aspect, the present invention provides the use of the Chinese herbal extract described in the third aspect and / or the Chinese herbal extract prepared by the preparation method of the Chinese herbal extract described in the fourth aspect in the preparation of eye drops or medicaments for treating dry eyes.

[0056] In a sixth aspect, the present invention provides an eye-lubricating solution, comprising the Chinese herbal extract described in the third aspect or the Chinese herbal extract prepared by the preparation method described in the fourth aspect.

[0057] In some embodiments of the present invention, the eye drops contain no less than 1.4 mg / mL of total polysaccharides, no less than 0.067 mg / mL of montmorillonine, and a menthol concentration of 0.01 to 0.2 g / mL.

[0058] In some embodiments of the present invention, the total polysaccharide concentration in the eye drops is 1.4-8.3 mg / mL, the lignocerin concentration is 0.067-0.4 mg / mL, and the menthol concentration is 0.01-0.2 g / mL.

[0059] In some embodiments of the present invention, the pH value of the eye drops is 7-7.8, and the osmotic pressure is 280-290 mOsm / L.

[0060] Normal tears have a pH value of 7.35 and an osmotic pressure of 295-309 mOsm / L; the pH value of tears of patients with dry eyes is lower than 7.35 and the osmotic pressure is higher than 309 mOsm / L. The use of the eye drops of the present invention can increase the pH value of tears of patients with dry eyes and reduce the osmotic pressure of tears of patients with dry eyes.

[0061] In some embodiments of the present invention, the eye drops further include excipients. Preferably, the excipients include any one or more of a surfactant, a pH regulator, an osmotic pressure regulator, and a buffer solution.

[0062] In some embodiments of the present invention, the surfactant is Tween-80; preferably, the concentration of the Tween-80 in the eye drops is 0.08-2 g / mL, preferably 0.25-1 g / mL; more preferably, in the eye drops, the ratio of the concentration of the Tween-80 to the concentration of the menthol is greater than or equal to 5, preferably 5-10, more preferably 5-8.

[0063] In some embodiments of the present invention, the amount of the pH adjuster is the amount used to adjust the pH value of the eye drops to 7.0-7.5; preferably, the pH adjuster is sodium hydroxide or potassium hydroxide; more preferably, the concentration of sodium hydroxide or potassium hydroxide in the pH adjuster is 0.1 mol / L.

[0064] In some embodiments of the present invention, the concentration of the osmotic pressure regulator in the eye solution is an amount used to adjust the osmotic pressure of the eye solution to 280-290 mOsm / L; preferably, the osmotic pressure regulator is sodium chloride or potassium chloride; more preferably, the concentration of the osmotic pressure regulator in the eye solution is 8.0-9.0 g / mL.

[0065] In some embodiments of the present invention, the buffer solution is a phosphate buffer solution; preferably, the concentration of the phosphate buffer solution in the eye drops is an amount that can stabilize the pH value of the eye drops between 7.0 and 7.5.

[0066] In the seventh aspect, the present invention provides a method for preparing the eye drops described in the sixth aspect, the preparation method comprising the following steps: adjusting the pH value of the Chinese medicine extract to 7-7.8 and the osmotic pressure to 280-290 mOsm / L; then adding water to adjust the concentration of the active ingredients in the Chinese medicine extract to the range for clinical use; and then sterilizing, filtering, filling and packaging the liquid medicine to obtain the finished product.

[0067] In some embodiments of the present invention, the preparation method comprises the following steps:

[0068] Ⅰ. Add Tween-80 to the Chinese herbal medicine extract and mix well;

[0069] Ⅱ. Use 0.1 mol / L sodium hydroxide or potassium hydroxide solution and phosphate buffer to adjust the pH value of the mixed solution obtained in step Ⅰ to 7.0-7.5; then add sodium chloride or potassium chloride to adjust the osmotic pressure to 280-290 mOsm / L; then add water to adjust the concentration of the active ingredient in the drug solution to the intended clinical range;

[0070] III. The liquid medicine obtained in step II is sterilized, filtered, filled and packaged to obtain the finished product.

[0071] In some embodiments of the present invention, the Tween-80 can be mixed with menthol and added to the medicinal solution containing the water extract of wolfberry, the water extract of polygonatum, and the water extract of wild chrysanthemum to enhance the solubility of menthol in the medicinal solution.

[0072] In some embodiments of the present invention, the preparation method comprises the following steps:

[0073] (I) 10 to 15 parts by weight of wolfberry and 10 to 15 parts by weight of polygonatum are refluxed with 75 to 90% by volume ethanol to recover the residues, and then the recovered residues and 8 to 12 parts by weight of wild chrysanthemum are boiled in water to recover the liquid medicine.

[0074] (II) Take 0.01-0.2 parts by weight of menthol and 5 times the weight of Tween-80 of the menthol, add appropriate amount of water to grind and dissolve, add to the liquid medicine recovered in step (I), and mix well.

[0075] (III) The pH value of the mixed solution obtained in step (II) is adjusted to 7.0-7.5 with 0.1 mol / L sodium hydroxide or potassium hydroxide solution and phosphate buffer; then sodium chloride or potassium chloride is added to adjust the osmotic pressure to 280-290 mOsm / L; and water is then added to adjust the concentration of the active ingredient in the solution to the intended clinical range.

[0076] (IV) sterilizing, filtering, filling and packaging the liquid medicine obtained in step III to obtain a finished product.

[0077] In some embodiments of the present invention, the solid-liquid ratio of the reflux in step (I) is 1: (5-15), preferably 1: (8-12); and / or the number of reflux is 1 to 3 times; and / or the reflux time is 30 to 90 minutes each time, preferably 45 to 75 minutes, and more preferably 60 minutes.

[0078] In some embodiments of the present invention, the solid-liquid ratio of the decoction in step (I) is 1:(8-16), preferably 1:(10-15); and / or the number of decoctions is 2-5 times, and recovering the medicinal liquid means recovering the medicinal liquid of each decoction and combining them; and / or the decoction time is 30-90 min each time, preferably 45-75 min, and more preferably 60 min.

[0079] In some embodiments of the present invention, the volume fraction of ethanol used for reflux in step (I) is 80-90%, preferably 80-85%, and more preferably 80%.

[0080] In some embodiments of the present invention, in step (I), wolfberry and polygonatum can be refluxed separately or together.

[0081] In some embodiments of the present invention, in step (I), the wolfberry residue, polygonatum residue and wild chrysanthemum can be decocted separately or mixed and decocted.

[0082] In some embodiments of the present invention, step (I) further comprises crushing wolfberry and polygonatum before refluxing to obtain wolfberry coarse powder and polygonatum coarse powder.

[0083] In some embodiments of the present invention, step (I) further comprises crushing the wild chrysanthemum before decocting to obtain wild chrysanthemum coarse powder.

[0084] In some embodiments of the present invention, step (I) further comprises filtering the recovered drug solution, preferably using a 30-45 mesh sieve for filtering.

[0085] In some embodiments of the present invention, step (I) further comprises soaking the material to be decocted for 20 to 30 hours before decocting.

[0086] In some embodiments of the present invention, the intended clinical use range refers to a total polysaccharide concentration of 1.4 to 8.3 mg / mL, a montmorillonine concentration of 0.067 to 0.4 mg / mL, and a menthol concentration of 0.01 to 0.2 g / mL.

[0087] In an eighth aspect, the present invention provides use of the eye lubricating solution described in the sixth aspect or the eye lubricating solution prepared by the preparation method of the eye lubricating solution described in the seventh aspect in the preparation of a medicament for treating dry eye.

[0088] The compatibility principles of the Chinese medicine composition of the present invention and the main effects of the Chinese medicinal materials are introduced as follows:

[0089] The Chinese medicine composition of the present invention uses wolfberry as the main medicine, polygonatum as the ministerial medicine, wild chrysanthemum as the adjuvant, and mint as the guiding medicine, and follows the principle of "tonifying the liver and improving eyesight" in treatment. As the main medicine, wolfberry plays a main role in the Chinese medicine composition; wolfberry has both the effect of nourishing the liver and kidney and the antioxidant effect, and can effectively improve vision and relieve eye fatigue. As the ministerial medicine, polygonatum is mainly used to enhance the efficacy of the main medicine in the Chinese medicine composition; polygonatum has the effects of nourishing the spleen and replenishing qi, moistening the lungs and promoting fluid production, which can not only strengthen the nourishment of wolfberry to the liver and kidney, but also regulate the body function and improve the overall health level. As an adjuvant, wild chrysanthemum can not only solve the problems of eye inflammation accompanied by dry eyes, but also can reconcile the efficacy of wolfberry and polygonatum. As the guiding medicine, the active ingredient menthol of mint has a cooling property, which can guide other drugs to quickly reach the affected area and provide immediate relief. The inventor's previous research shows that an appropriate amount of menthol can promote blood circulation and further improve the absorption efficiency of other ingredients in the eye drops. In the eye drops of the present invention, each component not only plays a role independently, but also synergizes with other components to achieve the best therapeutic effect.

[0090] Lycium barbarum is the dried mature fruit of Lycium barbarrumL., a plant of the Solanaceae family. Lycium barbarum is mainly used to treat liver and kidney yin deficiency, blurred vision, dry and painful eyes. It belongs to the liver, kidney and lung meridians and can nourish the kidneys, liver and improve eyesight. Lycium barbarum contains Lycium barbarum polysaccharides, carotene, betaine, vitamin C, vitamin B1, vitamin B2, niacin, scopolamine, scopolamine, aspartic acid, glutamic acid, etc.; there are also a large number of mineral elements, such as potassium, sodium, calcium, magnesium, copper, manganese, zinc, selenium, etc.; it has the effects of immunomodulation, anti-aging, anti-injury, and hypoglycemic.

[0091] Polygonatum sibiricum Red is the dried rhizome of Polygonatum sibiricum Red, a plant of the Liliaceae family. Polygonatum sibiricum Red is mild in nature and sweet in taste. It enters the spleen, lung, and kidney meridians, nourishes yin and moistens the lungs, replenishes the spleen and replenishes qi, and nourishes the kidneys and replenishes essence. Polygonatum sibiricum Red contains Polygonatum sibiricum polysaccharides, saponins, flavonoids, anthraquinones, etc., and has anti-inflammatory, antiviral, hypoglycemic, and anti-tumor effects.

[0092] Wild chrysanthemum is the dried inflorescence of Chrysanthemumindicum L., a plant of the Asteraceae family. Wild chrysanthemum is slightly cold, pungent and bitter, and enters the liver and heart meridians, clearing away heat and detoxifying. Wild chrysanthemum contains terpenes, flavonoids, parthenol, chlorogenic acid, monanthin, etc., and has anti-inflammatory, antibacterial, and antiviral effects.

[0093] Mint is the dried whole herb of Mentha haplocalyx Briq., a plant of the Lamiaceae family. Mint is pungent and cool in nature, and has the effects of dispelling wind, clearing heat, and detoxifying. Menthol extracted from the leaves and stems of mint is used as a stimulant in medicine, acting on the skin or mucous membranes, with a cooling and itchy effect; it can be taken internally as a wind-repellent, for headaches and inflammation of the nose, pharynx, and throat.

[0094] The beneficial effects of the present invention are as follows:

[0095] The Chinese medicine composition of the present invention uses wolfberry as the main medicine, polygonatum as the auxiliary medicine, wild chrysanthemum as the adjuvant medicine, and mint as the guiding medicine. It follows the principle of "tonifying the liver and improving eyesight" in treatment. The four medicinal materials are compatible with each other to promote tear secretion and repair corneal damage.

[0096] The Chinese medicine extract of the present invention contains a large amount of Lycium barbarum polysaccharide, Polygonatum sibiricum polysaccharide, mongoside and menthol active ingredients. The Chinese medicine extract is used to prepare eye drops. The obtained eye drops have no toxic side effects and have the effects of promoting tear secretion and repairing corneal damage, and can be used to prepare medicaments for treating dry eyes. The Chinese medicine extract preparation method of the present invention is simple to operate and is conducive to industrial production; and in the preparation method of the present invention, firstly, Lycium barbarum and Polygonatum sibiricum are refluxed with ethanol with a volume fraction of 75-90% to remove the alcohol-soluble components therein, and then the dregs obtained after reflux are boiled with water, and the obtained water extract has high polysaccharide content and good drug efficacy; wild chrysanthemum is boiled to effectively extract the mongoside active ingredient to obtain a water extract with a high mongoside content; menthol is directly used as medicine, the raw materials are easier to obtain and the menthol content in the Chinese medicine extract can be effectively guaranteed to be stable and the toxicity and cost of the Chinese medicine extract can be reduced.

[0097] The eye drops of the present invention have simple ingredients, no toxic side effects, and have the effects of promoting tear secretion and repairing corneal damage. The eye drops of the present invention have good application prospects in the preparation of medicaments for treating dry eyes. BRIEF DESCRIPTION OF THE DRAWINGS

[0098] Figure 1 The present invention is a flow chart of the preparation process of the eye drops according to Example 1.

[0099] Figure 2 This is the standard curve for determining the total polysaccharide content in eye drops.

[0100] Figure 3 This is the standard curve for determining the content of magnoflorin in eye drops.

[0101] Figure 4 This is the HPLC chromatogram of the product when the eye drops are prepared without wild chrysanthemum. DETAILED DESCRIPTION

[0102] The following examples further illustrate the technology of the present invention. These examples are for illustration and example of the present invention and are not intended to limit the scope of the present invention in any form.

[0103] Example 1

[0104] An eye-lubricating liquid is prepared by a preparation method comprising the following steps. The process flow chart of the preparation method is as follows: Figure 1 As shown, the specific steps are as follows:

[0105] (1) Take 12.5 g of wolfberry and 12.5 g of polygonatum, grind the wolfberry and polygonatum to obtain coarse powder of wolfberry and polygonatum, add 10 times the volume fraction of 80% ethanol to reflux the coarse powder twice, each time for 1 hour, and discard the reflux liquid to retain the residue.

[0106] (2) Take 10g of wild chrysanthemum and mix it with the residue obtained in step (1), add 12 times the amount of distilled water and soak for 24h, then decoct for 3 times, each time for 1h, recover the decoction obtained from each decoction and combine them, and filter the obtained combined decoction with a 40 mesh to recover the filtrate.

[0107] (3) Take 0.1 g of menthol and 0.5 g of Tween-80, add an appropriate amount of distilled water, grind and dissolve, then add to the filtrate recovered in step (2), and mix well.

[0108] (4) The pH value of the mixed solution obtained in step (3) was adjusted to 7.0-7.5 using 0.1 mol / L NaOH solution and phosphate buffer solution; then 8.5 g NaCl was added to adjust the osmotic pressure to 280-290 mOsm / L; and distilled water was added to 1000 mL.

[0109] (5) sterilizing the liquid medicine obtained in step (4) at 121° C. for 30 min, and then filtering it through a 0.45 μm microporous filter membrane; filling the liquid medicine into a bottle at a specification of 2 mL / bottle, and then labeling and packaging the filled eye drops to obtain a finished product.

[0110] The product usage and dosage are as follows: apply to the eyelids; 1 to 2 drops at a time, 3 to 5 times a day; increase the dosage if necessary.

[0111] The product should be stored in sealed container in a cool and dry place.

[0112] The validity period of the product is set to 24 months.

[0113] Example 2

[0114] An eye-lubricating liquid is prepared by a preparation method comprising the following steps:

[0115] (1) Take 6.25 g of wolfberry and 6.25 g of polygonatum, grind the wolfberry and polygonatum to obtain coarse powder of wolfberry and polygonatum, add 10 times the volume fraction of 80% ethanol to reflux the coarse powder twice, each time for 1 hour, and discard the reflux liquid to keep the residue.

[0116] (2) Take 5 g of wild chrysanthemum and mix it with the residue obtained in step (1), add 12 times the amount of distilled water and soak for 24 hours, then decoct for 3 times, each time for 1 hour, recover the decoction obtained from each decoction and combine them, and filter the obtained combined decoction with a 40 mesh to recover the filtrate.

[0117] (3) Take 0.05 g of menthol and 0.25 g of Tween-80, add an appropriate amount of distilled water, grind and dissolve, then add to the filtrate recovered in step (2), and mix well.

[0118] (4) The pH value of the mixed solution obtained in step (3) was adjusted to 7.0-7.5 using 0.1 mol / L NaOH solution and phosphate buffer solution; then 8.5 g NaCl was added to adjust the osmotic pressure to 280-290 mOsm / L; and distilled water was added to 1000 mL.

[0119] (5) sterilizing the liquid medicine obtained in step (4) at 121° C. for 30 min, and then filtering it through a 0.45 μm microporous filter membrane; filling the liquid medicine into a bottle at a specification of 2 mL / bottle, and then labeling and packaging the filled eye drops to obtain a finished product.

[0120] Example 3

[0121] An eye-lubricating liquid is prepared by a preparation method comprising the following steps:

[0122] (1) Take 25 g of wolfberry and 25 g of polygonatum, grind the wolfberry and polygonatum to obtain coarse powder of wolfberry and polygonatum, add 10 times the volume fraction of 80% ethanol to reflux the coarse powder twice, each time for 1 hour, and discard the reflux liquid to keep the residue.

[0123] (2) Take 20g of wild chrysanthemum and mix it with the residue obtained in step (1), add 12 times the amount of distilled water and soak for 24h, then decoct for 3 times, each time for 1h, recover the decoction obtained from each decoction and combine them, and filter the obtained combined decoction with a 40 mesh to recover the filtrate.

[0124] (3) Take 0.2 g of menthol and 1 g of Tween-80, add an appropriate amount of distilled water, grind and dissolve, then add to the filtrate recovered in step (2), and mix well.

[0125] (4) The pH value of the mixed solution obtained in step (3) was adjusted to 7.0-7.5 using 0.1 mol / L NaOH solution and phosphate buffer solution; then 8.5 g NaCl was added to adjust the osmotic pressure to 280-290 mOsm / L; and distilled water was added to 1000 mL.

[0126] (5) sterilizing the liquid medicine obtained in step (4) at 121° C. for 30 min, and then filtering it through a 0.45 μm microporous filter membrane; filling the liquid medicine into a bottle at a specification of 2 mL / bottle, and then labeling and packaging the filled eye drops to obtain a finished product.

[0127] The total polysaccharide content in the finished product prepared in Example 1 was determined by phenol-sulfuric acid method and high performance liquid chromatography The content of linaloside in the finished product prepared in Example 1 was determined by spectroscopy.

[0128] (I) Determination of total polysaccharide content

[0129] Preparation of glucose reference solution: Accurately weigh 25 mg of anhydrous glucose reference substance dried to constant weight, place it in a 250 mL volumetric flask, add water to dissolve, and dilute to the scale to make a glucose reference solution.

[0130] Preparation of phenol reagent: Take an appropriate amount of phenol, add 0.5g aluminum sheet, distill and collect the fraction at 180-182℃, weigh 12.5g of the fraction and place it in a 250mL brown volumetric flask, dilute with water to the scale, shake well, protect from light, and refrigerate.

[0131] Drawing of standard curve: accurately pipette 0.2mL, 0.4mL, 0.6mL, 0.8mL, and 1.0mL of glucose reference solution into 10mL stoppered test tubes, accurately add 1.8mL, 1.6mL, 1.4mL, 1.2mL, and 1.0mL of distilled water to make the total volume of the solution in each test tube 2mL, add 1.0mL of the phenol reagent prepared above to each test tube, mix well, then accurately add 5mL of concentrated H2SO4 to each test tube, shake and place for 10min, heat in a boiling water bath for 15min, then cool in cold water, use distilled water as blank control, measure absorbance at a wavelength of 490nm, use the concentration of glucose reference (mg / mL) as the horizontal coordinate and the absorbance (A) as the vertical coordinate, and draw the standard curve as shown in the figure. Figure 2 As shown, the standard curve equation is:

[0132] y=0.1325x-0.0081, r=0.9994 (n=5).

[0133] Preparation of the test solution: Accurately measure 10 mL of the finished product prepared in Example 1, add anhydrous ethanol to make the alcohol content 80%. Collect the polysaccharide precipitate, wash it with acetone several times, and dissolve the precipitate with 10 mL of distilled water. Extract and shake the crude polysaccharide solution with 5 mL of a mixture of n-butanol and chloroform (volume ratio of 1:1) for 3 times, separate the lower protein layer, and collect the supernatant. Add 0.5% activated carbon to the supernatant, boil for 30 minutes, filter, dilute to 100 mL, take 10 mL and place it in a 50 mL brown volumetric flask, dilute to the scale, and set aside.

[0134] Determination of total polysaccharide content: Accurately aspirate 1 mL of the test solution, accurately add 1.0 mL of distilled water, then add 1.0 mL of the phenol reagent prepared above, mix well, then accurately add 5 mL of concentrated H2SO4, shake and let stand for 10 minutes, heat in a boiling water bath for 15 minutes, then cool in cold water, use distilled water as a blank control, measure the absorbance at a wavelength of 490 nm, and calculate the total polysaccharide content based on the standard curve equation obtained above to be 2.7685 mg / mL.

[0135] (II) Determination of the content of montmorillonine

[0136] HPLC conditions:

[0137] The chromatographic column was CAPCELL PAK C18 UG120 (250 mm*4.6 mm, 5 μm), and the column temperature was room temperature;

[0138] The mobile phase was methanol-0.08% phosphoric acid in water (56:44) with a flow rate of 1.0 mL / min;

[0139] The detection wavelength is 326nm and the theoretical plate number is not less than 1000.

[0140] Reagents: Phosphoric acid (analytical grade) and methanol (analytical grade) were sourced from Beijing Chemical Plant; the reagents used for HPLC were all chromatographic grade, and the water was ultrapure water.

[0141] Menghua glycoside reference substance: 111528-200605, provided by China Food and Biological Products Control Institute.

[0142] Preparation of limonene glycoside reference solution: Accurately weigh 3.09 mg of limonene glycoside dried to constant weight over phosphorus pentoxide, place it in a 25 mL volumetric flask, add methanol to dissolve it, and then dilute to the scale to prepare the limonene glycoside reference solution.

[0143] Drawing of standard curve: Take 1μL, 2μL, 3μL, 5μL, and 6μL of the linalool reference solution and inject them respectively. With the reference sample injection volume x (μg) as the horizontal axis and the peak area integral value y as the vertical axis, draw the standard curve as shown in the figure below: Figure 3 As shown, the standard curve equation is: y = 785.44x-20.038, r = 0.9996. The results show that the linalool has a good linear relationship with the peak area in the range of 0.1236 to 0.7416 μg injection amount.

[0144] Preparation of the test solution: Take 100 mL of the finished product prepared in Example 1, evaporate to dryness in a water bath, add 50 mL of methanol to the residue and ultrasonically extract for 30 min, filter, place the filtrate in a 100 mL volumetric flask, and dilute to the mark to obtain the test solution.

[0145] Determination of the content of lignoside: Accurately aspirate 5 μL of the test solution, inject it into the liquid chromatograph, and determine; the content of lignoside obtained is 0.1334 mg / mL.

[0146] Toxicology study of the eye drops prepared by the present invention

[0147] The sources of animals and some drugs used in this experiment are as follows:

[0148] Mice, rabbits, and guinea pigs were obtained from the Department of Laboratory Animal Science, Peking University Health Science Center;

[0149] Physiological saline was obtained from Sichuan Shule Pharmaceutical Co., Ltd.

[0150] (I) Acute toxicity test

[0151] On the first day, 50 mL / kg of the finished eye solution prepared in Example 1 was injected intraperitoneally into mice, and then the mice were fed normally. No mice died after continuous observation for 14 days. The maximum tolerance of the mice to the eye solution was 50 mL / kg, which was equivalent to 8333 times the clinical daily dose, indicating that the eye solution of the present invention had no obvious acute toxicity.

[0152] (II) Long-term toxicity test

[0153] According to the "Regulations on Drug Registration Management" and referring to the requirements of "Long-term Toxicity Test" in the "Technical Guidance for Long-term Toxicity Research of Traditional Chinese Medicine and Natural Medicine", the eye drops of the present invention were subjected to a long-term toxicity test on rabbits. The test was divided into 3 groups: a normal saline control group and a large and small dose group of eye drops, each group of 12 rabbits, half male and half female. The large and small dose groups of eye drops respectively used samples obtained by concentrating the eye drops prepared in Example 1 by 10 times and 3 times (that is, the drug concentrations were 10 times and 3 times the clinical concentrations set in Example 1 of the present invention, respectively). The treatment method is: administer eye drops to both eyes of the rabbit, once in the morning and evening, for 21 consecutive days. 1, 4, 24, 48, 72 hours after the first administration, no obvious irritation reaction was observed in the cornea, iris and conjunctiva of the normal saline control group and the large and small dose groups of eye drops, and the total score was 0. Observe the general signs of the rabbits daily and measure the body weight weekly. 24h after the last administration, 8 rabbits were selected from each group to test the scores of hematology, blood biochemistry, organ ratio, pathology and eye irritation. The results showed that after 21 days of administration, there was no significant difference in the body weight of the large and small doses of eye drops compared with the normal saline control group. There was no significant difference in hematological indicators: red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular content, mean corpuscular concentration, platelets, total white blood cell count, lymphocyte ratio, monocyte ratio, neutrophil ratio compared with the normal saline control group. The large and small doses of eye drops had no significant effect on blood biochemical indicators: serum alanine aminotransferase, aspartate aminotransferase, total protein albumin, creatinine, and urea nitrogen. The large and small doses of eye drops had no significant effect on the organ coefficients of the heart, liver, spleen, lung, and kidney. In pathological histological examination, there was no obvious toxic pathological change in the heart, liver, spleen, lung, and kidney compared with the normal saline control group. After 21 days of administration, no obvious irritation reaction was observed in the eyes of the normal saline control group. Among the 12 rabbits in the high-dose eye drops group, 2 rabbits had mild iris congestion and 2 rabbits had mild congestion of the conjunctiva; the total score was 4 points, and the average score was 0.33 points. Among the 12 rabbits in the low-dose eye drops group, 2 rabbits had mild iris congestion, with a total score of 2 points and an average score of 0.16 points. The average scores of the high-dose and low-dose eye drops groups were both lower than 0.5 points, and they were non-irritating according to the eye irritation reaction grading standard. During the recovery period (14 days after 21 days of administration), no obvious abnormalities were found in the body weight, hematological indicators, blood biochemical indicators and organ ratios of the high-dose and low-dose eye drops groups, and there was no significant difference compared with the normal saline control group. No obvious irritation reaction was observed in the cornea, iris and conjunctiva, and the total score was 0. The results show that the eye drops of the present invention have no obvious cumulative toxicity to domestic rabbits and are expected to be safe at clinical doses.

[0154] (III) Allergy test

[0155] 24 guinea pigs were randomly divided into 4 groups: low-dose eye drops group, high-dose eye drops group, negative control group and positive control group, with 6 in each group. The high-dose eye drops group was given the eye drops product prepared in Example 1, the low-dose eye drops group was given the liquid sample obtained by diluting the eye drops product prepared in Example 1 with 1 times of normal saline, the negative control group was given 0.9% sodium chloride injection, and the positive control group was given 10% ovalbumin normal saline solution. During sensitization, each group of guinea pigs was subcutaneously injected with 0.5 mL / guinea pig of the corresponding drug solution, administered once every other day, for a total of 5 injections. On the 13th day after the last administration, each group of guinea pigs was attacked by injecting 2 mL / guinea pig of the corresponding drug solution through the dorsal vein of the foot, and the changes in the guinea pigs within 30 minutes after administration were observed. The results showed that there was no obvious systemic active allergic reaction in the low-dose eye drops group and the high-dose eye drops group.

[0156] (IV) Hemolytic test

[0157] 2.5 mL of 2% immune red blood cell suspension was taken into a test tube, and 0.025-0.5 mL of the eye drops prepared in Example 1 was added respectively (8 groups of tests were set up, and the amount added in each test group was: 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.4, 0.5 mL), and the mixture was kept in a 37°C water bath for 3 hours, and the hemolysis of the immune red blood cell suspension in each test tube was observed. The results of naked eye observation showed that the immune red blood cell suspension with 0.025-0.1 mL of the eye drops did not show hemolysis, and the immune red blood cell suspension with 0.2-0.5 mL of the eye drops showed hemolysis. The absorbance of the rabbit erythrocyte suspension in each test tube was determined by ultraviolet spectrophotometry and the hemolysis rate was calculated. The results showed that the hemolysis rate of the rabbit erythrocyte suspension with 0.025-0.1 mL of eye drops was less than 5%, and the hemolysis rate of the rabbit erythrocyte suspension with 0.2-0.5 mL of eye drops was greater than 5%. The results suggest that high concentrations of eye drops have hemolytic effects and are not suitable for intravenous injection.

[0158] (V) Irritation test

[0159] Take 8 rabbits without eye irritation symptoms, corneal defects and conjunctival damage, half male and half female, and randomly divide them into an eye-moistening group and a negative control group, with 4 rabbits in each group. Within 24 hours before the test, check both eyes of each rabbit to confirm that there are no eye irritation symptoms, corneal defects and conjunctival damage, and then carry out the test treatment. The eye-moistening group is given the eye-moistening product prepared in Example 1, and the negative control group is given 0.9% sodium chloride injection. 0.1mL of the corresponding drug is dripped into the right eye of each rabbit, and then the eyelids are gently closed for about 10s, and the left eye is used as a control. Continuous administration for 7 days, 30, 60, 90, 120min before administration every day and 24, 48 and 72h after the last administration. Observe the reactions of the cornea, iris, conjunctiva, etc. with a magnifying glass, and record the reaction score. At the same time, observe the stimulation reactions such as conjunctival congestion, edema, photophobia and tearing, and score them. The results showed that the right eyes (administered) of each domestic rabbit had no irritation reaction in the cornea, iris, conjunctiva, etc., and there was no significant difference compared with the left eyes (not administered), that is, the eye drops of the present invention had no obvious eye irritation.

[0160] The results of the above acute toxicity test, long-term toxicity test, allergic test, hemolytic test and irritation test are summarized in Table 1.

[0161] Table 1 Summary of toxicology studies

[0162]

[0163] The eye drops prepared by the present invention are tested for their efficacy

[0164] The sources of animals and some drugs used in this experiment are as follows:

[0165] Rabbits and rats were obtained from the Department of Laboratory Animal Science, Peking University Health Science Center;

[0166] Normal saline was obtained from Sichuan Shule Pharmaceutical Co., Ltd.;

[0167] Carbomer eye drops were sourced from Beijing Bausch and Lomb Eye Care Products Co., Ltd.;

[0168] Epidermal growth factor eye drops were obtained from Shenzhen Huashengyuan Gene Engineering Development Co., Ltd.;

[0169] Atropine sulfate injection was obtained from Tianjin Jinyao Pharmaceutical Co., Ltd.;

[0170] Benzalkonium bromide solution was obtained from Beijing Feifan Pharmaceutical Co., Ltd.

[0171] 1. Effect of eye drops on tear secretion in rabbits

[0172] The tear secretion of normal rabbits was measured, and then 0.25 mL of 0.5 mg / mL atropine sulfate injection was injected into the lacrimal gland for shaping, and the tears were measured again after 1 hour of shaping. Group treatment was performed on the second day after shaping, and 40 rabbits were divided into 5 groups: negative control group, positive control group, low-dose eye drops group, medium-dose eye drops group, and high-dose eye drops group, with 8 rabbits in each group, among which the negative control group was given normal saline eye drops to rabbits, the positive control group was given 0.2% carbomer eye drops to rabbits, the low-dose eye drops group was given eye drops prepared in Example 2 to rabbits, the medium-dose eye drops group was given eye drops prepared in Example 1 to rabbits, and the high-dose eye drops group was given eye drops prepared in Example 3 to rabbits, 1 drop / time, 4 times / day, and the treatment lasted for 21 days. During the 21 days of treatment, atropine sulfate injection was injected into the lacrimal gland once a day, and the eye drops were immediately performed with the liquid after each injection. On the 7th, 14th and 21st days of treatment, tear secretion of rabbits was measured 1 hour after eye drops of the drug solution.

[0173] SPSS19 software was used to statistically analyze the tear secretion test results of rabbits before and after styling in each test group. The t test was used, and the values ​​were expressed as mean ± standard deviation to compare the significant differences. The results are shown in Table 2. The results show that after the lacrimal glands of rabbits were injected with atropine sulfate injection, the tear secretion of each test group was reduced compared with that before injection, with significant differences; moreover, there was no significant difference between the test groups before styling, and there was no significant difference between the test groups after styling; that is, the tear secretion of rabbits can be significantly reduced by injecting atropine sulfate injection into the lacrimal glands of rabbits, and there was no significant difference in the effect of atropine sulfate injection on reducing tear secretion among rabbits, so styling can be performed in this way.

[0174] Table 2 Rabbit tear secretion test results before and after modeling (mm) (n = 8)

[0175]

[0176] In Table 2, “*” indicates that p<0.05 compared with before styling

[0177] SPSS19 software was used to perform statistical analysis on the tear secretion test results of rabbits before treatment (i.e., after shaping) and on days 7, 14, and 21 after treatment in each test group. One-way analysis of variance was performed between the test groups, and the values ​​were expressed as mean ± standard deviation. The significant differences were compared, and the results are shown in Table 3.

[0178] Table 3 Results of tear secretion test before and after treatment in rabbits (mm) (n=8)

[0179]

[0180] In Table 3, “*” indicates p<0.05 compared with the negative control group

[0181] The results in Table 3 show that before treatment, there was no significant difference between the test groups; on the 7th day of treatment, the tear secretion of the medium-dose eye drops group, the high-dose eye drops group, and the positive control group increased compared with the negative control group, with a significant difference; on the 14th day of treatment, the tear secretion of the high-dose eye drops group increased compared with the negative control group, with a significant difference; on the 21st day of treatment, the tear secretion of the low-dose eye drops group, the medium-dose eye drops group, the high-dose eye drops group, and the positive control group increased compared with the negative control group, with a significant difference. On the 7th, 14th, and 21st days of treatment, there was no significant difference in the tear secretion of the positive control group and the low-dose eye drops group, the medium-dose eye drops group, and the high-dose eye drops group.

[0182] (II) Effect of eye drops on corneal damage and repair in rats

[0183] The tear glands of rats were surgically removed and 1% benzalkonium bromide solution was dripped into the eyes for shaping. The rats were divided into 5 groups for treatment for 21 days on the second day after shaping: negative control group, positive control group, low-dose eye drops group, medium-dose eye drops group, and high-dose eye drops group, with 16 rats in each group. The rats in the negative control group were given eye drops with normal saline, the rats in the positive control group were given eye drops with epidermal growth factor, the rats in the low-dose eye drops group were given eye drops with the eye drops prepared in Example 2, the rats in the medium-dose eye drops group were given eye drops with the eye drops prepared in Example 1, and the rats in the high-dose eye drops group were given eye drops with the eye drops prepared in Example 3, 1 drop / time, 4 times / day, and the treatment lasted for 21 days. The corneal lesions were examined and recorded on the 7th, 14th and 21st days. The degree of lesions was divided according to the following standards: no staining of the corneal epithelium, 0 points; staining area <25%, 1 point; staining area 25-50%, 2 points; staining area 50-75%, 3 points; staining area >75%, 4 points.

[0184] SPSS19 software was used to perform statistical analysis on the corneal lesions of rats in each experimental group before treatment and on days 7, 14 and 21 after treatment. The values ​​were expressed as mean ± standard deviation. One-way analysis of variance was performed among the experimental groups to compare the significant differences. The results are shown in Table 4.

[0185] Table 4 Results of corneal injury repair in rats (n=16)

[0186]

[0187] In Table 4, “*” indicates p<0.05 compared with the negative control group

[0188] The results of Table 4 show that before treatment, there was no significant difference in the lesions among the test groups. On the 7th day of treatment, the lesions in the high-dose eye drops group and the positive control group were significantly lighter than those in the negative control group; on the 14th day of treatment, the lesions in the low-dose eye drops group, the medium-dose eye drops group, the high-dose eye drops group, and the positive control group were significantly lighter than those in the negative control group; on the 21st day of treatment, the lesions in the low-dose eye drops group, the medium-dose eye drops group, the high-dose eye drops group, and the positive control group were significantly lighter than those in the negative control group. On the 7th, 14th, and 21st days of treatment, there was no significant difference in the lesions in the positive control group and the low-dose eye drops group, the medium-dose eye drops group, and the high-dose eye drops group. Epidermal growth factor is a factor in normal tears that promotes corneal epithelial repair, and epidermal growth factor eye drops are effective in repairing corneal epithelial damage; the eye drops of the present invention are rich in polysaccharides, amino acids, vitamins, carotene, flavonoids, chlorogenic acid, glycosides, and minerals, etc., which may be beneficial to the repair of corneal tissue.

[0189] Investigation of the preparation conditions of eye drops

[0190] The total polysaccharide content and the content of montmorillonine were used as indicators to investigate the three factors of water addition, decoction time and decoction times in step (2).

[0191] Eye drops were prepared according to the preparation method of Example 1, except that the amount of water added, decoction time and number of decoctions in step (2) were set according to the following Table 5. Then, the total polysaccharide content and the glycoside content in the prepared eye drops were determined according to the total polysaccharide content determination method (i.e., phenol-sulfuric acid method) and the glycoside content determination method (i.e., high performance liquid chromatography) described above. The results are shown in the following Table 5.

[0192] Table 5 Results of investigation on preparation conditions of eye drops

[0193]

[0194]

[0195] Investigating the raw materials of eye drops

[0196] (I) Investigation of the main ingredients

[0197] The eye drops were prepared according to the preparation method of Example 1, except that step (2) was changed to "add 12 times the amount of water to the residue obtained in step (1) and soak for 24 hours, then decoct for 3 times, each time for 1 hour, recover the decoction obtained in each decoction and combine them, filter the obtained decoction with a 40 mesh to recover the filtrate, and obtain the extract of the Chinese medicine composition (wolfberry and polygonatum)". Then, the content of lignoside in the prepared eye drops sample was determined according to the lignoside content determination method described above (i.e., high performance liquid chromatography), and the results are as follows: Figure 4 As shown. Figure 4 It can be seen that there is no chromatographic peak at the corresponding position of the chromatographic peak of the lignoserine reference substance in the HPLC of the sample; that is, the lignoserine components in the eye drops of the present invention are all derived from wild chrysanthemum, which is an indispensable Chinese medicinal material for preparing the eye drops of the present invention.

[0198] (II) Inspection of auxiliary materials

[0199] In view of the low water solubility of menthol, the present invention also adds a surfactant to the eye drops to increase the solubility of menthol in the liquid medicine, preferably Tween-80. The present invention investigates the dosage ratio of menthol and Tween-80, and the specific investigation method is as follows:

[0200] Take 1g of menthol, add 1, 2, 3, 4, 5, 6, 7, 8 times of Tween-80 respectively, add water to grind to dissolve the menthol, add to the filtrate obtained according to steps (1) and (2) of Example 1, and mix evenly; adjust the pH value of the mixed solution to 7.0-7.5 with 0.1mol / L NaOH solution and phosphate buffer successively; then add 8.5g NaCl to adjust the osmotic pressure to 280-290mOsm / L; and then add distilled water to 1000mL. Then place at room temperature for seven days, observe the dissolution of menthol, and thus determine the dosage ratio of menthol and Tween-80. The results are shown in Table 6. As can be seen from Table 6, when the dosage of Tween-80 is greater than or equal to 5 times the dosage of menthol, menthol has good solubility in eye drops.

[0201] Table 6 Dissolution of menthol in eye drops

[0202]

[0203] In Table 6: a means a large amount of precipitation, b means a small amount of precipitation, and c means no precipitation

[0204] It should be noted that the embodiments described above are only used to explain the present invention and do not constitute any limitation of the present invention. The present invention has been described with reference to the embodiments, but it should be understood that the words used therein are descriptive and explanatory words, rather than restrictive words. The present invention may be modified as specified within the scope of the claims of the present invention, and the present invention may be revised without departing from the scope and spirit of the present invention. Although the present invention described therein relates to specific methods, materials and embodiments, it does not mean that the present invention is limited to the specific examples disclosed therein, on the contrary, the present invention can be extended to all other methods and applications with the same functions.

Claims

1. A Chinese medicine composition for preparing eye drops, characterized in that: The traditional Chinese medicine composition consists of wolfberry fruit, polygonatum sibiricum, wild chrysanthemum and mint.

2. The Chinese medicine composition according to claim 1, characterized in that: In the traditional Chinese medicine composition, the weight portion of wolfberry is 10-15 parts, the weight portion of polygonatum is 10-15 parts, the weight portion of wild chrysanthemum is 8-12 parts, and the weight portion of mint is 0.01-0.2 parts in terms of menthol.

3. A Chinese herbal medicine extract for preparing eye drops, characterized in that: The Chinese medicine extract includes the extract of the Chinese medicine composition according to claim 1 or 2, preferably includes the water extract of wolfberry, the water extract of polygonatum, the water extract of wild chrysanthemum, and menthol.

4. The method for preparing the Chinese medicine extract according to claim 3, characterized in that: The method comprises refluxing 10 to 15 parts by weight of wolfberry and 10 to 15 parts by weight of polygonatum with 75 to 90% by volume ethanol to recover the drug residues, then boiling the recovered drug residues and 8 to 12 parts by weight of wild chrysanthemum with water to recover the drug liquid; finally, mixing the recovered drug liquid with 0.01 to 0.2 parts by weight of menthol to obtain the Chinese medicine extract; preferably, The solid-liquid ratio of the reflux is 1:(5-15), preferably 1:(8-12); and / or the number of reflux is 1-3 times; and / or the reflux time is 30-90 minutes each time; And / or, the solid-liquid ratio of the decoction is 1:(8-16), preferably 1:(10-15); and / or, the number of decoctions is 2-5 times, and recovering the medicinal liquid means recovering the medicinal liquid of each decoction and combining them; and / or, the decoction time is 30-90 minutes each time.

5. The preparation method according to claim 4, characterized in that: The specific processes of the method can be divided into three types, wherein process one includes the following steps: a. Take 10 to 15 parts by weight of wolfberry, 10 to 15 parts by weight of Polygonatum, mix well, then reflux with 75 to 90% by volume of ethanol, discard the reflux solution to retain the residue; b Take 8 to 12 parts by weight of wild chrysanthemum, wild chrysanthemum, water and the residue obtained in step a mixed, and then boiled to recover the liquid; c. The solution recovered in step b is mixed with 0.01 to 0.2 parts by weight of menthol to obtain a Chinese herbal extract; Process 2 includes the following steps: (a) taking 10 to 15 parts by weight of wolfberry, refluxing the wolfberry with 75 to 90% by volume ethanol, discarding the reflux solution and retaining the wolfberry residue; (b) taking 10 to 15 parts by weight of polygonatum sibiricum, refluxing the polygonatum sibiricum with 75 to 90% by volume ethanol, discarding the reflux liquid and retaining the polygonatum sibiricum residue; (c) taking 8 to 12 parts by weight of wild chrysanthemum, mixing the wild chrysanthemum, water, the wolfberry residue obtained in step (a), and the polygonatum residue obtained in step (b), then decocting and recovering the liquid medicine; (d) mixing the liquid medicine recovered in step (c) with 0.01 to 0.2 parts by weight of menthol to obtain a Chinese herbal medicine extract; Process three includes the following steps: a) taking 10 to 15 parts by weight of wolfberry, refluxing the wolfberry with 75 to 90% by volume ethanol, then discarding the reflux solution and retaining the medicinal residue to obtain the wolfberry medicinal residue; then adding water to the wolfberry medicinal residue for decoction, recovering the medicinal solution, and obtaining an aqueous extract of wolfberry; b) taking 10 to 15 parts by weight of polygonatum, refluxing the polygonatum with 75 to 90% by volume ethanol, discarding the reflux solution and retaining the residue to obtain polygonatum residue; then adding water to the polygonatum residue for decoction, recovering the liquid, and obtaining a water extract of polygonatum; c) taking 8 to 12 parts by weight of wild chrysanthemum, adding water to boil, recovering the medicinal liquid, and obtaining an aqueous extract of wild chrysanthemum; d) mixing the water extract of wolfberry obtained in step a), the water extract of polygonatum obtained in step b), and the water extract of wild chrysanthemum obtained in step c) with 0.01-0.2 parts by weight of menthol to obtain a traditional Chinese medicine extract.

6. The preparation method according to claim 4 or 5, characterized in that: The method further comprises crushing wolfberry and polygonatum before reflowing to obtain wolfberry coarse powder and polygonatum coarse powder; And / or, the method further comprises crushing the wild chrysanthemum before decocting to obtain wild chrysanthemum coarse powder; And / or, the method further comprises filtering the recovered drug solution, preferably, filtering using a 30-45 mesh screen; And / or, the method further comprises soaking the material to be decocted for 20 to 30 hours before decocting.

7. Use of the Chinese medicine composition according to any one of claims 1 to 2, the Chinese medicine extract according to claim 3, or the Chinese medicine extract prepared by the preparation method according to any one of claims 4 to 6 in the preparation of eye drops or medicaments for treating dry eyes.

8. An eye-lubricating liquid, characterized in that: The eye drops include the Chinese herbal extract according to claim 3 and / or the Chinese herbal extract prepared by the preparation method of any one of claims 4 to 6; preferably, the eye drops contain no less than 1.4 mg / mL of total polysaccharides, no less than 0.067 mg / mL of menthol, and a menthol concentration of 0.01 to 0.2 g / mL.

9. The eye-lubricating solution according to claim 8, characterized in that: The pH value of the eye drops is 7-7.8, and the osmotic pressure is 280-290 mOsm / L; And / or, the eye drops further include excipients; preferably, the excipients include any one or more of a surfactant, a pH regulator, an osmotic pressure regulator, and a buffer solution; more preferably, The surfactant is Tween-80; preferably, the concentration of Tween-80 in the eye drops is 0.08-2 g / mL, preferably 0.25-1 g / mL; more preferably, in the eye drops, the ratio of the concentration of Tween-80 to the concentration of menthol is greater than or equal to 5, preferably 5-10, more preferably 5-8; and / or The amount of the pH adjuster is the amount used to adjust the pH value of the eye drops to 7.0-7.5; preferably, the pH adjuster is sodium hydroxide or potassium hydroxide; more preferably, the concentration of sodium hydroxide or potassium hydroxide in the pH adjuster is 0.1 mol / L; and / or The concentration of the osmotic pressure regulator in the eye drops is the amount used to adjust the osmotic pressure of the eye drops to 280-290 mOsm / L; preferably, the osmotic pressure regulator is sodium chloride or potassium chloride; more preferably, the concentration of the osmotic pressure regulator in the eye drops is 8.0-9.0 g / mL; and / or The buffer solution is a phosphate buffer solution; preferably, the concentration of the phosphate buffer solution in the eye drops is an amount that can stabilize the pH value of the eye drops between 7.0 and 7.

5.

10. Use of the eye-lubricating solution according to claim 8 or 9 in the preparation of a medicament for treating dry eye.

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