CN116920027A - Traditional Chinese medicine composition for treating cataract caused by liver-kidney yin deficiency and qi and blood stasis, and preparation method and quality control method thereof - Google Patents
Traditional Chinese medicine composition for treating cataract caused by liver-kidney yin deficiency and qi and blood stasis, and preparation method and quality control method thereof Download PDFInfo
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Abstract
The invention discloses a traditional Chinese medicine composition for treating cataract caused by yin deficiency of liver and kidney and qi and blood stasis, a preparation method and a quality control method thereof. The traditional Chinese medicine composition is prepared from the following raw materials: fructus Lycii, fructus Ligustri Lucidi, rehmanniae radix, semen Cassiae, flos Chrysanthemi, and Achyranthis radix. The preparation process of the wolfberry fruit and the cassia seed in the composition is deeply ploughed and carefully done on the basis of the prior art means, the preparation method and the quality control method of the composition with stable process and good reproducibility are obtained in the aspects of the transfer rate, the extraction rate and the like of the active ingredients, besides the content of chrysophanol in the composition is evaluated, the content of the active ingredients of lutein and the polysaccharide of the cassia seed is evaluated at the same time, the extraction rate and the transfer rate of the active ingredients are further improved through innovation of the preparation method of a plurality of ingredients in the composition, the effect of improving the clinical effective rate by 96.67 percent is obtained, the effective rate is improved by 16 percent compared with the conventional preparation method, and the traditional Chinese medicine composition can achieve the effective treatment effect on early-stage cataract patients and middle-stage cataract patients.
Description
Technical Field
The invention relates to a traditional Chinese medicine composition for treating cataract with the symptoms of liver-kidney yin deficiency and qi and blood stasis, a preparation method and a quality control method thereof. The invention belongs to the technical field of medicines.
Background
The modern society has fast life rhythm and high pressure, and people are easy to cause cerebral nerve dysfunction, thereby causing emotional disorder, hurting liver and kidney, and qi stagnation, and further causing various diseases by liver and kidney yin deficiency. The old people with spleen and stomach hypofunction often have the defects of ingestion and qi and blood biochemical insufficiency, and can affect liver and kidney functions. Most importantly, the daily level of life of modern people is improved, the food intake of high calories is increased, and the substances are spicy and hot when being addicted to cigarette and wine, and have warm and dry nature, and are easy to burn and consume liquid, and damage yin and fluid. Leading to an increasing number of patients suffering from cataract due to deficiency of liver-yin and kidney-yin and glaucoma. Cure and resolution of such afflictions is critical.
The increasing number of cataract patients caused by yin deficiency of liver and kidney can lead to vision deterioration of the patients, and the transparent crystals in the human eyes can be turbid. Early cataract onset, and its associated symptoms are not obvious. Generally, the visual blur is slightly seen, and thus the attention of a patient is difficult to be paid. The patient may be mistaken for eyestrain or presbyopia without going to a hospital visit. Patients in the middle of cataract onset have more cloudy lenses, form more blurred vision, and may cause abnormal symptoms such as glare, myopia, strabismus, etc. After the condition is more serious, cataract patients may even lose sight. The disease has long disease course, is mainly seen in old patients, has two means of operation treatment and drug treatment for the treatment of the old patients, and is suitable for drug treatment if the disease is early; if the disease is chronic and nebula, but three lights are still visible, surgery is preferable; if the crystal beads are grey and turbid, the pupil spirit is obviously obstructed, the medicine treatment is difficult to work, and the operation treatment is carried out after the nebula is fixed and the obstacle is aged.
The recipe is called "round nebula" as cataract. One of the round nebula and the internal disorder is first found in "Peronous ophthalmic Dragon Lun", but the treatment of this disease is recorded as earliest in "external Tai Mi Yao". The book "eye disease" is: the eyes are caused by no cause, suddenly feel the membranous, are not painful and itching, are gradually unknown, and are lost after the years of age. The eyes are different in appearance, but only in the small beads, the eyes are blocked, and the eyes are bluish white, and the eyes are clear of bright and dark lights, and the eyes are clear of the eyes. Thus, it is called as brain flow blind eye. When the eyes are not affected, fly black seeds are seen before the eyes are carelessly, and the eyes are gradually moved up and down, so the Jinzhi formula is preferred. After one needle, the clouds are broken and the sun is seen. The ancient people misused the disease to be blindness due to the formation of a cataract caused by cerebral lipid flow, so the disease is called cerebral flow blue blindness. Although the perspective is wrong, the Jin Bijue, namely the earliest ophthalmic surgery treatment operation, namely the needle barrier removal operation, is the earliest record of the ophthalmic needle barrier removal operation in the traditional Chinese medicine literature, and lays clinical and theoretical foundation for the development of the ophthalmic surgery technology of the later-generation traditional Chinese medicine.
The syndrome differentiation and the syndrome differentiation are combined, and the whole body and the local are associated, so that the principle of treating both principal and secondary aspect of disease is established, and the syndrome of the recipe (the eyesight improving and kidney nourishing tablet) is liver-kidney yin deficiency and qi and blood stasis. "Lingqiu-Tiannian" is: fifty years old, liver qi failing, liver leaves thin, bile going out and eyes going unclear. "deficiency of liver-yin and kidney-yin, deficiency of essence and blood, malnutrition of eyes, and blurred vision due to gradual mixing of crystal beads; kidney governs bone, kidney stores essence, essence and produces marrow, and marrow belongs to brain, liver and kidney yin deficiency, brain marrow and bone malnutrition, so dizziness, tinnitus, soreness and weakness of waist and knees. A red tongue with thin coating and a thin pulse is a pattern of yin deficiency. Malnutrition of the eyes, obstruction of blood vessels and stagnation of qi and blood stasis are caused by long-term malnutrition of the eyes. Therefore, it is indicated for liver and kidney, and also has the actions of resolving stasis, resolving hard mass and improving vision.
Patent application publication No. CN1456296A discloses a granule for improving eyesight and nourishing kidney and a preparation method thereof; the patent application with publication number of CN1548090A discloses a pill for improving eyesight and nourishing kidney and a preparation method thereof, the contents of the two patents are respectively granules and pills, the formula, the preparation method and the clinical curative effect are different from those of the pill, and the pill is inconvenient for patients to carry and take, and meanwhile, the preparation method is easy to cause the degradation of lutein serving as an active ingredient in wolfberry fruit; and the cassia seed extract can cause a great deal of loss due to viscosity, so that the transfer rate of the active ingredient chrysophanol is lower, and the treatment effect of the medicine is affected. Meanwhile, the glossy privet fruit is directly crushed to prepare the preparation, and fat grease in medicinal materials of the preparation is easy to cause difficult tabletting and forming, so that friability and disintegration time are influenced, and product quality is influenced.
Disclosure of Invention
The invention aims to provide a traditional Chinese medicine composition for treating cataract caused by deficiency of liver-yin and kidney-yin and stagnation of qi and blood, a preparation method and a quality control method thereof.
In order to achieve the above purpose, the invention adopts the following technical means:
the invention relates to a traditional Chinese medicine composition for treating cataract caused by yin deficiency of liver and kidney and qi and blood stasis, which is prepared from the following raw materials in parts by weight:
100-500 parts of medlar, 100-400 parts of glossy privet fruit, 50-300 parts of rehmannia, 50-220 parts of cassia seed, 50-250 parts of chrysanthemum and 30-150 parts of achyranthes root.
Preferably, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:
400 parts of medlar, 300 parts of glossy privet fruit, 200 parts of rehmannia, 220 parts of cassia seed, 200 parts of chrysanthemum and 100 parts of achyranthes root. Or alternatively
The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:
200 parts of medlar, 150 parts of glossy privet fruit, 100 parts of rehmannia, 100 parts of cassia seed, 100 parts of chrysanthemum and 50 parts of achyranthes root.
The Chinese wolfberry fruit, fructus Lycii, sweet and flat. It enters liver, kidney and lung meridians. Nourishing liver and kidney, replenishing essence and blood, improving eyesight and the highest dosage. Essence and blood are the material basis of kidney yin and kidney yang, and medlar nourishes liver and kidney essence and blood, and essence and blood are sufficient to nourish yin of liver and kidney. Such as "Ben Cao Jing Ji Zhi" (materia Medica of concentrated injection): "tonify essence and Qi, strengthen vagina". "the Chinese wolfberry fruit, fructus Lycii, with good effect of improving eyesight, can be used for treating dim eyesight and hypopsia caused by deficiency of liver and kidney essence and blood, and is an essential herb for ophthalmology, so it is" improving eyesight "in Ben Cao gang mu". Glossy privet fruit, fructus Ligustri Lucidi, sweet, bitter and cool. It enters liver and kidney meridians. Tonify liver and kidney, clear deficiency heat and improve vision. The glossy privet fruit is sweet in flavor, can nourish yin of liver and kidney, is bitter and cool, can clear deficiency heat, is especially good at treating the symptoms of yin deficiency and fever of liver and kidney, and is a good product for clearing and nourishing because the tested product is nourishing but not greasy and is cool in nature. For cold syndrome of kidney-yang, it is a key herb for clearing heat and replenishing essence, with its flavor and smell of yin. In addition, the glossy privet fruit has the effect of improving eyesight and is used for treating the vision decline and the dim eyesight caused by the deficiency of liver-yin and kidney-yin. Such as "Ben Cao Bei Yao": "benefit liver and kidney, calm five viscera, strengthen waist and knee, improve ear and eye, blacken beard and hair, tonify wind deficiency, and remove hundred diseases. Both of them are good drugs for improving eyesight, and they are homologous to each other in terms of liver and kidney, and supplement each other in terms of essence and blood, both liver and kidney and yin. Fructus Lycii to obtain fructus Ligustri Lucidi, the tonifying effect is increased; the fruit of glossy privet is good at relieving fever due to yin deficiency because it is good at relieving dryness. In the recipe, rehmannia root is sweet, bitter and cold. It enters heart, liver and kidney meridians. Clear heat and cool blood, nourish yin and promote the production of body fluid. For long time, yin deficiency generates heat, so the dried rehmannia root, dried orange peel, fructus Ligustri Lucidi is used to treat deficiency heat together with the actions of clearing heat and nourishing yin, and reinforcing the tonifying effect. The three herbs complement each other and the phase is indicated for the root cause of yin deficiency of liver and kidney. For long-term yin deficiency of liver and kidney, yin failing to control yang and causing hyperactivity of liver yang, chrysanthemum and cassia seed are used to calm liver yang, clear liver and improve vision. Chrysanthemum is pungent, sweet, bitter and slightly cold. It enters liver and lung meridians. Clear heat, calm liver and improve vision. Chrysanthemum and Lycium chinense are combined to clear heat, nourish liver and improve vision. Semen Cassiae is sweet, bitter and slightly cold. Enter liver and large intestine meridians. Clear liver and improve vision, moisten intestines and relieve constipation. It is indicated for constipation due to liver heat and also gives heat evil out of the way. Chrysanthemum and semen Cassiae are both indicated for the syndrome of liver yang hyperactivity by clearing heat and pacifying liver. Achyranthes root, radix Achyranthis bidentatae, bitter and sour, and it is flat. It enters liver and kidney meridians. Promoting blood circulation, removing blood stasis, tonifying liver and kidney, strengthening tendons and bones, promoting urination and treating stranguria. For the long-term malnutrition of eyes, the blood vessels are not smooth and qi and blood stasis is blocked, so it is combined with niu xi to activate blood and remove stasis, tonify liver and kidney and strengthen tendons and bones. It is good at descending because it can tonify by walking in Ben Cao Jing Shu. In addition, niu xi Shang Shangke has the actions of inducing diuresis to treat stranguria, inducing diuresis and promoting blood circulation to remove blood stasis.
The whole prescription has six herbs, so the herbs are less powerful and obvious in main and secondary aspects. It has the effects of nourishing liver and kidney, improving eyesight, resolving hard mass, and removing blood stasis. Supplement each other and act appropriately, so it is indicated for cataract due to deficiency of liver-yin and kidney-yin and qi and blood stasis.
In addition, this recipe can also be used to treat five wind internal obstruction (glaucoma) due to hyperactivity of liver yang. Glaucoma is an eye disease which causes damage to the disk and visual field defect and even blindness due to pathological ocular hypertension, and corresponds to liver-yang hyperactivity which is a five-wind internal barrier in the traditional Chinese medicine. Glaucoma belongs to the category of five wind internal barrier (green wind, yellow wind, black wind and black wind), lei Tou wind and head deflection wind in traditional Chinese medicine. Ancient people named wind indicated that the disease was severe, pain was severe, and the changes were rapid and the harm was severe. Five wind types are classified according to etiology and clinical manifestations. "great formation of mesh: the symptoms are wind, fire and phlegm, the diseases are in strong cross attack, headache and eye pain are acute, jin Jingxian is dispersed, and then the spirit and water appear a certain color along with a certain viscera, namely five wind. "the" Yizongjin Jian-ophthalmic heart law key formula "says that: the pupil turns yellow, which is named yellow wind; the person turning green and white is named as green wind; the person turning black is named as black wind; the person who turns red is named as wufeng; the person who turns cyan is called cyan wind. Since the five pupils have the changes of size and color and the later stage has the clouding of crystal beads, they are all in the category of internal obstruction, so they are called five wind internal obstruction. Lei Tou wind and migraine wind both have severe headache, including headache caused by ocular diseases, such as glaucoma, or ocular diseases caused by headache. Liver fire can generate wind, liver yang can dispel wind, liver opens into eyes, so the occurrence and development of the disease are most closely related to liver. Since mydriasis belongs to kidney and liver and kidney are homologous, qi and blood disharmony, adverse effect of eyes and orifices and accumulation of water and spirit can be caused by excessive liver and kidney wind-fire, liver and kidney yin-yang, qi stagnation of liver and spleen and internal generation of turbid phlegm. Ancient people also noted local factors of this disease, wang, foreign secret, volume twenty-one eye diseases, different climates, say: the sources of this disease are the same as those caused by the deficiency of the internal hepatic duct and the eye obstruction. The five wind internal disorder treated by the recipe (MINGMUZISHEN tablet) is yin deficiency and yang hyperactivity type. Yin deficiency of liver and kidney, hyperactivity of yang-qi, wind-transforming into liver-yang, ascending of wind-yang, disturbance of qi and blood stasis, headache, eye distention, hard eyes, dizziness and tinnitus. Yin is astringing, yang is dispersing, yin deficiency and yang hyperactivity cause mydriasis and deficiency of yin and blood are small, and mydriasis is malformed. Deficiency of liver-yin and kidney-yin, deficiency of essence and blood, amnesia and insomnia due to malnutrition of brain, soreness of waist and knees due to malnutrition of bones. The yin fluid cannot be applied to the mouth, and the mouth is dry and the pharynx is dry. The tongue pulse also manifests as yin deficiency. In the recipe, ju Hua and Jue Ming can calm liver yang and treat liver yang hyperactivity (symptoms caused by high eye pressure), which means to treat the disease by differentiation.
Furthermore, the invention also provides application of the traditional Chinese medicine composition in preparing a medicine for treating cataract caused by deficiency of liver-yin and kidney-yin and stagnation of qi and blood.
Still further, the invention also provides a method for preparing the traditional Chinese medicine composition, which comprises the following steps:
extracting and concentrating
1) Extraction of wolfberry fruit
Crushing the wolfberry fruit clean medicinal material with the crushing rate of 75%, weighing wolfberry fruit according to the weight parts, placing the wolfberry fruit clean medicinal material into a clean container, adding ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank, adding a large-aperture screen mesh wrapped by 100-mesh silk cloth at the bottom of the percolation tank, surrounding the periphery by using absorbent cotton surrounding pads, adding ethanol with the weight of 1.5 times of 60% v/v, discharging air in the medicinal material, capping, and soaking for 24 hours; percolating at a speed of 3.5ml/min/kg per minute until 60% v/v ethanol is added and percolating is completed, collecting percolate, and performing light-shielding operation in the whole process of percolating;
placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum until the vacuum degree rises to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35, collecting paste, and sealing for later use;
2) Rehmannia root and achyranthes root extraction
Weighing rehmannia root slices and achyranthes root sections according to the weight parts, putting the rehmannia root slices and achyranthes root sections into an extraction tank, adding 10 times of drinking water by weight for the first time, and starting steam heating. When the liquid medicine in the extraction tank boils, extracting for 2 hours, and filtering the liquid medicine by using 200-mesh filter cloth; adding 10 times of drinking water, extracting for 1.5 hr, filtering with 200 mesh filter cloth, and discarding residue;
mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator; starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of a first sight glass in a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator to concentrate the extract to a relative density of 1.28-1.30, and collecting the extract for later use, wherein the first-effect temperature is 75-85 ℃, and the second-effect temperature is 65-75 ℃;
3) Semen Cassiae extract
Weighing semen cassiae according to the parts by weight, tearing and crushing the clean semen cassiae by a pair of rollers to split the clean semen cassiae into two parts, putting the two parts into an extraction tank, adding 10 times of drinking water by weight for the first time, extracting for 2 hours, centrifugally filtering the liquid medicine by a flat filter, grinding and crushing the medicinal residues, putting the medicinal residues into the extraction tank again, adding 8 times of drinking water by weight for the second time, extracting for 1.5 hours, filtering the medicinal residues by a 200-mesh filter cloth, and discarding the medicinal residues;
Mixing the above two filtrates, concentrating in a double-effect energy-saving evaporation concentrator, and starting a vacuum pump until the first-effect vacuum degree rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of a first sight glass in a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator to concentrate the extract to a relative density of 1.28-1.30, and collecting the extract for later use, wherein the first-effect temperature is 75-85 ℃, and the second-effect temperature is 65-75 ℃;
4) Chrysanthemum extraction
And (3) weighing chrysanthemum according to the weight parts, putting the chrysanthemum into a traditional Chinese medicine extraction tank, and adding drinking water for extraction twice. Adding 10 times of drinking water by weight for the first time, starting steam heating, circulating for 5 minutes when the temperature of the liquid medicine in the extraction tank reaches 70-75 ℃, regulating steam pressure to keep the liquid medicine at 70-75 ℃, leaching for 1.5 hours, and filtering the liquid medicine by using 200-mesh filter cloth; adding 8 times of drinking water, leaching for 1 hr, filtering the medicinal liquid with 200 mesh filter cloth, and discarding residue; mixing the two filtrates, concentrating in a double-effect energy-saving evaporation concentrator, and starting a vacuum pump until the first-effect vacuum degree rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating to the relative density of 1.28-1.30, and collecting the clear paste for later use;
(II) formulations
1) Crushing
Pulverizing fructus Ligustri Lucidi into fine powder with 100 mesh stainless steel screen in pulverizer;
2) Mixing, granulating, drying, and grading
Placing pregelatinized starch and fructus Ligustri Lucidi fine powder into a rapid stirring granulator, mixing at high speed for 5 min to make the mixture uniform, sieving with 60 mesh sieve, placing into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract uniformly, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after the spraying, drying to air inlet temperature less than 65deg.C, discharging, sieving with 20 mesh sieve, granulating, and collecting granule;
3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use;
4) Tabletting
Tabletting the mixed granules, wherein each tablet weighs 0.62g, and the difference of tablet weights is ensured to be within the range of 0.62g plus or minus 5.0%;
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
Preferably, the preparation method further comprises a quality control method for the traditional Chinese medicine composition, and the method comprises the following steps:
(one) authentication detection
1) Identification of semen Cassiae
Taking 10 pieces of a test sample, removing a film coating, grinding, adding 20ml of methanol, soaking for 1 hour, carrying out ultrasonic treatment for 30 minutes, filtering, evaporating the filtrate to dryness, adding 10ml of water into residues to dissolve, adding 1ml of hydrochloric acid, heating and refluxing for 30 minutes, filtering, adding chloroform into the filtrate, shaking and extracting for 2 times, each time for 20ml, combining the chloroform solution, evaporating to dryness, and adding 1ml of chloroform into residues to dissolve to obtain a test sample solution; additionally, 1g of semen cassiae reference medicine is prepared into a reference medicine solution by the same method; adding methanol into the reference substance to obtain a solution containing 1mg per 1ml of the reference substance; absorbing 5u1 of each of the three solutions, respectively spotting on a silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with petroleum ether-ethyl formate-formic acid mixed at a volume ratio of 15:5:0.5 as a developing agent, taking out, airing, and placing an ultraviolet lamp for 365nm to be detected, wherein the same orange fluorescent spots appear in the chromatogram of the sample at the positions corresponding to the chromatograms of the reference medicinal materials and the reference substances;
2) Identification of glossy privet fruit
Taking 10 pieces of test sample, removing film coat, grinding, adding methanol 20ml, heating and refluxing for 30 min, filtering, evaporating filtrate to dryness, adding water 20ml to dissolve the residue, extracting with petroleum ether at 60-90deg.C for 2 times, 20ml each time, mixing extractive solutions, evaporating to dryness, and adding absolute ethanol 2ml to dissolve the residue to obtain test sample solution; preparing a reference medicinal material solution of glossy privet fruit by the same method by taking 1g of reference medicinal material of glossy privet fruit; taking oleanolic acid reference substance, adding absolute ethyl alcohol to prepare a solution containing 1mg per 1ml, taking the solution as a reference substance solution, sucking 5u1 of each of the three solutions, respectively spotting on a silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with cyclohexane-acetone-ethyl acetate-formic acid mixed in a volume ratio of 5:2:1:0.5 as a developing agent, taking out, airing, spraying 10% v/v sulfuric acid ethanol solution, heating at 110 ℃ until spots develop clearly, and developing spots with the same color on the positions corresponding to the chromatograms of the reference medicinal material and the reference substance in the chromatogram of the sample to be tested;
3) Identification of Lycium barbarum
Taking 10 pieces of test sample, removing coating, grinding, adding 50ml of water, heating and boiling for 15 minutes, cooling, filtering, shaking and extracting filtrate with ethyl acetate for 2 times, 20ml each time, mixing ethyl acetate solutions, and concentrating to 1ml to obtain test sample solution; preparing 1g of wolfberry fruit reference medicine, and preparing a reference medicine solution by the same method; absorbing 5u1 of each of the three solutions, respectively spotting on the same silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with chloroform-methanol-formic acid mixed with a volume ratio of 20:1:1 as a spreading agent, taking out, airing, and placing under a 365nm ultraviolet lamp for detection; in the chromatogram of the test sample, fluorescent spots with the same color appear at the positions corresponding to the chromatogram of the reference medicinal material;
(II) content detection
1) Detection of chrysophanol content
The chromatographic condition and system applicability test uses octadecylsilane chemically bonded silica as filler; taking a mixed methanol-0.1% phosphoric acid solution with the volume ratio of 82:18 as a mobile phase; the detection wavelength is 254nm; the theoretical plate number is not less than 3000 calculated according to the creosote peak;
preparation of a control solution: taking a proper amount of chrysophanol reference substance, precisely weighing, adding methanol to prepare a solution containing 16 mug per 1 ml;
preparation of test solution: taking 10 pieces of a test sample, grinding, precisely weighing 3g, placing into a bottle with a plug, adding 25ml of methanol, sealing, weighing, heating and refluxing for 1 hour, cooling, weighing again, supplementing the reduced weight with methanol, shaking uniformly, filtering, precisely measuring 10ml of a continuous filtrate, evaporating to dryness, adding 20ml of residue into water, 2ml of hydrochloric acid and 20ml of chloroform, heating and refluxing for 1 hour, cooling, separating to obtain chloroform liquid, shaking and extracting the water liquid with chloroform for 3 times, 15ml each time, merging the chloroform liquid, evaporating to dryness, adding a proper amount of methanol into the residue to dissolve, transferring to a 5ml measuring bottle, adding methanol until a scale person shakes with a star to obtain the product;
assay: respectively precisely sucking 10u1 of reference substance solution and 10u1 of sample solution, injecting into liquid chromatograph, and measuring to obtain the final product; each tablet of the sample contains 0.1mg of semen cassiae calculated by chrysophanol;
2) Lutein content detection
Chromatographic column: c18 column, 5 μm,250mm×4.6mm;
mobile phase: mobile phase A is a solution of 0.1% BHT in which methanol and water are mixed according to a volume ratio of 80:20, mobile phase B is methyl tertiary butyl ether containing 0.1% w/v BHT, and gradient elution is carried out according to the following steps;
flow rate: 1.0mL/min;
detection wavelength: 445nm;
column temperature: 20 ℃;
sample injection amount: 20 μl;
standard stock solution: accurately weighing 5mg of lutein, dissolving with ethanol solution containing 0.1% w/v BHT, and fixing volume to 100ml;
standard working solution: accurately transferring 0.050mL, 0.100mL, 0.200mL, 0.400mL and 1.00mL of solution from the lutein standard stock solution to 5 25mL brown volumetric flasks, and fixing the volume to scale by using an ethanol solution containing 0.1% w/v BHT to obtain a series of standard working solutions with the concentration of 0.100ug/mL, 0.200ug/mL, 0.400 ug/mL, 0.800ug/mL and 2.00 ug/mL;
test solution: accurately weighing 2g of uniform sample in a 50mL polypropylene centrifuge tube, adding about 0.2g of BHT and 10mL of ethanol, mixing uniformly, adding 10mL of 10% potassium hydroxide solution, stirring uniformly by vortex, oscillating and saponifying for 30min at room temperature in a dark place, oscillating and extracting for 3min by vortex at dark place with 10mL of extraction solvent, centrifuging for 3min at 4500r/min, repeating the extraction for 2 times, combining the extracts, washing with 10mL of water, layering by centrifuging for 3min at 4500r/min, repeating the washing for 1 time, concentrating the combined organic phase to near dryness at room temperature under reduced pressure, oscillating and dissolving residues by vortex with ethanol solution containing 0.1% of BHT, fixing the volume to 5mL, and filtering with a 0.45 mu m filter membrane;
And (3) respectively injecting the standard working solution into liquid chromatography to determine the corresponding peak areas, drawing a standard curve by taking the concentration of the standard working solution as an abscissa and the peak areas as an ordinate, and calculating the solution of the sample according to an external standard method.
Compared with the prior art, the invention has the beneficial effects that:
according to the invention, the content of lutein in the wolfberry fruit is improved through researching the primordium, pretreatment and percolation process of the wolfberry fruit medicinal material; the lutein is supplemented, so that senile macular degeneration (AMD) and the risk of cataract development can be reduced, meanwhile, the disease condition of cataract patients is obviously improved, the lutein is extremely unstable and is easy to decompose under the influence of light and temperature, most of traditional Chinese medicine compositions do not take the lutein as an effective component for investigation, in order to improve the treatment effect of the traditional Chinese medicine compositions, the process research is carried out on the lutein in the wolfberry fruit, the crushing degree of the wolfberry fruit is controlled to 75%, the percolation speed is controlled to 3.5ml/min/kg, the lutein content in the wolfberry fruit can be effectively improved, and the extraction rate is improved by 4.3 times.
By researching the basic source, pretreatment and extraction process of the cassia seed medicinal material, the content of the active ingredient chrysophanol in the cassia seed medicinal material is improved, and the content of polysaccharide in the cassia seed is also improved. The invention relates to a traditional Chinese medicine composition with eyesight improving effect, which only examines the content of chrysophanol and can not examine the polysaccharide of the cassia seed as the effective component, the invention takes the chrysophanol and the polysaccharide of the cassia seed as the effective component examination index, the invention adopts the examination of the producing area and picking time of the cassia seed medicinal material and adopts the mode of tearing the cassia seed medicinal material into two parts for pretreatment, and combines the mode of crushing and extracting the dregs, thus simultaneously improving the content of chrysophanol and polysaccharide in the cassia seed, wherein the content of chrysophanol is improved by 45.4%, and the content of polysaccharide of the cassia seed can be improved by 12.6%.
The invention deeply ploughs and finely works the medlar and cassia seed technology and preparation in the composition on the basis of the prior art means, obtains a preparation method and a quality control method of the composition with stable technology and good reproducibility in the aspects of the transfer rate, the extraction rate and the like of the effective components, evaluates the content of the xanthophyll and the polysaccharide effective components of the cassia seed simultaneously except for evaluating the content of the chrysophanol in the composition, improves the extraction rate and the transfer rate of the effective components by innovation of the preparation method of a plurality of components in the composition, obtains the effect of improving the clinical effective rate by 96.67 percent, improves the effective rate by 16 percent compared with the conventional preparation method, and ensures that the composition can achieve effective treatment effect on early-stage and middle-stage patients.
Drawings
FIG. 1 is a graph showing the detection of chrysophanol content in extracts of different processes of extraction of semen Cassiae (experiment 1) in Experimental example 2;
FIG. 2 is a graph showing the detection of chrysophanol content in various extracts (experiment 2) of semen Cassiae extraction process in experiment 2;
FIG. 3 is a graph showing the detection of chrysophanol content in various extracts (experiment 3) of semen Cassiae extraction process in experiment 2;
FIG. 4 is a graph showing the detection of chrysophanol content in various extracts (experiment 4) of semen Cassiae extraction process in experiment 2;
FIG. 5 is a pattern of semen Cassiae identification;
FIG. 6 is a diagram of the identification of glossy privet fruit;
fig. 7 shows a wolfberry identification map.
Detailed Description
The present invention will be further illustrated with reference to the following specific examples, but the present invention is not limited to the following examples. It will be understood by those skilled in the art that various changes and substitutions of details and forms of the technical solution of the present invention may be made without departing from the spirit and scope of the present invention, but these changes and substitutions fall within the scope of the present invention.
Example 1 preparation method and quality control method of Chinese medicinal composition for treating cataract due to deficiency of liver-yin and kidney-yin and stagnation of qi and blood
Weighing the following raw materials in parts by weight:
400 parts of medlar, 300 parts of glossy privet fruit, 200 parts of rehmannia, 220 parts of cassia seed, 200 parts of chrysanthemum and 100 parts of achyranthes root.
(II) extracting and concentrating
1) Extraction of wolfberry fruit
Crushing the wolfberry fruit clean medicinal material with the crushing rate of 75%, weighing wolfberry fruit according to the weight parts, placing the wolfberry fruit clean medicinal material into a clean container, adding ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank, adding a large-aperture screen mesh wrapped by 100-mesh silk cloth at the bottom of the percolation tank, surrounding the periphery by using absorbent cotton surrounding pads, adding ethanol with the weight of 1.5 times of 60% v/v, discharging air in the medicinal material, capping, and soaking for 24 hours; percolating at a speed of 3.5ml/min/kg per minute until 60% v/v ethanol is added and percolating is completed, collecting percolate, and performing light-shielding operation in the whole process of percolating;
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum until the vacuum degree rises to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35, collecting paste, and sealing for later use;
2) Rehmannia root and achyranthes root extraction
Weighing rehmannia root slices and achyranthes root sections according to the weight parts, putting the rehmannia root slices and achyranthes root sections into an extraction tank, adding 10 times of drinking water by weight for the first time, and starting steam heating. When the liquid medicine in the extraction tank boils, extracting for 2 hours, and filtering the liquid medicine by using 200-mesh filter cloth; adding 10 times of drinking water, extracting for 1.5 hr, filtering with 200 mesh filter cloth, and discarding residue;
mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator; starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of a first sight glass in a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator to concentrate the extract to a relative density of 1.28-1.30, and collecting the extract for later use, wherein the first-effect temperature is 75-85 ℃, and the second-effect temperature is 65-75 ℃;
3) Semen Cassiae extract
Weighing semen cassiae according to the parts by weight, tearing and crushing the clean semen cassiae by a pair of rollers to split the clean semen cassiae into two parts, putting the two parts into an extraction tank, adding 10 times of drinking water by weight for the first time, extracting for 2 hours, centrifugally filtering the liquid medicine by a flat filter, grinding and crushing the medicinal residues, putting the medicinal residues into the extraction tank again, adding 8 times of drinking water by weight for the second time, extracting for 1.5 hours, filtering the medicinal residues by a 200-mesh filter cloth, and discarding the medicinal residues;
mixing the above two filtrates, concentrating in a double-effect energy-saving evaporation concentrator, and starting a vacuum pump until the first-effect vacuum degree rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of a first sight glass in a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating the concentrated extract into clear paste with the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use;
4) Chrysanthemum extraction
And (3) weighing chrysanthemum according to the weight parts, putting the chrysanthemum into a traditional Chinese medicine extraction tank, and adding drinking water for extraction twice. Adding 10 times of drinking water by weight for the first time, starting steam heating, circulating for 5 minutes when the temperature of the liquid medicine in the extraction tank reaches 70-75 ℃, regulating steam pressure to keep the liquid medicine at 70-75 ℃, leaching for 1.5 hours, and filtering the liquid medicine by using 200-mesh filter cloth; adding 8 times of drinking water, leaching for 1 hr, filtering the medicinal liquid with 200 mesh filter cloth, and discarding residue; mixing the two filtrates, concentrating in a double-effect energy-saving evaporation concentrator, and starting a vacuum pump until the first-effect vacuum degree rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating to the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use;
(III) preparation
1) Crushing
Pulverizing fructus Ligustri Lucidi into fine powder with 100 mesh stainless steel screen in pulverizer;
2) Mixing, granulating, drying, and grading
Placing pregelatinized starch and fructus Ligustri Lucidi fine powder into a rapid stirring granulator, mixing at high speed for 5 min to make the mixture uniform, sieving with 60 mesh sieve, placing into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract uniformly, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after the spraying, drying to air inlet temperature less than 65deg.C, discharging, sieving with 20 mesh sieve, granulating, and collecting granule;
3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use;
4) Tabletting
Tabletting the mixed granules, wherein each tablet weighs 0.62g, and the difference of tablet weights is ensured to be within the range of 0.62g plus or minus 5.0%;
5) Coating and packaging
Coating the substrate according to standard, and packaging.
(IV) quality control
1. Authentication detection
1) Identification of semen Cassiae
Taking 10 pieces of a test sample, removing a film coating, grinding, adding 20ml of methanol, soaking for 1 hour, carrying out ultrasonic treatment for 30 minutes, filtering, evaporating the filtrate to dryness, adding 10ml of water into residues to dissolve, adding 1ml of hydrochloric acid, heating and refluxing for 30 minutes, filtering, adding chloroform into the filtrate, shaking and extracting for 2 times, each time for 20ml, combining the chloroform solution, evaporating to dryness, and adding 1ml of chloroform into residues to dissolve to obtain a test sample solution; additionally, 1g of semen cassiae reference medicine is prepared into a reference medicine solution by the same method; adding methanol into the reference substance to obtain a solution containing 1mg per 1ml of the reference substance; absorbing 5u1 of each of the three solutions, respectively spotting on a silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with petroleum ether-ethyl formate-formic acid mixed at a volume ratio of 15:5:0.5 as a developing agent, taking out, airing, and placing an ultraviolet lamp for 365nm to be detected, wherein the same orange fluorescent spots appear in the chromatogram of the sample at the positions corresponding to the chromatograms of the reference medicinal materials and the reference substances;
2) Identification of glossy privet fruit
Taking 10 pieces of test sample, removing film coat, grinding, adding methanol 20ml, heating and refluxing for 30 min, filtering, evaporating filtrate to dryness, adding water 20ml to dissolve the residue, extracting with petroleum ether at 60-90deg.C for 2 times, 20ml each time, mixing extractive solutions, evaporating to dryness, and adding absolute ethanol 2ml to dissolve the residue to obtain test sample solution; preparing a reference medicinal material solution of glossy privet fruit by the same method by taking 1g of reference medicinal material of glossy privet fruit; taking oleanolic acid reference substance, adding absolute ethyl alcohol to prepare a solution containing 1mg per 1ml, taking the solution as a reference substance solution, sucking 5u1 of each of the three solutions, respectively spotting on a silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with cyclohexane-acetone-ethyl acetate-formic acid mixed in a volume ratio of 5:2:1:0.5 as a developing agent, taking out, airing, spraying 10% sulfuric acid ethanol solution, heating at 110 ℃ until spots develop clearly, and developing spots with the same color on the positions corresponding to the chromatograms of the reference medicinal material and the reference substance in the chromatogram of the sample to be tested;
3) Identification of Lycium barbarum
Taking 10 pieces of test sample, removing coating, grinding, adding 50ml of water, heating and boiling for 15 minutes, cooling, filtering, shaking and extracting filtrate with ethyl acetate for 2 times, 20ml each time, mixing ethyl acetate solutions, and concentrating to 1ml to obtain test sample solution; preparing 1g of wolfberry fruit reference medicine, and preparing a reference medicine solution by the same method; absorbing 5u1 of each of the three solutions, respectively spotting on the same silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with chloroform-methanol-formic acid mixed with a volume ratio of 20:1:1 as a spreading agent, taking out, airing, and placing under a 365nm ultraviolet lamp for detection; in the chromatogram of the test sample, fluorescent spots with the same color appear at the positions corresponding to the chromatogram of the reference medicinal material;
2. content detection
1) Detection of chrysophanol content
The chromatographic condition and system applicability test uses octadecylsilane chemically bonded silica as filler; taking a mixed methanol-0.1% phosphoric acid solution with the volume ratio of 82:18 as a mobile phase; the detection wavelength was 254nm. The theoretical plate number is not less than 3000 calculated according to the creosote peak;
preparation of a control solution: taking a proper amount of chrysophanol reference substance, precisely weighing, adding methanol to prepare a solution containing 16 mug per 1 ml;
Preparation of test solution: taking 10 pieces of a test sample, grinding, precisely weighing 3g, placing into a bottle with a plug, adding 25ml of methanol, sealing, weighing, heating and refluxing for 1 hour, cooling, weighing again, supplementing the reduced weight with methanol, shaking uniformly, filtering, precisely measuring 10ml of a continuous filtrate, evaporating to dryness, adding 20ml of residue into water, 2ml of hydrochloric acid and 20ml of chloroform, heating and refluxing for 1 hour, cooling, separating to obtain chloroform liquid, shaking and extracting the water liquid with chloroform for 3 times, 15ml each time, merging the chloroform liquid, evaporating to dryness, adding a proper amount of methanol into the residue to dissolve, transferring to a 5ml measuring bottle, adding methanol until a scale person shakes with a star to obtain the product;
assay: precisely sucking 10u1 of each of the reference solution and the sample solution, and injecting into a liquid chromatograph for measurement. Each tablet of the sample contains 0.1mg of semen cassiae calculated by chrysophanol;
2) Lutein content detection
Chromatographic column: c18 column, 5 μm,250mm×4.6mm;
mobile phase: mobile phase A is a solution of 0.1% BHT in which methanol and water are mixed according to a volume ratio of 80:20, mobile phase B is methyl tertiary butyl ether containing 0.1% w/v BHT, and gradient elution is carried out according to the following steps;
flow rate: 1.0mL/min;
detection wavelength: 445nm;
Column temperature: 20 ℃;
sample injection amount: 20 μl;
standard stock solution: accurately weighing 5mg of lutein, dissolving with ethanol solution containing 0.1% w/v BHT, and fixing volume to 100ml;
standard working solution: accurately transferring 0.050mL, 0.100mL, 0.200mL, 0.400mL and 1.00mL of the solution from the lutein standard stock solution to 5 25mL brown volumetric flasks, and fixing the volume to scale by using an ethanol solution containing 0.1% w/vBHT to obtain a series of standard working solutions with the concentration of 0.100ug/mL, 0.200ug/mL, 0.400 ug/mL, 0.800ug/mL and 2.00 ug/mL;
test solution: accurately weighing 2g of uniform sample in a 50mL polypropylene centrifuge tube, adding about 0.2g of BHT and 10mL of ethanol, mixing uniformly, adding 10mL of 10% potassium hydroxide solution, stirring uniformly by vortex, oscillating and saponifying for 30min at room temperature in a dark place, oscillating and extracting for 3min by vortex at dark place with 10mL of extraction solvent, centrifuging for 3min at 4500r/min, repeating the extraction for 2 times, combining the extracts, washing with 10mL of water, layering by centrifuging for 3min at 4500r/min, repeating the washing for 1 time, concentrating the combined organic phase to near dryness at room temperature under reduced pressure, oscillating and dissolving residues by vortex with ethanol solution containing 0.1% of BHT, fixing the volume to 5mL, and filtering with a 0.45 mu m filter membrane;
and (3) respectively injecting the standard working solution into liquid chromatography to determine the corresponding peak areas, drawing a standard curve by taking the concentration of the standard working solution as an abscissa and the peak areas as an ordinate, and calculating the solution of the sample according to an external standard method.
Example 2 preparation method and quality control method of Chinese medicinal composition for treating cataract due to liver-kidney yin deficiency and qi and blood stasis
Weighing the following raw materials in parts by weight:
200 parts of medlar, 150 parts of glossy privet fruit, 100 parts of rehmannia, 100 parts of cassia seed, 100 parts of chrysanthemum and 50 parts of achyranthes root.
The rest of the procedure is the same as in example 1.
Experimental example 1 extraction of Lycium barbarum
The wolfberry fruit plays a role in the traditional Chinese medicine composition as a monarch drug, modern researches show that the wolfberry fruit contains a large amount of lutein, wolfberry polysaccharide, free amino acid, betaine, vitamins and other substances, wherein the lutein plays an important role, and is spread over the outer retina makeup layer, so that the lutein is important for the development of retina, and the researches show that the lutein can be supplemented to remarkably reduce the senile macular degeneration (AMD) and reduce the risk of cataract development, and meanwhile, the disease condition of cataract patients is obviously improved. The quality of the wolfberry fruit extract plays a vital role in the curative effect of the traditional Chinese medicine composition, and the content of lutein directly influences the curative effect of the product. The conventional traditional Chinese medicine composition only takes the content of the lycium barbarum polysaccharide and the betaine as the standard of quality control, the content of lutein in the extract is not examined, the stability of the lutein is very poor and is easily influenced by various factors, the lutein isomerization reaction can be caused in the heat treatment process so as to influence the content of the lutein, meanwhile, the problems of swelling, high viscosity and the like of the lycium barbarum medicinal material in the extraction process can occur, so that the active ingredients can not be sufficiently extracted, and the quality of the traditional Chinese medicine composition is further influenced.
In order to improve the lutein content in the wolfberry extract, the invention discovers that the crushing rate of wolfberry medicinal materials and the research of percolation equipment and technology find that the crushing rate of wolfberry medicinal materials is 75 percent, a conical percolation tank is adopted, the percolation speed is controlled at 3.5ml/min/kg per minute, and the lutein content in wolfberry can be furthest reserved by adopting a whole-process light-shielding operation mode, and the research is as follows:
1. treatment of wolfberry fruit and selection of percolating tank
Swelling of the wolfberry fruit medicinal material in the extraction process is common, the medicinal material has higher viscosity, if the crushing degree of the medicinal material is too large, the smaller the medicinal powder particles are, the higher the density below a percolation tank is easily caused in the percolation process, and the percolation effect is influenced by blockage; if the medicinal material is crushed Cheng Duguo, the larger the medicinal powder particles, the smaller the specific surface area of the particles, the contact between the medicinal powder and the solvent is affected, and the active ingredients of the medicinal material are difficult to dissolve out. Meanwhile, the shape of the percolator is generally cylindrical and conical, the shape of the percolator is selected relative to the expansibility of medicinal materials, the pressure center of the cylindrical percolator is arranged at the bottom of the tank, the conical part of the conical percolator can disperse partial pressure of the bottom of the tank, the cylindrical percolator and the conical part of the conical part are applicable to different medicinal materials, and the percolating effects are different. In order to improve the lutein content in the wolfberry fruits, the granularity of broken wolfberry fruits and the selection of a percolation tank directly influence the effect and quality of percolation. In order to fully extract the lutein content in the wolfberry fruits, the invention performs the following optimization comparison research on the wolfberry fruit treatment and percolation process.
Experiment 1: pulverizing fructus Lycii, adding 1 times of 60% v/v ethanol, stirring, covering, moistening for 4 hr, loading into cylindrical percolating tank (100 mesh gauze wrapped with absorbent cotton pad is arranged at the bottom of percolating tank), adding 1.5 times of 60% v/v ethanol, exhausting air, covering, and soaking for 24 hr. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.16 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 2: pulverizing fructus Lycii, adding 1 times of 60% v/v ethanol, stirring, covering, moistening for 4 hr, loading into conical percolating tank (100 mesh silk cloth wrapped large-aperture screen is added at bottom of percolating tank, absorbent cotton pad is used around), adding 1.5 times of 60% v/v ethanol, exhausting air, covering, and soaking for 24 hr. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 3: crushing the wolfberry fruit, weighing wolfberry fruit with a crushing rate of 75% according to the prescription, placing the wolfberry fruit into a clean container, adding ethanol with a weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a cylindrical percolating tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolating tank, absorbent cotton surrounding pads are adopted around), adding ethanol with a weight of 1.5 times of 60% v/v, discharging air in the medicinal material, capping, and soaking for 24 hours. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 4: crushing the wolfberry fruit, weighing wolfberry fruit with a crushing rate of 75% according to the prescription, placing the wolfberry fruit into a clean container, adding a proper amount of ethanol with a weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around), adding ethanol with a weight of 1.5 times of 60% v/v, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 5: crushing the wolfberry fruit, the crushing rate is 50%, weighing wolfberry fruit according to the prescription amount, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a cylindrical percolation tank (the bottom of the percolation tank is added with a large-aperture screen wrapped by 100-mesh silk cloth, absorbent cotton surrounding pads are adopted around), adding ethanol with the weight of 60% v/v which is 1.5 times that of the wolfberry fruit, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 6: crushing the wolfberry fruit, the crushing rate is 50%, weighing wolfberry fruit according to the prescription amount, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen mesh wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around), adding ethanol with the weight of 60% v/v which is 1.5 times that of the wolfberry fruit, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 7: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 25% according to the prescription, placing the wolfberry fruit into a clean container, adding ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a cylindrical percolating tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolating tank, absorbent cotton surrounding pads are adopted around), adding ethanol with the weight of 1.5 times of 60% v/v, discharging air in the medicinal material, capping, and soaking for 24 hours. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 8: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 50% in the amount of the prescription, adding ethanol in the amount of 60% v/v in 1 time, stirring, capping, moistening for 4 hr, packing into a cone-shaped percolating tank with 100 mesh gauze, packing with absorbent cotton, adding ethanol in the amount of 60% v/v in 1.5 time, exhausting air from the wolfberry fruit, capping, soaking for 24 hr. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 9: crushing the wolfberry fruit, weighing wolfberry fruit according to the prescription amount, placing the wolfberry fruit into a clean container, adding ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a cylindrical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted at the periphery), adding ethanol with the weight of 1.5 times of 60% v/v, exhausting air in the medicinal material, capping, and soaking for 24 hours. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 10: crushing the wolfberry fruit, weighing wolfberry fruit according to the prescription amount, placing the wolfberry fruit into a clean container, adding ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling into a conical percolation tank (a large-aperture screen mesh wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted at the periphery), adding ethanol with the weight of 1.5 times of 60% v/v, exhausting air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
In order to compare the differences of the extraction modes, the prepared wolfberry extract is subjected to lutein content detection, and the detection results are shown in the following table 1.
TABLE 1 detection results of lutein content in Lycium barbarum extract
Conclusion: from the above detection results, experiment 4 shows that the method comprises crushing fructus Lycii by 75%, selecting a conical percolating tank, adding a filtering device in the tank, and preventing lutein from degrading in fructus Lycii extract by isolating oxygen and avoiding light in the whole process, wherein the highest lutein content in fructus Lycii extract in the extraction method of experiment 4 is 12.8mg/100g. Compared with other test groups, the lutein extract has the advantages of retaining more lutein content and having the best extraction effect.
2. Percolation speed
The wolfberry fruit medicinal material contains a certain sugar, and the percolating effect is affected by the exuded viscous substances after crushing and solvent infiltration, and researches show that the percolating speed is too high, the extracting effect is insufficient, the concentration gradient in the fluid is reduced due to too low percolating speed, and the leaching of the active ingredients is not facilitated. According to the invention, through examining the percolating speed, a high gradient concentration difference is always formed between the solvent and the medicinal material particles in the percolating process, so that the lutein content in the wolfberry extract is improved, and the treatment effect of the Chinese medicinal composition is further improved.
Experiment 1: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 75% according to the prescription, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around the percolation tank), adding ethanol with the weight of 60% v/v of 1.5 times, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 1ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 2: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 75% according to the prescription, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around the percolation tank), adding ethanol with the weight of 60% v/v of 1.5 times, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 2ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 3: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 75% according to the prescription, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around the percolation tank), adding ethanol with the weight of 60% v/v of 1.5 times, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 2.5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 4: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 75% according to the prescription, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around the percolation tank), adding ethanol with the weight of 60% v/v of 1.5 times, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 3ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists at the temperature of an evaporation chamber of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (za 80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 5: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 75% according to the prescription, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around the percolation tank), adding ethanol with the weight of 60% v/v of 1.5 times, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 3.5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 6: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 75% according to the prescription, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around the percolation tank), adding ethanol with the weight of 60% v/v of 1.5 times, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 4ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 7: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 75% according to the prescription, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around the percolation tank), adding ethanol with the weight of 60% v/v of 1.5 times, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 4.5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
Experiment 8: crushing the wolfberry fruit, weighing wolfberry fruit in the crushing rate of 75% according to the prescription, placing the wolfberry fruit in a clean container, adding a proper amount of ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture into a conical percolation tank (a large-aperture screen wrapped by 100-mesh silk cloth is added at the bottom of the percolation tank, absorbent cotton surrounding pads are adopted around the percolation tank), adding ethanol with the weight of 60% v/v of 1.5 times, discharging air in the wolfberry fruit, capping, and soaking for 24 hours. Percolating was carried out at a rate of 5ml/min/kg per minute. And (5) adding 60% v/v ethanol until the percolation is completed, and collecting the percolate. And (3) carrying out light-shielding operation in the whole percolating process.
Placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum, when the vacuum degree is increased to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35 (80 ℃ for heat measurement), collecting paste, and sealing for later use.
To compare the differences of the above percolation rates, the prepared wolfberry extracts were subjected to lutein content detection as shown in table 2 below.
TABLE 2 detection results of lutein content in wolfberry extracts at different percolation rates
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Conclusion: as shown by the detection results, in experiment 5, the medlar is crushed by 75%, a conical percolation tank is selected, a filtering device is added in the tank, oxygen is isolated in the percolation process, the whole process is protected from light, the percolation speed is controlled at 3.5ml/min/kg, and the lutein content in the medlar extract is highest and can reach 14.3mg/100g. The method can extract lutein from fructus Lycii to the maximum extent, and increase extraction rate by 4.3 times.
Experimental example 2 extraction of semen Cassiae
Semen Cassiae is bitter and sweet in taste and cool in nature, enters liver meridian and large intestine meridian, and has the effects of clearing liver fire, dispelling wind-damp, tonifying kidney and improving eyesight. Semen Cassiae can excite LDH activity in ciliary muscle of eye, promote LDH to participate in anaerobic glycolysis of sugar, reduce crystalline lens glucose content, prevent cataract, and increase blood supply of retina and optic nerve, thereby improving eyesight. The main active ingredients of the semen cassiae are anthraquinone, naphthopyranone, polysaccharide, amino acid, inorganic elements and the like, wherein the representative ingredients of anthraquinone such as aurantiol, emodin, chrysophanol, physcion and rhein are characteristic ingredients of semen cassiae, and researches show that the higher the content of anthraquinone glycoside taking chrysophanol as a parent nucleus in the semen cassiae is, the stronger the liver protection effect is, and further the better effects of clearing liver and improving vision can be achieved. Meanwhile, researches show that the cassia seed polysaccharide has a protective effect on rat glaucoma retina cells, and the curative effect of the traditional Chinese medicine composition is directly determined by the content of chrysophanol and the content of the cassia seed polysaccharide.
In order to improve the content of the effective components of the semen cassiae, the screening of the fructus lycii medicinal materials, the processing mode of raw materials and the extraction process are researched, the semen cassiae is torn and crushed, and the flat plate filtration and the mode of crushing and re-extracting the dregs are adopted, so that the effective components in the semen cassiae can be extracted to the greatest extent, the content of chrysophanol can be improved, the content of polysaccharide of the semen cassiae can be improved, and the quality standard of the traditional Chinese medicine composition can be effectively controlled through investigation of two content indexes, thereby improving the treatment effect of the finished product. The study was as follows:
1. semen cassiae medicinal material selection
(1) Selection of origin
The content of chrysophanol in the cassia seed medicinal materials in different producing areas is greatly different, so that the main component chrysophanol of the cassia seed in the medicinal preparation can reach the effective content, and the producing areas of the cassia seed are screened. The detection results are shown in table 3 below.
TABLE 3 detection results of the content of active ingredients of Cassia Torae semen in different producing areas
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Conclusion: the content detection of chrysophanol and aurantium in 10 cassia seed medicinal materials in different producing areas is carried out by experiments, and the detection result shows that the content of chrysophanol in the cassia seed medicinal materials in the producing areas of Anhui is the highest, the content of chrysophanol is 0.24%, and the content of aurantium is 0.15%. In order to achieve the quality of the traditional Chinese medicine preparation, cassia seed medicinal materials in Anhui province are selected as raw materials.
(2) Selection of harvesting month
After the production place of the cassia seeds is screened, the cassia seed medicinal materials picked in the current year of the production place of the Anhui are selected for screening the harvesting month, and the specific picking time of the cassia seeds is determined again, so that a powerful advantage is provided for the treatment effect of the medicinal preparation. The detection results are shown in the following table 4.
TABLE 4 detection results of active ingredient content of semen Cassiae at different recovery months of Anhui producing area
Conclusion: in order to achieve high-content extraction of chrysophanol in the active ingredient of the traditional Chinese medicine preparation, the preferable Anhui province semen cassiae medicinal material is subjected to screening for picking time, and in 9-12 months of proper semen cassiae picking time, the detection result of the chrysophanol content is compared, so that the chrysophanol content in the semen cassiae picked in 11 months is the highest, and the chrysophanol content is 0.28%, so that the semen cassiae picked in 11 months in Anhui province as a production place is selected as a medicinal material raw material.
(3) Selection of storage year
Based on screening of the production place and the harvesting month of the cassia seeds, the content of the extracted chrysophanol is still low, and research personnel search for higher standard requirements of the pharmaceutical preparation, screen the storage year of the cassia seeds, and the detection results are shown in the following table 5.
TABLE 5 detection results of the content of active ingredients of Cassia Torae semen in different storage years
Conclusion: in order to further improve the content of the chrysophanol in the pharmaceutical preparation, the cassia seed medicinal materials in different years are further screened, and experimental results show that the content of the chrysophanol in the cassia seed with the storage year of 8 years is 0.32 percent, and compared with the cassia seed medicinal materials with the storage year of other years, the cassia seed with the storage year of 8 years, which is picked in 11 months and is used as a production place in Anhui province, is selected as a raw material, and an optimal raw material is provided for the pharmaceutical preparation so as to ensure the high concentration requirement of the chrysophanol content.
2. Semen cassiae medicinal material treatment
In the process of extracting the cassia seed by adding water, colloid is dissolved out and coated outside seeds, so that the extraction effect of the cassia seed is difficult to filter and influence, and in order to improve the content of active ingredients in the cassia seed, the following research is carried out on the treatment of the cassia seed:
experiment 1: weighing semen Cassiae according to prescription, pulverizing semen Cassiae, sieving with 24 mesh sieve, adding 10 times of drinking water, extracting for 2 hr, and filtering with 200 mesh filter cloth. Adding 8 times of drinking water, extracting for 1.5 hr, filtering with 200 mesh filter cloth, and discarding residue.
Mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator. Starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the vacuum degree of the second effect rises to-0.06 to-0.08 MPa, the feeding valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of the first sight glass in the first and second effect evaporation chambers, and the feeding valve is closed. And (3) opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating the concentrated extract into clear paste with the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use.
Experiment 2: weighing semen Cassiae according to prescription, tearing and crushing semen Cassiae clean medicinal material by a pair of rollers to split semen Cassiae medicinal material into two parts, putting into an extraction tank, adding 10 times of drinking water for the first time, extracting for 2 hours, and filtering the medicinal liquid with 200 mesh filter cloth. Adding 8 times of drinking water, extracting for 1.5 hr, filtering with 200 mesh filter cloth, and discarding residue.
Mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator. Starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the vacuum degree of the second effect rises to-0.06 to-0.08 MPa, the feeding valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of the first sight glass in the first and second effect evaporation chambers, and the feeding valve is closed. And (3) opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating the concentrated extract into clear paste with the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use.
Experiment 3: weighing semen Cassiae according to prescription, adding semen Cassiae clean medicinal material into extraction tank, adding 10 times of drinking water for the first time, extracting for 2 hr, and filtering the medicinal liquid with 200 mesh filter cloth. Adding 8 times of drinking water, extracting for 1.5 hr, filtering with 200 mesh filter cloth, and discarding residue.
Mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator. Starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the vacuum degree of the second effect rises to-0.06 to-0.08 MPa, the feeding valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of the first sight glass in the first and second effect evaporation chambers, and the feeding valve is closed. And (3) opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating the concentrated extract into clear paste with the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use.
And detecting the contents of chrysophanol and polysaccharide of cassia seed in the fluid extract obtained by the experiment, and simultaneously calculating the transfer rate of the chrysophanol content in the medicinal materials, wherein the experimental results are shown in the following table 6.
Table 6 results of detecting content of chrysophanol and polysaccharide in semen Cassiae fluid extract
Conclusion: from the above experiments, in experiment 2, the semen Cassiae was torn and broken by a pair of rollers to split the semen Cassiae into two parts, and the content of chrysophanol and polysaccharide in the semen Cassiae extract was the highest.
3. Semen Cassiae extract
After the cassia seed medicinal material is extracted by adding water, colloidal substances are dissolved out, the colloid is wrapped outside the seeds, the content of active ingredients of the extract is difficult to filter, the quality and the curative effect of a product are further influenced, and the loss of the active ingredients of the cassia seed is reduced to the greatest extent.
Experiment 1: weighing semen Cassiae according to prescription, tearing and crushing semen Cassiae clean medicinal material by a pair of rollers to split semen Cassiae medicinal material into two parts, putting into an extraction tank, adding 10 times of drinking water for the first time, extracting for 2 hours, and filtering the medicinal liquid with 200 mesh filter cloth. Adding 8 times of drinking water, extracting for 1.5 hr, filtering with 200 mesh filter cloth, and discarding residue.
Mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator. Starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the vacuum degree of the second effect rises to-0.06 to-0.08 MPa, the feeding valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of the first sight glass in the first and second effect evaporation chambers, and the feeding valve is closed. And (3) opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating the concentrated extract into clear paste with the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use.
Experiment 2: weighing semen Cassiae according to prescription, tearing and crushing semen Cassiae clean medicinal material by a pair of rollers to divide semen Cassiae medicinal material into two parts, putting into an extraction tank, adding 10 times of drinking water by weight for extraction for 2 hours for the first time, centrifuging and filtering medicinal liquid by a flat filter, putting medicinal residues into the extraction tank again, adding 8 times of drinking water by weight for the second time, extracting for 1.5 hours, filtering medicinal liquid by 200 meshes of filter cloth, and discarding medicinal residues.
Mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator. Starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the vacuum degree of the second effect rises to-0.06 to-0.08 MPa, the feeding valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of the first sight glass in the first and second effect evaporation chambers, and the feeding valve is closed. And (3) opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating the concentrated extract into clear paste with the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use.
Experiment 3: weighing semen Cassiae according to prescription, tearing and crushing semen Cassiae clean medicinal material by a pair roller machine to divide semen Cassiae medicinal material into two parts, adding into an extraction tank, adding 10 times of drinking water by weight for the first time, extracting for 2 hours, centrifuging and filtering medicinal liquid by a flat filter, grinding and crushing medicinal residues, adding into the extraction tank again, adding 8 times of drinking water by weight for the second time, extracting for 1.5 hours, filtering medicinal liquid by 200-mesh filter cloth, and discarding medicinal residues.
Mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator. Starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the vacuum degree of the second effect rises to-0.06 to-0.08 MPa, the feeding valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of the first sight glass in the first and second effect evaporation chambers, and the feeding valve is closed. And (3) opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating the concentrated extract into clear paste with the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use.
Experiment 4: weighing semen Cassiae according to prescription, tearing and crushing semen Cassiae clean medicinal material by a pair of rollers to split semen Cassiae medicinal material into two parts, adding into an extraction tank, adding 10 times of drinking water by weight for the first time, extracting for 2 hours, filtering the medicinal liquid with 200 mesh filter cloth, and flushing and filtering with 5 times of 90-100deg.C drinking water by weight during filtering. Adding 8 times of drinking water, extracting for 1.5 hr, filtering with 200 mesh filter cloth, and discarding residue.
Mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator. Starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the vacuum degree of the second effect rises to-0.06 to-0.08 MPa, the feeding valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of the first sight glass in the first and second effect evaporation chambers, and the feeding valve is closed. And (3) opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating the concentrated extract into clear paste with the relative density of 1.28-1.30 (60 ℃ for thermal measurement), and collecting the clear paste for later use.
And (3) detecting the content of chrysophanol in the fluid extract obtained by the experiment, and simultaneously calculating the transfer rate of the chrysophanol content in the medicinal material, wherein the experimental result is shown in the following table 7. The detection patterns are shown in figures 1-4.
TABLE 7 detection results of chrysophanol content in extracts of different extraction processes of semen Cassiae
Conclusion: as can be seen from the above experiments, in experiment 3, the semen Cassiae is torn and broken by a pair of rollers, so that the semen Cassiae medicinal material is torn into two parts, and the effective components in the semen Cassiae can be extracted to the maximum extent by combining the mode of grinding and breaking the residues after the first extraction and then extracting, thereby avoiding a great amount of loss caused by the filtering of the effective components in the thick medicinal liquid. Can increase the content of chrysophanol and polysaccharide in semen Cassiae, wherein the content of chrysophanol is increased by 45.4%, and the content of polysaccharide in semen Cassiae is increased by 12.6%, thereby improving the quality and therapeutic effect of the product.
Experimental example 3 selection of glossy privet fruit medicinal materials
Ligustrum lucidum ait is cool in nature, sweet and bitter in taste, enters liver and kidney meridians. Has effects of nourishing liver and kidney, nourishing liver, improving eyesight, invigorating kidney, nourishing blood, promoting blood circulation, protecting liver, and improving vision. The glossy privet fruits are planted in a wide distribution area in China, the ripening time of the fruits in each area is greatly different, and the content of active ingredients of the glossy privet fruits is also influenced by different harvesting periods and areas, so that the curative effect of a finished product is influenced. In order to improve the content of the effective components of the glossy privet fruit in the traditional Chinese medicine composition, the invention researches the producing area and the harvesting period of glossy privet fruit medicinal materials, and finally selects the glossy privet fruit which is harvested in the middle and earlier period of the Shandong producing area, wherein the content of oleanolic acid is the highest. The study procedure was as follows:
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Conclusion: in order to maximize the content of the effective components of the glossy privet fruit in the traditional Chinese medicine composition, preferably glossy privet fruit medicinal materials in the middle and earlier stages of Shandong province are picked, and the content of oleanolic acid is maximized and is 1.24%.
Experimental example 4 selection of auxiliary Material and amount
The common auxiliary material filler is sucrose, and cataract and glaucoma caused by kidney deficiency are frequently occurred in the old people, so that diabetics cannot take the pharmaceutical preparation, however, the ratio of patients suffering from diabetes in the patients is not small, and the patients cannot normally use the pharmaceutical preparation. Therefore, the invention performs the following study on the selection and the dosage of auxiliary materials.
1. Experiment 1
(1) Crushing
Pulverizing fructus Ligustri Lucidi and sucrose into fine powder with 100 mesh stainless steel screen respectively.
(2) Mixing, granulating, drying, and grading
Mixing sucrose and fructus Ligustri Lucidi fine powder in a rapid stirring granulator for 5 min at high speed to make it uniform, sieving with 60 mesh sieve, adding into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after spraying paste, drying to air inlet temperature less than 65deg.C, discharging, standing at room temperature, and sieving with 20 mesh sieve. The particles were collected.
(3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
2. Experiment 2
(1) Crushing
Pulverizing fructus Ligustri Lucidi into fine powder with 100 mesh stainless steel screen in pulverizer.
(2) Mixing, granulating, drying, and grading
Mixing dextrin and fructus Ligustri Lucidi fine powder in a rapid stirring granulator for 5 min at high speed to obtain uniform mixture, sieving with 60 mesh sieve, adding into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after spraying, drying to air inlet temperature less than 65deg.C, discharging, and standing at room temperature with 20 mesh sieve. The particles were collected.
(3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
3. Experiment 3
(1) Crushing
Pulverizing fructus Ligustri Lucidi into fine powder with 100 mesh stainless steel screen in pulverizer.
(2) Mixing, granulating, drying, and grading
Mixing pregelatinized starch and fructus Ligustri Lucidi fine powder in a rapid stirring granulator for 5 min at high speed to obtain uniform mixture, sieving with 60 mesh sieve, adding into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract, heating to 60-70deg.C, setting air inlet temperature of 75deg.C, spraying liquid, granulating, stopping heating after the spraying, drying to air inlet temperature of less than 65deg.C, discharging, standing to room temperature, and sieving with 20 mesh sieve to obtain granule. The particles were collected.
(3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
4. Experiment 4
(1) Crushing
Pulverizing fructus Ligustri Lucidi into fine powder with 100 mesh stainless steel screen in pulverizer.
(2) Mixing, granulating, drying, and grading
Placing microcrystalline cellulose and fructus Ligustri Lucidi fine powder into a rapid stirring granulator, mixing at high speed for 5 min to make it uniform, sieving with 60 mesh sieve, placing into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract uniformly, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after the spraying, drying to air inlet temperature less than 65deg.C, discharging, standing to room temperature, and sieving with 20 mesh sieve to obtain granule. The particles were collected.
(3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
5. Experiment 5
(1) Crushing
Pulverizing fructus Ligustri Lucidi into fine powder with 100 mesh stainless steel screen in pulverizer.
(2) Mixing, granulating, drying, and grading
Mixing corn starch and fructus Ligustri Lucidi fine powder in a rapid stirring granulator for 5 min at high speed to obtain uniform mixture, sieving with 60 mesh sieve, adding into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after spraying, drying to air inlet temperature less than 65deg.C, discharging, standing at room temperature, and sieving with 20 mesh sieve. The particles were collected.
(3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
The tablets prepared in the above experiments were tested for appearance, friability, weight difference, disintegration time, and the difference between tablets prepared with different excipients was compared, and the test results are shown in table 8 below.
Table 8 results of testing tablets prepared with different excipients
Conclusion: as shown by the experiment and the detection result, compared with the tablet with sucrose as the common auxiliary material, the auxiliary material in the experiment 3 is pregelatinized starch, and the prepared tablet is the most consistent with the original process. The appearance is complete and smooth, the color and luster are uniform, the friability weight loss is less than 1%, 20 tablets in weight difference meet the regulations, and the total disintegration is carried out when the disintegration time is 52 minutes. In order to solve the problem that the diabetics cannot take the tablets prepared by the original process, pregelatinized starch is selected as an auxiliary material to prepare the tablets, so that the types of unsuitable people are reduced, and good news is brought to the diabetics suffering from liver-kidney yin deficiency type cataract and glaucoma.
Experimental example 5 optimization of formulation Process
The glossy privet fruit medicinal material contains fatty oil substances up to 14.9%, so that tabletting is difficult and molding is difficult, and the appearance, friability, disintegration time and the like of the tablet are not in accordance with standard requirements, and the following study is carried out on the technical problem.
1. Experiment 1
(1) Crushing
Pulverizing fructus Ligustri Lucidi and pregelatinized starch into fine powder respectively with 100 mesh stainless steel screen in pulverizer.
(2) Mixing, granulating, drying, and grading
Mixing sucrose and fructus Ligustri Lucidi fine powder in a rapid stirring granulator for 5 min at high speed to make it uniform, sieving with 60 mesh sieve, adding into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after spraying paste, drying to air inlet temperature less than 65deg.C, discharging, standing at room temperature, and sieving with 20 mesh sieve. The particles were collected.
(3) General mixing
The granules are placed in a three-dimensional mixer after finishing, 0.1kg of magnesium stearate and 0.25kg of talcum powder are added and mixed for 15 minutes, and the dry granules are collected for standby.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
2. Experiment 2
(1) Crushing
Pulverizing fructus Ligustri Lucidi and sucrose into fine powder with 100 mesh stainless steel screen respectively.
(2) Mixing, granulating, drying, and grading
Mixing sucrose and fructus Ligustri Lucidi fine powder in a rapid stirring granulator for 5 min at high speed to make the mixture uniform, sieving with 60 mesh sieve, adding into a one-step granulator, adding 95% v/v ethanol by spraying, preheating at 75deg.C for 15 min, mixing radix rehmanniae and radix Achyranthis bidentatae fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract, heating to 60-70deg.C, spraying liquid at air inlet temperature of 75deg.C, granulating, stopping heating after spraying paste, drying to air inlet temperature of less than 65deg.C, discharging, and standing at room temperature with 20 mesh sieve. The particles were collected.
(3) General mixing
The granules are placed in a three-dimensional mixer after finishing, 0.1kg of magnesium stearate and 0.25kg of talcum powder are added and mixed for 15 minutes, and the dry granules are collected for standby.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
3. Experiment 3
(1) Crushing
Pulverizing fructus Ligustri Lucidi and sucrose into fine powder with 100 mesh stainless steel screen respectively.
(2) Mixing, granulating, drying, and grading
Placing sucrose and glossy privet fruit fine powder into a rapid stirring granulator for high-speed mixing for 5 minutes to make the sucrose and glossy privet fruit fine powder uniform, sieving the mixture with a 60-mesh sieve, putting the mixture into a one-step granulator, preheating the mixture for 15 minutes at 75 ℃, uniformly mixing the rehmannia root achyranthes root clear paste, the cassia seed clear paste, the chrysanthemum clear paste and the medlar clear paste according to the prescription, heating the mixture to 60-70 ℃, setting the air inlet temperature to 75 ℃, spraying liquid, granulating, stopping heating after the spraying paste, drying the mixture until the air inlet temperature is less than 65 ℃, discharging the mixture, putting the mixture to room temperature, adding 95% v/v ethanol in a spraying mode, wherein the adding amount is 2-3% of the total amount of the granules, mixing the mixture for 10 minutes, naturally airing the mixture for 10 minutes, repeating the steps of mixing and airing the mixture for 3 times, and finishing the granules with a 20-mesh sieve. The particles were collected.
(3) General mixing
The granules are placed in a three-dimensional mixer after finishing, 0.1kg of magnesium stearate and 0.25kg of talcum powder are added and mixed for 15 minutes, and the dry granules are collected for standby.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
4. Experiment 4
(1) Crushing
Pulverizing fructus Ligustri Lucidi and sucrose into fine powder with 100 mesh stainless steel screen respectively.
(2) Mixing, granulating, drying, and grading
Mixing sucrose and fructus Ligustri Lucidi fine powder in a rapid stirring granulator for 5 min at high speed to make it uniform, sieving with 60 mesh sieve, adding into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after spraying paste, drying to air inlet temperature less than 65deg.C, discharging, standing at room temperature, and sieving with 20 mesh sieve. The particles were collected.
(3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use.
(4) Tabletting
The mixed granules were tabletted, each tablet weighing 0.62g, ensuring a tablet weight difference within the range of 0.62 g.+ -. 5.0%.
(5) Coating and packaging
Coating the substrate according to standard, and packaging.
Tablets of different appearances were obtained according to the different preparation methods of the above experiment, the appearances thereof were recorded and the friability, weight difference, disintegration time were examined, and the examination results are shown in table 9 below.
Table 9 results of tablet testing for different modes of preparation
Conclusion: according to the results of the tablets prepared in the experiment, the experiment 4 adopts the steps that after total mixing, 95% v/v ethanol is added before tabletting, so that the prepared tablets have complete and smooth appearance, uniform color and luster, friability and weight loss less than 1%, 20 tablets in weight difference meet the regulations, and all the tablets disintegrate when the disintegration time is 50 minutes and meet the highest standard requirement of the tablets. Solves the problem of difficult tabletting and forming caused by high content of fatty oil substances in glossy privet fruits.
Experimental example 6 identification test
The Chinese medicinal composition is subjected to identification detection of semen cassiae, glossy privet fruit and medlar. The detection patterns are shown in figures 5-7. The identification experiment shows that the same fluorescent spots are displayed on the positions of the cassia seed, the glossy privet fruit and the medlar corresponding to the chromatogram of the reference medicinal materials and the chromatogram of the reference substance in the medicinal preparation, so that the effective components of the three medicinal materials in the medicinal preparation can be detected, and the quality detection of the effective substances of the product can be carried out.
Experimental example 7 comparative test of the preparation Process of the present invention and the original preparation Process
The results of the measurement of the active ingredients of the traditional Chinese medicine composition prepared by the invention and the traditional Chinese medicine composition produced by the original preparation process are shown in table 10.
Table 10 results of detection of the content of active ingredient in different preparation processes
Conclusion: according to the comparison test, the content of the active ingredient chrysophanol in the traditional Chinese medicine composition for treating cataract with the symptoms of liver-kidney yin deficiency and qi and blood stasis prepared by the invention can reach 0.1386 mg/tablet, which is improved by 38.6% compared with the standard, the content of the polysaccharide of the cassia seed is improved by 35.82%, the content of the lutein can be improved by 2.54 times, the product quality standard is greatly improved, and the treatment effect of the product can be further improved.
Clinical test example application of traditional Chinese medicine composition for treating cataract with symptoms of liver-kidney yin deficiency and qi and blood stasis
Clinical test example one clinical test for treating cataract caused by deficiency of liver-yin and kidney-yin
1. Case selection
60 cataract patients suffering from different degrees of liver-kidney yin deficiency were selected as the subjects of the study. They were divided into control and test groups using a randomized method, with 30 patients in each group. 14 men and 16 women in the control group, and the ages of 20-65 years old; the test group had 12 men and 18 women, ages 23 to 60 years. The general data of the two groups of patients are compared, the difference has no statistical significance (P is more than 0.05), and the two groups of patients are comparable.
Patient inclusion criteria:
(1) Meets the clinical diagnosis standard of cataract caused by liver-kidney yin deficiency;
(2) No pharmaceutical preparation was taken before the experiment;
(3) The patient himself voluntarily participates in the test and is highly matched;
2. therapeutic method
The control group was given 9 g/time of six ingredients with rehmannia pills 2 times daily;
test group the pharmaceutical preparation prepared in example 1 of the present invention was orally administered 3 tablets/time 3 times daily. Both groups were treated for 1 month with continued dosing.
3. Treatment efficacy assessment criteria
The effect is shown: the vision is recovered to be normal, the dizziness and tinnitus symptoms disappear, and the soreness and weakness of waist and knees disappear; the method is effective: the dim eyesight symptom is partially recovered, the dizziness and tinnitus symptoms are relieved, and the soreness and weakness of waist and knees are relieved; invalidation: the dim eyesight symptoms are not improved, dizziness and tinnitus symptoms still exist, and the soreness and weakness of waist and knees are not disappeared.
4. Results
The clinical test results show that: the number of effective treatment cases of the test group is 14, the number of effective treatment cases is 15, and the effective rate is 96.67%; the number of effective treatment cases of the control group is 12, the number of effective treatment cases is 10, and the effective rate is 73.33%; the treatment effective rate of the test group is higher than that of the control group 31.83%. The experimental results are shown in table 11.
Table 11 comparison of two sets of clinical trial data
Name of the name | Number of cases | Has obvious effect | Effective and effective | Invalidation of | Effective rate (%) |
Test group | 30 | 14 | 15 | 1 | 96.67 |
Control group | 30 | 12 | 10 | 8 | 73.33 |
Clinical trial example two clinical trials for treating glaucoma
1. Case selection
80 cataract patients suffering from different degrees of liver-kidney yin deficiency are selected as the study objects. They were divided into control and test groups using a randomized method, with 40 patients in each group. 23 men and 17 women in the control group, and the ages of 20-65 years old; 25 men and 15 women in the test group, ages 23-60 years. The general data of the two groups of patients are compared, the difference has no statistical significance (P is more than 0.05), and the two groups of patients are comparable.
Patient inclusion criteria:
(1) Meets clinical diagnosis standards of glaucoma caused by deficiency of liver-yin and kidney-yin;
(2) No pharmaceutical preparation was taken before the experiment;
(3) The patient himself voluntarily participates in the test and is highly matched;
2. therapeutic method
The control group was given 1 methazolamide tablet/time 2 times daily;
the test group took the present pharmaceutical formulation 3 tablets/time 3 times daily. Both groups were treated for 1 month with continued dosing.
3. Treatment efficacy assessment criteria
The effect is shown: normal visual field, normal vision, disappearance of symptoms of eye soreness and distension, and normal intraocular pressure;
the method is effective: partial recovery of visual field, partial recovery of vision, relief of symptoms of eye soreness and distension, slightly higher intraocular pressure;
Invalidation: the visual field is not recovered, the vision is not recovered, the symptoms of the acid swelling of eyes are not relieved, and the intraocular pressure is high.
4. Results
The clinical test results show that: the number of effective treatment cases of the test group is 25, the number of effective treatment cases is 12, and the effective rate is 92.5%; the number of effective treatment cases of the control group is 12, the number of effective treatment cases is 11, and the effective rate is 57.5%; the treatment effective rate of the test group is higher than that of the control group 60.87%. The experimental results are shown in table 12. The patients in the control group have side effects such as lip numbness, facial numbness, general discomfort, renal colic and the like during the test period, and the patients in the test group have no side effects.
Table 12 comparison of two sets of clinical trial data
Name of the name | Number of cases | Has obvious effect | Effective and effective | Invalidation of | Effective rate (%) |
Test group | 40 | 25 | 12 | 3 | 92.5 |
Control group | 40 | 12 | 11 | 17 | 57.5 |
Clinical test example III the Chinese medicinal composition of the invention and the clinical test of the Chinese medicinal composition prepared by the original preparation process
1. Case selection
60 cataract patients suffering from different degrees of liver-kidney yin deficiency were selected as the subjects of the study. They were divided into control and test groups using a randomized method, with 40 patients in each group. Control group, 16 men and 14 women, age 20-65 years; trial groups of 12 men and 18 women, ages 22-65 years old; the general data of the two groups of patients are compared, the difference has no statistical significance (P is more than 0.05), and the two groups of patients are comparable.
Patient inclusion criteria:
(1) Meets clinical diagnosis standards of glaucoma caused by deficiency of liver-yin and kidney-yin;
(2) No pharmaceutical preparation was taken before the experiment;
(3) The patient himself voluntarily participates in the test and is highly matched;
2. therapeutic method
Control group: the traditional Chinese medicine composition for treating cataract caused by yin deficiency of liver and kidney and qi and blood stasis in the original preparation process is orally taken 3 tablets/time and 3 times a day. Both groups were treated for 1 month with continued dosing.
Test group: the traditional Chinese medicine composition for treating cataract caused by deficiency of liver-yin and kidney-yin and stagnation of qi and blood stasis prepared in the embodiment 1 of the invention is orally taken 3 tablets/time and 3 times a day. Both groups were treated for 1 month with continued dosing.
3. Treatment efficacy assessment criteria
The effect is shown: normal visual field, normal vision, disappearance of symptoms of eye soreness and distension, and normal intraocular pressure;
the method is effective: partial recovery of visual field, partial recovery of vision, relief of symptoms of eye soreness and distension, slightly higher intraocular pressure;
invalidation: the visual field is not recovered, the vision is not recovered, the symptoms of the acid swelling of eyes are not relieved, and the intraocular pressure is high.
4. Results
The clinical test results show that: the number of effective treatment cases of the test group is 14, the number of effective treatment cases is 15, and the effective rate is 96.67%; the number of effective treatment cases of the control group is 15, the number of effective treatment cases is 10, and the effective rate is 83.33%; the treatment effective rate of the test group is 16% higher than that of the control group. The traditional Chinese medicine composition for treating cataract caused by yin deficiency of liver and kidney and qi and blood stasis prepared by the invention has a treatment effect superior to that of the traditional Chinese medicine composition prepared by the prior preparation process, and has positive and beneficial treatment effect on clinical treatment of patients. The experimental results are shown in table 13.
Table 13 comparison of two sets of clinical trial data
Name of the name | Number of cases | Has obvious effect | Effective and effective | Invalidation of | Effective rate (%) |
Test group | 30 | 14 | 15 | 1 | 96.67 |
Control group | 30 | 15 | 10 | 5 | 83.33 |
Claims (6)
1. The traditional Chinese medicine composition for treating cataract caused by liver-kidney yin deficiency and qi and blood stasis is characterized by being prepared from the following raw materials in parts by weight:
100-500 parts of medlar, 100-400 parts of glossy privet fruit, 50-300 parts of rehmannia, 50-220 parts of cassia seed, 50-250 parts of chrysanthemum and 30-150 parts of achyranthes root.
2. The traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:
400 parts of medlar, 300 parts of glossy privet fruit, 200 parts of rehmannia, 220 parts of cassia seed, 200 parts of chrysanthemum and 100 parts of achyranthes root.
3. The traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:
200 parts of medlar, 150 parts of glossy privet fruit, 100 parts of rehmannia, 100 parts of cassia seed, 100 parts of chrysanthemum and 50 parts of achyranthes root.
4. Use of the traditional Chinese medicine composition according to claims 1-3 in preparing a medicament for treating cataract caused by deficiency of liver-yin and kidney-yin and stagnation of qi and blood.
5. A method of preparing the traditional Chinese medicine composition of any one of claims 1-3, comprising the steps of:
extracting and concentrating
1) Extraction of wolfberry fruit
Crushing the wolfberry fruit clean medicinal material with the crushing rate of 75%, weighing wolfberry fruit according to the weight parts, placing the wolfberry fruit in a clean container, adding ethanol with the weight of 60% v/v, stirring uniformly, capping, moistening for 4 hours, filling the mixture in a conical percolation tank, adding a large-aperture screen mesh wrapped by 100-mesh silk cloth at the bottom of the percolation tank, surrounding with absorbent cotton, adding ethanol with the weight of 1.5 times of 60% v/v, exhausting air in the medicinal material, capping, and soaking for 24 hours; percolating at a speed of 3.5ml/min/kg per minute until 60% v/v ethanol is added and percolating is completed, collecting percolate, and performing light-shielding operation in the whole process of percolating;
placing the percolate into a multifunctional alcohol recovery concentrator, recovering and concentrating ethanol, starting vacuum until the vacuum degree rises to-0.03 to-0.05 MPa, starting a feed valve, conveying filtrate into the multifunctional alcohol recovery concentrator, starting a steam valve, recovering ethanol until no alcohol smell exists in an evaporation chamber at the temperature of 70-80 ℃, concentrating until the relative density is 1.14-1.35, collecting paste, and sealing for later use;
2) Rehmannia root and achyranthes root extraction
Weighing rehmannia root slices and achyranthes root sections according to the weight parts, putting the rehmannia root slices and achyranthes root sections into an extraction tank, adding 10 times of drinking water by weight for the first time, and starting steam heating. When the liquid medicine in the extraction tank boils, extracting for 2 hours, and filtering the liquid medicine by using 200-mesh filter cloth; adding 10 times of drinking water, extracting for 1.5 hr, filtering with 200 mesh filter cloth, and discarding residue;
mixing the above two filtrates, and concentrating in a double-effect energy-saving evaporation concentrator; starting a vacuum pump, and when the vacuum degree of the first effect rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of a first sight glass in a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator to concentrate the extract to a relative density of 1.28-1.30, and collecting the extract for later use, wherein the first-effect temperature is 75-85 ℃, and the second-effect temperature is 65-75 ℃;
3) Semen Cassiae extract
Weighing semen cassiae according to the parts by weight, tearing and crushing the clean semen cassiae by a pair of rollers to split the clean semen cassiae into two parts, putting the two parts into an extraction tank, adding 10 times of drinking water by weight for the first time, extracting for 2 hours, centrifugally filtering the liquid medicine by a flat filter, grinding and crushing the medicinal residues, putting the medicinal residues into the extraction tank again, adding 8 times of drinking water by weight for the second time, extracting for 1.5 hours, filtering the medicinal residues by a 200-mesh filter cloth, and discarding the medicinal residues;
Mixing the above two filtrates, concentrating in a double-effect energy-saving evaporation concentrator, and starting a vacuum pump until the first-effect vacuum degree rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to 1/2 of a first sight glass in a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, namely, placing the concentrated extract into a double-effect concentrator to concentrate the extract to a relative density of 1.28-1.30, and collecting the extract for later use, wherein the first-effect temperature is 75-85 ℃, and the second-effect temperature is 65-75 ℃;
4) Chrysanthemum extraction
And (3) weighing chrysanthemum according to the weight parts, putting the chrysanthemum into a traditional Chinese medicine extraction tank, and adding drinking water for extraction twice. Adding 10 times of drinking water by weight for the first time, starting steam heating, circulating for 5 minutes when the temperature of the liquid medicine in the extraction tank reaches 70-75 ℃, regulating steam pressure to keep the liquid medicine at 70-75 ℃, leaching for 1.5 hours, and filtering the liquid medicine by using 200-mesh filter cloth; adding 8 times of drinking water, leaching for 1 hr, filtering the medicinal liquid with 200 mesh filter cloth, and discarding residue; mixing the two filtrates, concentrating in a double-effect energy-saving evaporation concentrator, and starting a vacuum pump until the first-effect vacuum degree rises to-0.03 to-0.05 MPa; when the secondary vacuum degree rises to-0.06 to-0.08 MPa, a feed valve is opened, the liquid medicine to be concentrated is respectively conveyed to a first-effect evaporation chamber and a second-effect evaporation chamber, and the feed valve is closed; opening a steam valve, regulating the steam pressure to be not more than 0.09Mpa, concentrating, wherein the first-effect temperature is 75-85 ℃, the second-effect temperature is 65-75 ℃, concentrating to the relative density of 1.28-1.30, and collecting the clear paste for later use;
(II) formulations
1) Crushing
Pulverizing fructus Ligustri Lucidi into fine powder with 100 mesh stainless steel screen in pulverizer;
2) Mixing, granulating, drying, and grading
Placing pregelatinized starch and fructus Ligustri Lucidi fine powder into a rapid stirring granulator, mixing at high speed for 5 min to make the mixture uniform, sieving with 60 mesh sieve, placing into a one-step granulator, preheating at 75deg.C for 15 min, mixing radix rehmanniae and Achyranthis radix fluid extract, semen Cassiae fluid extract, flos Chrysanthemi fluid extract and fructus Lycii fluid extract uniformly, heating to 60-70deg.C, setting air inlet temperature at 75deg.C, spraying liquid, granulating, stopping heating after the spraying, drying to air inlet temperature less than 65deg.C, discharging, sieving with 20 mesh sieve, granulating, and collecting granule;
3) General mixing
Placing the granules after finishing the granules in a three-dimensional mixer, adding 0.1kg of magnesium stearate and 0.25kg of talcum powder, mixing for 15 minutes, adding 95% v/v ethanol in a spraying mode, mixing for 10 minutes, naturally airing for 10 minutes, repeating the steps of mixing and airing for 3 times, and collecting the dried granules for later use;
4) Tabletting
Tabletting the mixed granules, wherein each tablet weighs 0.62g, and the difference of tablet weights is ensured to be within the range of 0.62g plus or minus 5.0%;
5) Coating and packaging
Coating the substrate according to standard, and packaging.
6. The preparation method according to claim 5, further comprising a quality control method for the Chinese medicinal composition, comprising the steps of:
(one) authentication detection
1) Identification of semen Cassiae
Taking 10 pieces of a test sample, removing a film coating, grinding, adding 20ml of methanol, soaking for 1 hour, carrying out ultrasonic treatment for 30 minutes, filtering, evaporating the filtrate to dryness, adding 10ml of water into residues to dissolve, adding 1ml of hydrochloric acid, heating and refluxing for 30 minutes, filtering, adding chloroform into the filtrate, shaking and extracting for 2 times, each time for 20ml, combining the chloroform solution, evaporating to dryness, and adding 1ml of chloroform into residues to dissolve to obtain a test sample solution; additionally, 1g of semen cassiae reference medicine is prepared into a reference medicine solution by the same method; adding methanol into the reference substance to obtain a solution containing 1mg per 1ml of the reference substance; absorbing 5u1 of each of the three solutions, respectively spotting on a silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with petroleum ether-ethyl formate-formic acid mixed at a volume ratio of 15:5:0.5 as a developing agent, taking out, airing, and placing an ultraviolet lamp for 365nm to be detected, wherein the same orange fluorescent spots appear in the chromatogram of the sample at the positions corresponding to the chromatograms of the reference medicinal materials and the reference substances;
2) Identification of glossy privet fruit
Taking 10 pieces of test sample, removing film coat, grinding, adding methanol 20ml, heating and refluxing for 30 min, filtering, evaporating filtrate to dryness, adding water 20ml to dissolve the residue, extracting with petroleum ether at 60-90deg.C for 2 times, 20ml each time, mixing extractive solutions, evaporating to dryness, and adding absolute ethanol 2ml to dissolve the residue to obtain test sample solution; preparing a reference medicinal material solution of glossy privet fruit by the same method by taking 1g of reference medicinal material of glossy privet fruit; taking oleanolic acid reference substance, adding absolute ethyl alcohol to prepare a solution containing 1mg per 1ml, taking the solution as a reference substance solution, sucking 5u1 of each of the three solutions, respectively spotting on a silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with cyclohexane-acetone-ethyl acetate-formic acid mixed in a volume ratio of 5:2:1:0.5 as a developing agent, taking out, airing, spraying 10% sulfuric acid ethanol solution, heating at 110 ℃ until spots develop clearly, and developing spots with the same color on the positions corresponding to the chromatograms of the reference medicinal material and the reference substance in the chromatogram of the sample to be tested;
3) Identification of Lycium barbarum
Taking 10 pieces of test sample, removing coating, grinding, adding 50ml of water, heating and boiling for 15 minutes, cooling, filtering, shaking and extracting filtrate with ethyl acetate for 2 times, 20ml each time, mixing ethyl acetate solutions, and concentrating to 1ml to obtain test sample solution; preparing 1g of wolfberry fruit reference medicine, and preparing a reference medicine solution by the same method; absorbing 5u1 of each of the three solutions, respectively spotting on the same silica gel G thin layer plate with sodium carboxymethylcellulose as an adhesive, spreading with chloroform-methanol-formic acid mixed with a volume ratio of 20:1:1 as a spreading agent, taking out, airing, and placing under a 365nm ultraviolet lamp for detection; in the chromatogram of the test sample, fluorescent spots with the same color appear at the positions corresponding to the chromatogram of the reference medicinal material;
(II) content detection
1) Detection of chrysophanol content
The chromatographic condition and system applicability test uses octadecylsilane chemically bonded silica as filler; taking a mixed methanol-0.1% phosphoric acid solution with the volume ratio of 82:18 as a mobile phase; the detection wavelength was 254nm. The theoretical plate number is not less than 3000 calculated according to the creosote peak;
preparation of a control solution: taking a proper amount of chrysophanol reference substance, precisely weighing, adding methanol to prepare a solution containing 16 mug per 1 ml;
preparation of test solution: taking 10 pieces of a test sample, grinding, precisely weighing 3g, placing into a bottle with a plug, adding 25ml of methanol, sealing, weighing, heating and refluxing for 1 hour, cooling, weighing again, supplementing the reduced weight with methanol, shaking uniformly, filtering, precisely measuring 10ml of a continuous filtrate, evaporating to dryness, adding 20ml of residue into water, 2ml of hydrochloric acid and 20ml of chloroform, heating and refluxing for 1 hour, cooling, separating to obtain chloroform liquid, shaking and extracting the water liquid with chloroform for 3 times, 15ml each time, merging the chloroform liquid, evaporating to dryness, adding a proper amount of methanol into the residue to dissolve, transferring to a 5ml measuring bottle, adding methanol until a scale person shakes with a star to obtain the product;
assay: precisely sucking 10u1 of each of the reference solution and the sample solution, and injecting into a liquid chromatograph for measurement. Each tablet of the sample contains 0.1mg of semen cassiae calculated by chrysophanol;
2) Lutein content detection
Chromatographic column: c18 column, 5 μm,250mm×4.6mm;
mobile phase: mobile phase A is a solution of 0.1% BHT in which methanol and water are mixed according to a volume ratio of 80:20, mobile phase B is methyl tertiary butyl ether containing 0.1% w/v BHT, and gradient elution is carried out according to the following steps;
flow rate: 1.0mL/min;
detection wavelength: 445nm;
column temperature: 20 ℃;
sample injection amount: 20 μl;
standard stock solution: accurately weighing 5mg of lutein, dissolving with ethanol solution containing 0.1% w/v BHT, and fixing volume to 100ml;
standard working solution: accurately transferring 0.050mL, 0.100mL, 0.200mL, 0.400mL and 1.00mL of solution from the lutein standard stock solution to 5 25mL brown volumetric flasks, and fixing the volume to scale by using an ethanol solution containing 0.1% w/v BHT to obtain a series of standard working solutions with the concentration of 0.100ug/mL, 0.200ug/mL, 0.400 ug/mL, 0.800ug/mL and 2.00 ug/mL;
test solution: accurately weighing 2g of uniform sample in a 50mL polypropylene centrifuge tube, adding about 0.2g of BHT and 10mL of ethanol, mixing uniformly, adding 10mL of 10% potassium hydroxide solution, stirring uniformly by vortex, oscillating and saponifying for 30min at room temperature in a dark place, extracting for 3min by vortex with 10mL of extraction solvent in dark place, centrifuging for 3min at 4500r/min, repeating the extraction for 2 times, combining the extracting solutions, washing with 10mL of water, layering by centrifugation for 3min at 4500r/min, repeating the washing for 1 time, concentrating the combined organic phase to near dryness at room temperature under reduced pressure, oscillating and dissolving residues by vortex with ethanol solution containing 0.1% w/v of BHT, fixing the volume to 5mL, and filtering with a 0.45 mu m filter membrane;
And (3) respectively injecting the standard working solution into liquid chromatography to determine the corresponding peak areas, drawing a standard curve by taking the concentration of the standard working solution as an abscissa and the peak areas as an ordinate, and calculating the solution of the sample according to an external standard method.
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1456296A (en) * | 2003-04-10 | 2003-11-19 | 毛友昌 | Tablets for improving vision acuity and nourishing kidney and preparation thereof |
CN1548090A (en) * | 2003-05-24 | 2004-11-24 | 毛友昌 | Eyesight improving and kidney-nourishing bolus and its prepn |
CN101897829A (en) * | 2009-05-27 | 2010-12-01 | 北京因科瑞斯医药科技有限公司 | Medicinal composition with function of alleviating visual fatigue and preparation method thereof |
CN104491181A (en) * | 2015-01-05 | 2015-04-08 | 哈尔滨乐泰药业有限公司 | Traditional Chinese medicine composition for treating alopecia as well as preparation method and application of traditional Chinese medicine composition |
CN112076151A (en) * | 2020-08-28 | 2020-12-15 | 乐泰药业有限公司 | A Chinese medicinal oral liquid for treating diabetes due to deficiency of both qi and yin, and its preparation method and quality control method |
CN115414441A (en) * | 2022-08-19 | 2022-12-02 | 乐泰药业有限公司 | Traditional Chinese medicine composition with effects of nourishing blood, regulating menstruation, removing blood stasis and removing ecchymoses as well as preparation method and application thereof |
-
2023
- 2023-08-31 CN CN202311120278.8A patent/CN116920027A/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1456296A (en) * | 2003-04-10 | 2003-11-19 | 毛友昌 | Tablets for improving vision acuity and nourishing kidney and preparation thereof |
CN1548090A (en) * | 2003-05-24 | 2004-11-24 | 毛友昌 | Eyesight improving and kidney-nourishing bolus and its prepn |
CN101897829A (en) * | 2009-05-27 | 2010-12-01 | 北京因科瑞斯医药科技有限公司 | Medicinal composition with function of alleviating visual fatigue and preparation method thereof |
CN104491181A (en) * | 2015-01-05 | 2015-04-08 | 哈尔滨乐泰药业有限公司 | Traditional Chinese medicine composition for treating alopecia as well as preparation method and application of traditional Chinese medicine composition |
CN112076151A (en) * | 2020-08-28 | 2020-12-15 | 乐泰药业有限公司 | A Chinese medicinal oral liquid for treating diabetes due to deficiency of both qi and yin, and its preparation method and quality control method |
CN115414441A (en) * | 2022-08-19 | 2022-12-02 | 乐泰药业有限公司 | Traditional Chinese medicine composition with effects of nourishing blood, regulating menstruation, removing blood stasis and removing ecchymoses as well as preparation method and application thereof |
Non-Patent Citations (5)
Title |
---|
任安: "眼科中成药知多少", 开卷有益(求医问药), no. 07, 2 July 2012 (2012-07-02), pages 40 - 41 * |
关亚会,等: "五味子木脂素类药理作用的研究", 黑龙江中医药, no. 06, 10 December 2008 (2008-12-10), pages 44 * |
刘畅,等: "山楂的药用价值研究", 黑龙江科技信息, no. 33, 25 November 2009 (2009-11-25), pages 245 * |
彭成,等主编: "《中国临床药物大辞典 中药成方制剂卷(上卷)》", vol. 01, 31 August 2018, 中国医药科技出版社, pages: 3029 * |
涂艳虹,等: "中西医结合治疗老年高血压病的临床观察", 湖北中医杂志, vol. 32, no. 05, 10 May 2010 (2010-05-10), pages 38 - 39 * |
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