Traditional Chinese medicine composition, pharmaceutical composition and preparation method and application thereof

Abstract

The invention relates to a traditional Chinese medicine composition, a pharmaceutical composition as well as a preparation method and application thereof, and the traditional Chinese medicine composition comprises the following raw materials in parts by mass: 3-15 parts of glossy privet fruit, 5-15 parts of semen cuscutae, 5-20 parts of semen cassiae, 3-13 parts of pipewort, 2-12 parts of scouring rush, 5-20 parts of radix paeoniae alba, 5-20 parts of radix puerariae and 5-15 parts of dendrobe. The pharmaceutical composition comprises the traditional Chinese medicine composition and nutrients, wherein the nutrients comprise one or more of a grape seed extract, fish oil powder and beta-carotene. After the components in the composition are reasonably combined, the composition has the advantages of being obvious in effect, lasting and stable in action and high in safety when being used for treating xerophthalmia; the traditional Chinese medicine composition can nourish liver and kidney, nourish blood and improve eyesight, clear heat and promote salivation, and regulate the functions of the body on the whole, and also can directly provide nutrient substances for eyes, improve the quality and quantity of tears, relieve eye inflammatory response, significantly relieve the symptom of xerophthalmia, and improve the living quality of patients.

Description

Technical Field

[0001] The present application relates to the field of medical technology, and in particular to a traditional Chinese medicine composition, a pharmaceutical composition, and a preparation method and application thereof. Background Art

[0002] Dry eye is a common eye disease, also known as keratoconjunctivitis sicca. It is a type of disease caused by abnormal tear quality or quantity or abnormal dynamics due to multiple factors, which causes decreased tear film stability and / or ocular surface damage, leading to ocular discomfort symptoms and visual dysfunction. The main clinical symptoms are dry eyes, pain or stinging, foreign body sensation, blurred vision, photophobia, eye fatigue, etc., which can affect patients' daily life and work in severe cases. The pathogenesis of dry eye is complex, involving multiple factors such as reduced tear secretion and decreased tear film stability. According to epidemiological surveys, the incidence of dry eyes in my country is 21% to 30%, with higher rates in women than in men and higher rates in the elderly than in the young.

[0003] Treatments for dry eye include the use of artificial tears, anti-inflammatory drugs, tear secretion-promoting drugs, and other drugs. There are many types of artificial tears, including aqueous, gel-like, and lipid-like types, which can replenish tears and temporarily relieve dry eye symptoms. Commonly used anti-inflammatory drugs include glucocorticoid eye drops and nonsteroidal anti-inflammatory drug eye drops. Glucocorticoid eye drops have strong anti-inflammatory effects, but long-term use may cause complications such as increased intraocular pressure and cataracts. Although nonsteroidal anti-inflammatory drug eye drops are relatively safe, they may also cause discomfort symptoms such as eye irritation. Oral drugs that promote tear secretion may cause sweating, gastrointestinal discomfort such as nausea, vomiting, and diarrhea; some drugs may also affect the cardiovascular system, causing palpitations, blood pressure fluctuations, etc. Topical tear secretion-promoting drugs may cause eye irritation, burning sensation, allergic reactions, etc. Therefore, there is an urgent need for effective drugs for the treatment of dry eye in clinical practice. Summary of the invention

[0004] Based on this, it is necessary to provide a traditional Chinese medicine composition, a pharmaceutical composition, and a preparation method and application thereof, which can significantly alleviate the symptoms of dry eye and improve the quality of life of patients.

[0005] The technical solution of this application is as follows:

[0006] The first aspect of the present invention provides a traditional Chinese medicine composition, which comprises the following raw materials, by weight: 3-15 parts of Ligustrum lucidum fruit, 5-15 parts of Cuscuta seed, 5-20 parts of Cassia seed, 3-13 parts of Herba Codonopsis pilosulae, 2-12 parts of Equisetum arvense, 5-20 parts of White Peony Root, 5-20 parts of Pueraria lobata and 5-15 parts of Dendrobium officinale.

[0007] In one embodiment, the Chinese medicine composition includes the following raw materials in parts by mass: 6-12 parts of Ligustrum lucidum, 8-12 parts of Cuscuta australis, 10-15 parts of Cassia seed, 6-10 parts of Herba Codonopsis pilosulae, 5-9 parts of Equisetum arvense, 10-15 parts of White Peony Root, 10-15 parts of Pueraria lobata and 8-12 parts of Dendrobium officinale.

[0008] The second aspect of the present invention provides a pharmaceutical composition, comprising the Chinese medicine composition as described above, and nutrients.

[0009] In one embodiment, the nutrients include one or more of grape seed extract, fish oil powder and beta-carotene.

[0010] In one embodiment, the grape seed extract refers to an extract having a proanthocyanidin content of ≥ 90%.

[0011] In one embodiment, the pharmaceutical composition comprises the following raw materials by weight:

[0012] 6-12 parts of Ligustrum lucidum fruit, 8-12 parts of Cuscuta seed, 10-15 parts of Cassia seed, 6-10 parts of Herba Codonopsis pilosulae, 5-9 parts of Herba Equisetum, 10-15 parts of White Peony Root, 10-15 parts of Pueraria lobata, 8-12 parts of Dendrobium officinale, 0.05-0.1 parts of Grape seed extract, 0.2-0.8 parts of fish oil powder and 0.005-0.01 parts of β-carotene.

[0013] The third aspect of the present invention provides a method for preparing the pharmaceutical composition as described above, comprising the following steps:

[0014] The raw materials in the Chinese medicine composition are mixed, boiled with water, filtered, concentrated, and dried to prepare a Chinese medicine extract powder;

[0015] The powder of the Chinese herbal extract and the nutrients are mixed to obtain the product.

[0016] The fourth aspect of the present invention provides use of the above-mentioned traditional Chinese medicine composition or the above-mentioned pharmaceutical composition in the preparation of a drug for treating dry eye.

[0017] In one embodiment, the drug is in the form of pills, powders, ointments, tablets, granules, lozenges, capsules, liquids or tinctures.

[0018] In one embodiment, the drug further comprises a pharmaceutically acceptable excipient;

[0019] Optionally, the pharmaceutically acceptable excipients include one or more of microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate.

[0020] Compared with the prior art, this application has the following beneficial effects:

[0021] The present application provides a Chinese medicine composition comprising Ligustrum lucidum, Cuscuta australis, Cassia seed, Herba Codonopsis pilosulae, Herba Equisetum, Paeonia lactiflora, Radix Puerariae and Dendrobium officinale. The Chinese medicine composition has the advantages of obvious effect, long-lasting and stable effect and high safety when used for treating dry eye after the various components are reasonably combined.

[0022] At the same time, the present application also provides a pharmaceutical composition comprising the above-mentioned Chinese medicine composition and nutrients, and the pharmaceutical composition has the following advantages:

[0023] (1) Multi-component synergistic treatment: The pharmaceutical composition of the present application organically combines traditional Chinese medicine with nutrients, and multiple components work synergistically to treat dry eye. It can nourish the liver and kidney, nourish blood and improve eyesight, clear away heat and promote the production of body fluid, regulate the body's functions as a whole, and directly provide nutrients to the eyes, improve the quality and quantity of tears, and reduce ocular inflammation, thereby significantly alleviating the symptoms of dry eye and improving the quality of life of patients. (2) High drug safety: The traditional Chinese medicines in the prescription are all commonly used traditional Chinese medicines, which have been verified by long-term clinical application and have high safety. Nutrients are also nutrients required by the human body and are safe and reliable to use at prescribed doses. In addition, the combination of traditional Chinese medicine and nutrients reduces the adverse reactions that may be caused by the high-dose use of a single drug, reduces the risk of side effects of the drug, and has a high safety of the overall formula, providing patients with a safe and effective treatment option. (3) Long-lasting and stable effect: The characteristic of the action of traditional Chinese medicine is to restore the body to a balanced state by regulating the internal environment of the body, thereby achieving the purpose of treating the disease. This overall regulatory effect has the characteristics of long-lasting stability and can improve the eye condition of patients with dry eye for a long time. At the same time, the supplementation of nutrients can also continuously provide nutritional support for the eyes, maintain the stability of the tear film and the normal metabolism of the eye tissue. Therefore, compared with some drugs that simply relieve symptoms, the pharmaceutical composition of the present invention has a more lasting therapeutic effect. (4) Wide range of applicable populations: The pharmaceutical composition of the present application is suitable for patients with various types of dry eye, whether it is dry eye caused by long-term excessive use of the eyes, or dry eye caused by liver and kidney yin deficiency in the middle-aged and elderly, and dry eye accompanied by eye inflammation. At the same time, for some patients who are not suitable for traditional Western medicine treatment or who have poor results with Western medicine treatment, a new and effective treatment option is provided. DETAILED DESCRIPTION

[0024] The present application will be further described in detail below in conjunction with specific embodiments. The present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thoroughly understood.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0026] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0027] As used herein, "pharmaceutically acceptable" refers to those ligands, materials, compositions, and / or dosage forms that are suitable for administration to a patient within the scope of sound medical judgment and commensurate with a reasonable benefit / risk ratio.

[0028] Herein, "pharmaceutically acceptable salt" refers to a salt suitable for use as a drug formed by any compound in the structure shown and an acid or base. Pharmaceutically acceptable salts include inorganic salts and organic salts. Among them, one type of salt is a salt formed by the compound of the present application and an acid. Acids suitable for forming salts include but are not limited to: inorganic acids such as hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, and naphthalenesulfonic acid; and amino acids such as proline, phenylalanine, aspartic acid, and glutamic acid. Another type of salt is a salt formed by the compound of the present application and a base. Suitable bases for forming salts include but are not limited to alkali metal salts (such as sodium salts or potassium salts), alkaline earth metal salts (such as magnesium salts or calcium salts), ammonium salts (such as lower alkanolammonium salts and other pharmaceutically acceptable amine salts), such as methylamine salts, ethylamine salts, propylamine salts, dimethylamine salts, trimethylamine salts, diethylamine salts, triethylamine salts, tert-butylamine salts, ethylenediamine salts, hydroxyethylamine salts, dihydroxyethylamine salts, trihydroxyethylamine salts, and amine salts formed from morpholine, piperazine, and lysine, respectively.

[0029] As used herein, "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. As used herein, the language "pharmaceutically acceptable carrier" includes buffers, sterile water for injection, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are compatible with drug administration. Each carrier must be "pharmaceutically acceptable" in the sense of being compatible with the other ingredients in the formulation and not harmful to the patient. Suitable examples include, but are not limited to: (1) sugars such as lactose, glucose and sucrose; (2) starches such as corn starch, potato starch and substituted or unsubstituted β-cyclodextrins; (3) cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository waxes; (9) oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn starch, etc. Rice oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffered saline; (21) other non-toxic compatible substances used in pharmaceutical preparations.

[0030] In the present invention, the "composition" may be a combination of a plurality of substances, and further, may be used in combination or may be a mixture of the combination.

[0031] The percentage content involved in the present invention, unless otherwise specified, refers to mass percentage for solid-liquid mixing and solid-solid mixing, and refers to volume percentage for liquid-liquid mixing.

[0032] As used herein, "one or more" refers to any one, any two, or any two or more of the listed items.

[0033] Herein, "further", "further", "particularly" and the like are used for descriptive purposes to indicate differences in content, but should not be construed as limiting the scope of protection of this application.

[0034] Herein, "first aspect", "second aspect", "third aspect", "fourth aspect", etc. are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. In addition, "first", "second", "third", "fourth", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of the present application, the meaning of "multiple" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined. In the description of the present application, the meaning of "several" is at least one, such as one, two, etc., unless otherwise clearly and specifically defined.

[0035] In this application, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0036] The percentage contents involved in this application, unless otherwise specified, refer to mass percentage for solid-liquid mixing and solid-solid mixing, and refer to volume percentage for liquid-liquid mixing.

[0037] The percentage concentrations mentioned in this application, unless otherwise specified, refer to the final concentration, which refers to the percentage of the added component in the system after the addition of the component.

[0038] The temperature parameters in this application, unless otherwise specified, allow both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. Fluctuations within the range of ±5°C, ±2°C, ±1°C, ±0.5°C, ±0.4°C, ±0.3°C, ±0.2°C, and ±0.1°C are allowed. Normal temperature or room temperature in this application refers to no temperature control operation, generally 4°C~35°C, preferably 20±5°C.

[0039] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0040] Dry eye syndrome is classified into the categories of "white and astringent syndrome", "dry and astringent syndrome", "divine water is about to dry up" and "dryness syndrome" in traditional Chinese medicine. Traditional Chinese medicine believes that the causes of dry eye syndrome mainly include the following aspects: Traditional Chinese medicine believes that the causes of dry eye syndrome include the six exogenous pathogens and internal injuries to internal organs. The six exogenous pathogens are mainly wind, dryness and fire, and the internal injuries to internal organs are closely related to the dysfunction of the liver, kidney, spleen, lung and other internal organs. Traditional Chinese medicine treatment of dry eye syndrome focuses on the overall concept and syndrome differentiation and treatment, and relieves symptoms by regulating the functions of internal organs and adopting a variety of treatment methods, such as acupuncture and acupoint massage, oral and external use of Chinese medicine, and other auxiliary methods such as qigong and scraping.

[0041] Based on this, the first aspect of the present invention provides a Chinese medicine composition, which includes the following raw materials by mass: 3-15 parts of Ligustrum lucidum, 5-15 parts of Cuscuta seeds, 5-20 parts of Cassia seeds, 3-13 parts of Coix seeds, 2-12 parts of Equisetum equisetum, 5-20 parts of White Peony Root, 5-20 parts of Pueraria lobata and 5-15 parts of Dendrobium officinale. Specifically, Ligustrum lucidum and Cuscuta seeds nourish the liver and kidney, improve the essence and eyesight, regulate the body's immune function and endocrine system, improve the liver and kidney yin deficiency state, thereby promoting the secretion of tears and the repair of eye tissue. Cassia seeds clear away heat and improve eyesight, moisten the intestines and relieve constipation, can clear the liver and purge fire, reduce the inflammatory response of the eyes, and at the same time, through the effect of moistening the intestines, eliminate the heat and toxins in the body, and indirectly improve the physiological environment of the eyes. Coix seeds and Equisetum equisetum evacuate wind-heat, improve eyesight and remove cataracts, can relieve wind-heat symptoms in the eyes, protect corneal and conjunctival tissues, and reduce ocular surface damage. White peony root nourishes blood and softens the liver, relieves acute pain, regulates blood circulation in the eyes, relieves discomfort symptoms such as dryness and pain in the eyes, and also has a certain antioxidant effect. Pueraria root relieves muscles and produces body fluid, raises yang and stops diarrhea, can dilate blood vessels in the eyes, improve blood circulation, increase nutrient supply to the eyes, and at the same time enhance yang and enhance the body's disease resistance. Dendrobium nourishes yin and clears heat, improves eyesight, nourishes stomach yin and kidney yin, allows body fluid to flow to the eyes, relieves symptoms such as dry eyes and fatigue, and can also clear away heat and improve eye discomfort caused by yin deficiency and internal heat. The above combination of Chinese medicinal materials has the effects of nourishing the liver and kidneys, nourishing the liver and improving eyesight, nourishing yin and clearing heat, and is suitable for the treatment of dry eyes.

[0042] In some of the examples, the Chinese medicine composition includes the following raw materials in parts by mass: 6-12 parts of Ligustrum lucidum, 8-12 parts of Cuscuta australis, 10-15 parts of Cassia seed, 6-10 parts of Herba Codonopsis pilosulae, 5-9 parts of Equisetum arvense, 10-15 parts of White Peony Root, 10-15 parts of Pueraria lobata and 8-12 parts of Dendrobium officinale.

[0043] Traditional Chinese medicine mainly improves eye symptoms by regulating the overall functions of the human body's internal organs, meridians, qi and blood, and acts on multiple systems and levels, but it does not cover local microscopic targets in the eye, such as nutrient transport at the cellular level, activation or inhibition of specific receptors, etc. It does not cover all aspects. If only traditional Chinese medicine is used for conditioning, it is necessary to wait for the body to restore its own intake, transformation and utilization of nutrients by regulating the functions of the spleen and stomach, liver and kidney storage of essence, and this process takes effect relatively slowly. The occurrence of dry eye is related to the lack of certain nutrients in the eye. If only traditional Chinese medicine is used for treatment, the supplementation of some specific nutrients required by the eye may not be timely and accurate enough. At the same time, there are some nutrient supplements for dry eye on the market, such as vitamin A, fish oil, etc. However, the supplementation of a single nutrient has limited effect, and it can often only play a role in a specific aspect of dry eye, and cannot comprehensively regulate the physiological function and metabolism of the eye.

[0044] Based on this, the second aspect of the present invention provides a pharmaceutical composition, comprising the Chinese medicine composition as described above, and nutrients.

[0045] In some of the examples, the nutrients include one or more of grape seed extract, fish oil powder and beta-carotene. Specifically, grape seed extract is rich in proanthocyanidins, has a strong antioxidant effect, can scavenge eye free radicals, reduce oxidative stress damage, and protect eye tissue from damage. At the same time, it can also inhibit inflammatory responses and improve eye microcirculation. Omega-3 fatty acids in fish oil powder have anti-inflammatory and lipid-regulating effects, which can reduce inflammatory responses in the eyes, improve the stability of the tear film, and promote eye health. Beta-carotene can be converted into vitamin A in the body. Vitamin A is essential for maintaining normal visual function, and its deficiency can lead to eye diseases such as dry eyes. Supplementation of beta-carotene can improve the nutritional status of the eyes and promote the normal metabolism and repair of eye tissues.

[0046] The Chinese medicine ingredients and nutrient ingredients work together to treat dry eyes. Chinese medicine regulates the body's functions as a whole, improves the liver and kidney yin deficiency, regulates the immune, endocrine and blood circulation systems, and creates good conditions for the absorption and utilization of nutrients; nutrients directly act on eye tissues, play antioxidant, anti-inflammatory, improve nutrient metabolism and other effects, and enhance the eye's defense and self-repair capabilities. The two work together to relieve the symptoms of dry eyes from multiple aspects, improve the treatment effect, and have the advantages of small side effects and long-lasting efficacy.

[0047] In some of these examples, the grape seed extract refers to an extract having a proanthocyanidin content of ≥90%.

[0048] In some of the examples, the content of Omega-3 fatty acids in the fish oil powder is ≥ 60%.

[0049] In some examples, the pharmaceutical composition includes the following raw materials in parts by mass:

[0050] 6-12 parts of Ligustrum lucidum fruit, 8-12 parts of Cuscuta seed, 10-15 parts of Cassia seed, 6-10 parts of Herba Codonopsis pilosulae, 5-9 parts of Herba Equisetum, 10-15 parts of White Peony Root, 10-15 parts of Pueraria lobata, 8-12 parts of Dendrobium officinale, 0.05-0.1 parts of Grape seed extract, 0.2-0.8 parts of fish oil powder and 0.005-0.01 parts of β-carotene.

[0051] The third aspect of the present invention provides a method for preparing the pharmaceutical composition as described above, comprising the following steps:

[0052] The raw materials in the Chinese medicine composition are mixed, boiled with water, filtered, concentrated, and dried to prepare a Chinese medicine extract powder;

[0053] The powder of the Chinese herbal extract and the nutrients are mixed to obtain the product.

[0054] In some examples, the total mass ratio of water to each raw material in the traditional Chinese medicine composition is (8-10): 1. It can be understood that the total mass ratio of water to each raw material in the traditional Chinese medicine composition includes but is not limited to 8: 1, 8.5: 1, 9: 1, 9.5: 1, 10: 1.

[0055] In some examples, the decocting time is 1 hour to 2 hours. It can be understood that the decocting time includes but is not limited to 1 hour, 1.2 hours, 1.4 hours, 1.6 hours, 1.8 hours, and 2 hours.

[0056] The fourth aspect of the present invention provides use of the above-mentioned traditional Chinese medicine composition or the above-mentioned pharmaceutical composition in the preparation of a drug for treating dry eye.

[0057] The technical personnel of the present application have found through a large number of studies that the composition of the present application has a good therapeutic effect on dry eye, including the improvement of tear secretion, corneal fluorescein staining score and tear film breakup time, which are better than the dry eye model control group; compared with the placebo, the symptom score of the test group was significantly reduced within 6 weeks, which shows that the pharmaceutical composition of the present application can effectively relieve dry eye symptoms, and the effect becomes more significant as the treatment time increases. Compared with the placebo, the test group significantly reduced the vision-related quality of life score, indicating that the composition of the present application has a significant effect in improving the visual function and quality of life of patients, so that patients have greatly improved in vision, eye comfort, etc., thereby improving the overall quality of life.

[0058] In some of these examples, the dosage form of the drug is a pill, powder, paste, tablet, granule, lozenge, capsule, liquid or tincture. It is understandable that the drug of the embodiment of the present application can be added with different pharmaceutically acceptable excipients to prepare a suitable clinical dosage form, which includes but is not limited to the dosage form described herein.

[0059] In some examples, the medicament further includes a pharmaceutically acceptable excipient.

[0060] In some examples, the pharmaceutically acceptable excipients include one or more of microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate.

[0061] In some of the examples, the mass ratio of microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate in the pharmaceutically acceptable excipient is (5-15): (0.5-1.5): (0.15-0.4). It can be understood that the mass ratio of microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate in the pharmaceutically acceptable excipient includes but is not limited to 5:1:0.25, 10:1:0.25, 15:1:0.25, 5:0.5:0.25, 5:1.5:0.25.

[0062] In some of these examples, the drug may be administered using a suitable route of administration based on clinical needs. It is understandable that the route of administration of the drug includes but is not limited to: intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration or transdermal administration.

[0063] The following is further described in conjunction with specific embodiments. The raw materials involved in the following specific embodiments, unless otherwise specified, can all be commercially available; the instruments used, unless otherwise specified, can all be commercially available; the processes involved, unless otherwise specified, are all routinely selected by those skilled in the art.

[0064] Some of the raw materials used in Examples 1 to 4 and Comparative Examples 1 to 3 are as follows:

[0065] Grape seed extract (proanthocyanidin content ≥90%) can be purchased from Shaanxi Snotech Biotechnology Co., Ltd.;

[0066] Fish oil powder (containing omega-3 fatty acids ≥ 60%) can be purchased from Xi'an Four Seasons Biotechnology Co., Ltd.;

[0067] β-Carotene can be purchased from Zhongda Hengyuan Biotechnology Co., Ltd.

[0068] The following are specific embodiments.

[0069] Example 1

[0070] Prescription: Ligustrum lucidum 10g, Cuscuta australis 10g, Cassia seed 12g, Herba Codonopsis pilosulae 8g, Equisetum equisetum 7g, White Peony 12g, Pueraria lobata 12g, Dendrobium candidum 10g, Grape seed extract (proanthocyanidin content ≥ 90%) 80mg, Fish oil powder (containing Omega-3 fatty acids ≥ 60%) 500mg, β-carotene 8mg.

[0071] Preparation method:

[0072] (1) Take Ligustrum lucidum fruit, Cuscuta seed, Cassia seed, Coix lacryma-jobi, Equisetum equisetum, White peony root, Pueraria root, and Dendrobium officinale, remove impurities, cut Coix lacryma-jobi, Equisetum equisetum, and Dendrobium officinale into sections, cut White peony root into thin slices, and cut Pueraria root into thick slices;

[0073] (2) Mix all the herbs evenly, add 8 to 10 times the amount of water and boil twice, each time for 1 to 2 hours, filter and combine the decoction;

[0074] (3) The decoction is concentrated under reduced pressure to an extract having a relative density of 1.2 to 1.4 (measured at 50°C to 60°C), and the extract is spray-dried to obtain a Chinese medicine extract powder;

[0075] (4) Evenly mix the Chinese herbal extract powder, grape seed extract, fish oil powder and β-carotene to obtain the product.

[0076] Example 2

[0077] Prescription: Ligustrum lucidum 6g, Cuscuta australis 12g, Cassia seed 15g, Herba Codonopsis pilosulae 6g, Equisetum equisetum 5g, White Peony 15g, Pueraria lobata 10g, Dendrobium candidum 12g, Grape seed extract (proanthocyanidin content ≥ 90%) 50mg, Fish oil powder (containing Omega-3 fatty acids ≥ 60%) 600mg, β-carotene 5mg.

[0078] Preparation method: Same as Example 1.

[0079] Example 3

[0080] Prescription: Ligustrum lucidum 12g, Cuscuta australis 8g, Cassia seed 10g, Herba Codonopsis pilosulae 10g, Equisetum equisetum 9g, White Peony 10g, Pueraria lobata 15g, Dendrobium candidum 8g, Grape seed extract (proanthocyanidin content ≥ 90%) 100mg, Fish oil powder (containing Omega-3 fatty acids ≥ 60%) 400mg, β-carotene 10mg.

[0081] Preparation method: Same as Example 1.

[0082] Example 4

[0083] Prescription: Ligustrum lucidum 9g, Cuscuta australis 11g, Cassia seed 13g, Herba Codonopsis pilosulae 7g, Equisetum equisetum 6g, Paeonia lactiflora 13g, Pueraria lobata 13g, Dendrobium candidum 8g, Grape seed extract (proanthocyanidin content ≥ 90%) 60mg, Fish oil powder (containing Omega-3 fatty acids ≥ 60%) 540mg, Beta-carotene 6mg.

[0084] Preparation method: Same as Example 1.

[0085] Comparative Example 1

[0086] This comparative example is a Chinese medicine composition only, without adding grape seed extract, fish oil powder, and β-carotene, and the details are as follows:

[0087] Prescription: Ligustrum lucidum 10g, Cuscuta australis 10g, Cassia seed 12g, Herba Codonopsis pilosulae 8g, Herba Equisetum 7g, Paeonia lactiflora 12g, Pueraria root 12g, Dendrobium candidum 10g.

[0088] Preparation method: Prepared in the same manner as in Example 1, after obtaining the Chinese medicine extract, add dextrin in an amount equal to the weight of the grape seed extract, fish oil powder and β-carotene in the prescription of Example 1, mix, and obtain the product.

[0089] Comparative Example 2

[0090] This comparative example is a nutrient composition only, which is as follows:

[0091] Prescription: Grape seed extract (proanthocyanidin content ≥ 90%) 100 mg, fish oil powder (containing Omega-3 fatty acids ≥ 60%) 600 mg, and β-carotene 10 mg.

[0092] Preparation method: Mix grape seed extract, fish oil powder and β-carotene evenly, add dextrin of the same weight as the Chinese medicine extract powder prepared in the prescription of Example 1, and mix to obtain the product.

[0093] Comparative Example 3

[0094] Prescription: Ligustrum lucidum 10g, Cuscuta australis 10g, Cassia seed 12g, Herba Codonopsis pilosulae 8g, Equisetum equisetum 7g, Paeonia lactiflora 12g, Pueraria root 12g, Dendrobium candidum 10g, Grape seed extract (proanthocyanidin content ≥ 90%) 100mg.

[0095] Preparation method: Prepared in the same manner as in Example 1, after obtaining the Chinese medicine extract, add the grape seed extract and mix evenly, then add the dextrin in an amount equal to the weight of the fish oil powder and β-carotene in the prescription of Example 1, mix, and obtain the product.

[0096] The drugs prepared in Examples 1 to 4 and Comparative Examples 1 to 3 were subjected to efficacy tests and voluntary human subject tests, as follows:

[0097] 1. Efficacy test

[0098] 1. Animal selection and grouping

[0099] Healthy C57BL / 6 mice, 8-10 weeks old, half male and half female, weighing 20g-25g, were selected. The mice were randomly divided into 9 groups, 10 mice in each group, namely:

[0100] Blank group: normal feeding, without any treatment;

[0101] Model control group: used to establish a dry eye model and give normal saline intervention to observe the natural development of the model and the influence of drug solvents;

[0102] The pharmaceutical composition group of the present invention: the pharmaceutical composition group of Examples 1 to 4;

[0103] Comparative example group of the present invention: Comparative example 1 to 3 drug groups.

[0104] All animal groups were fed adaptively for 1 week.

[0105] 2. Animal Model Establishment

[0106] The mouse dry eye model was established by subcutaneous injection of scopolamine combined with topical eye drops of benzalkonium chloride.

[0107] Scopolamine subcutaneous injection: Except for the normal control group, the mice in the other groups were subcutaneously injected with scopolamine (0.5 mg / kg) every day for 14 consecutive days. Scopolamine is a cholinergic receptor antagonist that can inhibit the secretion function of the lacrimal gland, resulting in reduced tear secretion.

[0108] Benzalkonium chloride topical eye drops: Except for the normal control group, all groups of mice were given 0.2% benzalkonium chloride solution in both eyes starting from the 5th day after scopolamine injection, 3 times a day, 2 μL each time, for 10 consecutive days. Benzalkonium chloride is a commonly used preservative that has a certain toxic effect on the ocular surface, which can destroy the integrity of ocular epithelial cells and cause ocular surface inflammation, thereby aggravating the symptoms of dry eye.

[0109] After continuous injection of scopolamine for 14 days and benzalkonium chloride eye drops for 10 days, the drugs were administered. The blank group was fed normally. The model group was gavaged with the same volume of saline. The drug groups of Examples 1 to 4 and Comparative Examples 1 to 3 were gavaged with the corresponding test drugs (the drugs were dissolved in saline to form solutions or suspensions). The doses of the drug groups of Examples and Comparative Examples were about 1.6 g / kg per day. The mice were fed with standard feed during the gavage administration, and were free to drink water and eat.

[0110] 3. Observation indicators and detection time points

[0111] Tear secretion measurement (Schirmer test): The test was performed before drug administration (i.e. after the model was successfully established but before drug administration), on the 7th, 14th, 21st, and 28th days of drug administration. A standard Schirmer test paper was used, one end of which was folded into a 5 mm long strip and gently placed at the junction of the middle and outer 1 / 3 of the lower eyelid conjunctival sac of the mouse to avoid contact with the cornea. The mouse remained in a natural state, and the test paper was removed after closing its eyes for 5 minutes, and the length of the filter paper wet was measured in millimeters (mm).

[0112] Corneal fluorescein staining score: The test was performed before administration, on the 14th day and the 28th day of administration. An appropriate amount of sodium fluorescein solution was dripped into both eyes of the mouse to make it evenly distributed on the corneal surface, and then the corneal staining was observed under a slit lamp. The score was given according to the range and degree of staining. The scoring criteria are as follows:

[0113] 0 points: There is no corneal staining, sodium fluorescein is evenly distributed, and the corneal surface is smooth and bright.

[0114] 1 point: There are less than 5 corneal staining spots, which are scattered and lightly stained.

[0115] 2 points: There are 5 to 10 corneal staining spots, which are slightly fused and have a moderate degree of staining.

[0116] 3 points: There are more than 10 corneal staining spots, which are obviously fused and appear in flakes or blocks, and the staining is darker.

[0117] 4 points: The corneal staining is extensive and dense, and the entire corneal surface is almost covered by the staining, accompanied by corneal edema or turbidity.

[0118] Tear breakup time (BUT): The test was performed before administration, on the 7th, 14th, 21st, and 28th day of administration. After the use of sodium fluorescein solution in the eye, the time when the first dry spot appeared on the corneal surface under the slit lamp was the tear film breakup time, in seconds (s). The measurement was repeated 3 times and the average value was taken.

[0119] 4. The results of the efficacy tests are shown in Tables 1 to 3.

[0120] Table 1 Tear secretion volume (mm) test results

[0121]

[0122] Table 2 Results of corneal fluorescein staining scoring test

[0123]

[0124] Table 3 Tear film breakup time measurement results (s)

[0125]

[0126] Note: * indicates P < 0.05 compared with the model control group; ** indicates P < 0.01 compared with the model control group.

[0127] The above data show that the pharmaceutical composition of Examples 1 to 4 of the present invention are superior to the model control group in terms of tear secretion, corneal fluorescein staining score and tear film breakup time, and most of the example groups also have significant advantages over the control group in the later period of administration, which preliminarily shows that the pharmaceutical composition of the present invention has a good therapeutic effect on dry eye. The control group also has an effect on dry eye related indicators to a certain extent, but the effect is not as significant as the pharmaceutical composition of the example group of the present invention.

[0128] 2. Voluntary participation of the population

[0129] 1. Screening of voluntary subjects

[0130] Age range: 18-65 years old, male or female. Meet the diagnostic criteria for dry eye, that is, have at least two of the following symptoms: dry eyes, sore eyes, eye fatigue, foreign body sensation, burning sensation, vision fluctuation, etc. or be diagnosed with dry eyes by ophthalmology examination in a hospital.

[0131] Exclusion criteria: patients with other eye diseases, such as glaucoma, cataracts, eye infections, corneal lesions, etc., patients with systemic diseases such as diabetes, thyroid disease, etc. that may affect tear secretion, patients who have received relevant treatment for dry eye in the past 3 months, patients who are allergic to any ingredient in the pharmaceutical composition of the present invention, pregnant women, lactating women or women who plan to become pregnant during the trial, patients with mental illness or cognitive impairment, and patients who cannot cooperate to complete the trial.

[0132] 2. Experimental drugs

[0133] Drug group: the composition of the present invention, prescription: Ligustrum lucidum 10g, Cuscuta australis 10g, Cassia seed 12g, Herba Codonopsis pilosulae 8g, Herba Equisetum 7g, Paeonia lactiflora 12g, Radix Puerariae 12g, Candida alba 10g, Grape seed extract (proanthocyanidin content ≥ 90%) 80mg, Fish oil powder (containing Omega-3 fatty acids ≥ 60%) 500mg, Beta-carotene 8mg.

[0134] Preparation method:

[0135] (1) Take Ligustrum lucidum fruit, Cuscuta seed, Cassia seed, Coix lacryma-jobi, Equisetum equisetum, White peony root, Pueraria root, and Dendrobium officinale, remove impurities, cut Coix lacryma-jobi, Equisetum equisetum, and Dendrobium officinale into sections, cut White peony root into thin slices, and cut Pueraria root into thick slices;

[0136] (2) Mix all the herbs evenly, add 8 to 10 times the amount of water and boil twice, each time for 1 to 2 hours, filter and combine the decoction;

[0137] (3) The decoction is concentrated under reduced pressure to an extract having a relative density of 1.2 to 1.4 (measured at 50 to 60°C), and the extract is spray-dried to obtain a Chinese medicine extract powder;

[0138] (4) Evenly mixing the Chinese herbal extract powder, grape seed extract, fish oil powder, and β-carotene;

[0139] (5) Add 10 g of microcrystalline cellulose, 1 g of sodium carboxymethyl starch, and 0.25 g of magnesium stearate, mix well, and press into tablets using a tablet press.

[0140] Positive control group: Qiju Dihuang Concentrated Pills (commercially available finished product), taken orally, 8 pills each time, 3 times a day.

[0141] Placebo group: Placebo tablets, which are exactly the same in appearance, shape, color and size as those of the experimental group, but do not contain active drug ingredients and are composed of starch, dextrin, food coloring, flavoring, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate.

[0142] A total of 60 volunteers were recruited and randomly divided into 3 groups, with 20 in each group. The drug group took 1 dose per day, half an hour after breakfast, lunch and dinner, and the positive control group took 8 pills of Qiju Dihuang Concentrated Pills orally, 3 times a day. The placebo group took the same amount of placebo as the drug group orally each time, and each group took it for 6 consecutive weeks.

[0143] 3. Effectiveness indicator evaluation

[0144] Dry eye symptom score: A questionnaire survey was conducted before the trial, and in the second, fourth, and sixth weeks of the trial. The subjects were asked to score the severity of dry eye symptoms (dry eyes, astringent eyes, eye fatigue, foreign body sensation, burning sensation, visual fluctuations, etc.) on a scale of 0-4, with 0 indicating no symptoms, 1 indicating mild symptoms, 2 indicating moderate symptoms, 3 indicating severe symptoms, and 4 indicating very severe symptoms. The sum and average scores of the symptom scores were calculated to evaluate the improvement of the drug on dry eye symptoms.

[0145] Vision-related quality of life score (VR-QoL): The subjects were evaluated before and at the end of the trial using the Ocular Surface Disease Index (OSDI) questionnaire. The questionnaire covers aspects such as vision and the impact of ocular discomfort symptoms on daily life. The total score is 48 points, and the higher the score, the worse the vision-related quality of life. The effect of the drug on the quality of life of the subjects was evaluated by comparing the changes in scores before and after the drug trial.

[0146] 4. The results of efficacy evaluation are shown in Tables 4 and 5.

[0147] Table 4 Dry eye symptom scores

[0148]

[0149] Note: * indicates P < 0.05 compared with the placebo group; ** indicates P < 0.01 compared with the placebo group.

[0150] The results showed that compared with the placebo, the symptom scores of the drug trial group were significantly reduced within 6 weeks, which indicates that the pharmaceutical composition of the present invention can effectively relieve dry eye symptoms, and the effect becomes more significant as the treatment time increases. The symptom scores of the positive control group were also significantly reduced during the trial period, but the overall improvement was weaker than that of the drug trial group.

[0151] Table 5 Visually related quality of life score (OSDI)

[0152]

[0153] Note: * indicates P < 0.05 compared with the placebo group; ** indicates P < 0.01 compared with the placebo group.

[0154] The results showed that compared with the placebo, the drug test group significantly reduced the visual-related quality of life score, indicating that the composition of the present invention has a significant effect on improving the visual function and quality of life of patients, and has greatly improved the patients' vision, eye comfort, etc., thereby improving the overall quality of life. The positive control group has a certain improvement effect on the patients' visual-related quality of life, but the effect is weaker than that of the drug test group.

[0155] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0156] The above-described embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be construed as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent application shall be subject to the attached claims, and the description may be used to interpret the content of the claims.

Claims

1. A Chinese medicine composition, characterized in that: The invention comprises the following raw materials by weight: 3-15 parts of Ligustrum lucidum fruit, 5-15 parts of Cuscuta seed, 5-20 parts of Cassia seed, 3-13 parts of Herba Codonopsis pilosulae, 2-12 parts of Herba Equisetum, 5-20 parts of White Peony Root, 5-20 parts of Puerariae Radix and 5-15 parts of Dendrobium officinale.

2. The Chinese medicine composition according to claim 1, characterized in that: The invention comprises the following raw materials by weight: 6-12 parts of Ligustrum lucidum fruit, 8-12 parts of Cuscuta seed, 10-15 parts of Cassia seed, 6-10 parts of Herba Codonopsis pilosulae, 5-9 parts of Herba Equisetum, 10-15 parts of White Peony Root, 10-15 parts of Puerariae Radix and 8-12 parts of Dendrobium officinale.

3. A pharmaceutical composition, characterized in that It comprises the Chinese medicine composition according to claim 1 or 2, and nutrients.

4. The pharmaceutical composition according to claim 3, characterized in that The nutrients include one or more of grape seed extract, fish oil powder and beta-carotene.

5. The pharmaceutical composition according to claim 4, characterized in that The grape seed extract refers to an extract with a proanthocyanidin content of ≥90%.

6. The pharmaceutical composition according to claim 4, characterized in that In parts by mass, it includes the following raw materials: 6-12 parts of Ligustrum lucidum fruit, 8-12 parts of Cuscuta seed, 10-15 parts of Cassia seed, 6-10 parts of Herba Codonopsis pilosulae, 5-9 parts of Herba Equisetum, 10-15 parts of White Peony Root, 10-15 parts of Pueraria lobata, 8-12 parts of Dendrobium officinale, 0.05-0.1 parts of Grape seed extract, 0.2-0.8 parts of fish oil powder and 0.005-0.01 parts of β-carotene.

7. A method for preparing the pharmaceutical composition according to any one of claims 3 to 6, characterized in that: The steps include: The raw materials in the Chinese medicine composition are mixed, boiled with water, filtered, concentrated, and dried to prepare a Chinese medicine extract powder; The powder of the Chinese herbal extract and the nutrient are mixed to obtain the product.

8. Use of the traditional Chinese medicine composition according to claim 1 or 2 or the pharmaceutical composition according to any one of claims 3 to 6 in the preparation of a drug for treating dry eye.

9. The use according to claim 8, characterized in that: The dosage form of the medicine is pill, powder, paste, tablet, granule, lozenge, capsule, liquid or tincture.

10. The use according to claim 8, characterized in that: The drug also includes pharmaceutically acceptable excipients; Optionally, the pharmaceutically acceptable excipients include one or more of microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate.

Images