Medicine for treating coronary heart disease and preparation method thereof

Abstract

The invention relates to a medicine for treating coronary heart disease and a preparation method thereof, and belongs to the field of medicines. The medicine is prepared from the following medicinal materials: American ginseng, pseudo-ginseng, schisandra chinensis, endothelium corneum gigeriae galli, dendrobe, cordyceps sinensis, hippocampus, cornu cervi pantotrichum, lucid ganoderma, snake gall, salvia miltiorrhiza, stigma croci, tortoise shell and turtle shell. The treatment mode of the tortoise shells and the turtle shells comprises the steps of extracting active ingredients in the tortoise shells and the turtle shells, continuously decocting and extracting the extracted tortoise shells and the turtle shells with new water, performing ultrafiltration and concentration to obtain tortoise shell clear paste, and taking the tortoise shell clear paste as a coating adhesive of the medicine. The medicine provided by the invention is stable in content, short in dissolution time limit and good in stability, avoids the use of refined honey, is favorable for diabetics to use, and has unexpected technical effects.

Description

Technical Field

[0001] The invention belongs to the field of medicines, and specifically relates to a medicine for treating coronary heart disease and a preparation method thereof. Background Art

[0002] Yi'anning Pills (CN100339111C Chinese medicine approved by China's State Food and Drug Administration and marketed under the name of "Yianning Pills") "has the effects of replenishing qi and activating blood circulation, benefiting the liver and strengthening the kidneys, nourishing the heart and calming the mind, improving intelligence and strengthening the brain. It can treat coronary heart disease and the chest tightness, shortness of breath, chills, cold limbs, numbness of hands and feet caused by it. It also has a certain effect on insomnia, forgetfulness, fatigue, soreness of waist and knees caused by aging."

[0003] The 2020 China Cardiovascular Health and Disease Report pointed out that the prevalence of atherosclerotic cardiovascular disease is gradually increasing, and the prevalence of coronary heart disease (CHD) is about 10.2‰. The latest report shows that the mortality rate of cardiovascular disease (CVD) ranks first in my country, among which the mortality rate of coronary heart disease is on the rise. In my country, coronary heart disease is the most common type of cardiovascular disease and has attracted attention worldwide. Coronary heart disease and diabetes are two chronic diseases that seriously endanger human health, but there is a close connection between the two. Nearly 35% of patients with coronary heart disease have diabetes, 14.6% of diabetic patients have coronary heart disease, and nearly 75% of diabetic patients die from cardiovascular disease.

[0004] At present, the latest diabetes guidelines in my country point out that the number of diabetes patients in my country is on the rise, and the current adult prevalence rate is 11.2%, of which type 2 diabetes is the main cause. Diabetes is considered to be "a disease of equal risk to CHD (coronary heart disease)" and "cancer of blood vessels." That is to say, for patients with diabetes, especially type 2 diabetes (T2DM), as time goes by, the risk of future macrovascular complications (cardiovascular disease events are mainly coronary heart disease) is close to that of non-diabetic patients who have been diagnosed with coronary heart disease and will have new cardiovascular events in the next 10 years. Cardiovascular disease, as the main complication of diabetic patients, is the primary factor causing death in diabetic patients, accounting for more than 70% of the total number of diabetic patients.

[0005] Yianning Pills are effective in treating coronary heart disease. However, the use of honey as an auxiliary ingredient in the preparation of the adhesive for pill making and coating adds a lot of extra sugar to the pills. As nearly half of today's coronary heart disease patients also have diabetes, it is difficult to meet the medication needs of patients with underlying hyperglycemia. Summary of the invention

[0006] In order to solve the above technical problems, the present invention provides the following technical solutions.

[0007] In a first aspect, the present invention provides a drug.

[0008] A medicine prepared from medicinal materials including American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, Dendrobium officinale, Cordyceps sinensis, Hippocampus, Pilose antler, Ganoderma lucidum, Snake gall, Salvia miltiorrhiza, Saffron, Tortoise shell and Turtle shell;

[0009] The method for processing the tortoise shell and turtle shell includes extracting the active ingredients from the tortoise shell and turtle shell, and using new water to continue decocting and extracting the extracted tortoise shell and turtle shell, ultrafiltering, and concentrating to obtain a tortoise and turtle shell paste, and using the tortoise and turtle shell paste as the coating adhesive of the drug.

[0010] In some embodiments, the tortoise shell and turtle shell processing method comprises:

[0011] (1) Cleaning tortoise and turtle shells;

[0012] (2) decoction extraction: decoct the cleaned tortoise shell and turtle shell in step (1), filter and microfilter to obtain an extract;

[0013] (3) Ultrafiltration: Ultrafiltration the extract obtained in step (2) to obtain a filtrate and an interception liquid; the filtrate obtained is the ultrafiltration filtrate of the turtle shell extract;

[0014] (4) Concentration: Concentrate the intercepted liquid obtained in step (3) to obtain the turtle and tortoise shell clear paste.

[0015] In some embodiments, the tortoise shell and turtle shell processing method comprises:

[0016] (1) Cleaning tortoise and turtle shells: steaming tortoise and turtle shells, removing rotten flesh from the tortoise and turtle shells, washing with water, and breaking into pieces to obtain cleaned tortoise and turtle shells;

[0017] (2) decoction extraction: the tortoise shell and turtle shell cleaned in step (1) are decocted and extracted 1 to 5 times (e.g., 1, 2, 3, 4 or 5 times) to obtain a water extract; each decoction extraction is performed for 12 to 48 hours (e.g., 12 hours, 15 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 25 hours, 40 hours, 45 hours or 48 hours), The ratio of the total mass of the tortoise shell and the turtle shell to the mass of water is 1:5-1:15 (such as 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14 or 1:15) in each decoction; the water extracts are combined, filtered to discard the filter residue, centrifuged to obtain the supernatant, and microfiltered to obtain an extract; the pore size of the filter membrane of the microfiltration in step (2) is 1 μm-5 μm (such as 1 μm, 2 μm, 3 μm, 4 μm or 5 μm);

[0018] (3) Ultrafiltration: Ultrafiltration the extract obtained in step (2) to obtain a filtrate and an interception liquid; the filtrate obtained is the ultrafiltration filtrate of the turtle shell extract; the ultrafiltration molecular weight cutoff is 50 kDa-100 kDa, preferably 50 kDa-60 kDa;

[0019] (4) Concentration: The intercepted liquid obtained in step (3) is subjected to membrane concentration and low-temperature vacuum concentration to a solid content of 40 wt%-50 wt% to obtain a turtle and tortoise shell clearing paste.

[0020] In some embodiments, the molecular weight cutoff of the ultrafiltration in step (3) is 50 kDa-100 kDa. In some embodiments, the molecular weight cutoff of the ultrafiltration in step (3) is 50 kDa, 60 kDa, 70 kDa, 80 kDa, 90 kDa or 100 kDa. In some preferred embodiments, the molecular weight cutoff of the ultrafiltration in step (3) is 50 kDa-60 kDa.

[0021] In some embodiments, the pore size of the filter membrane of the microfiltration in step (2) is 0.1 μm-10 μm. In some embodiments, the pore size of the filter membrane of the microfiltration in step (2) is 0.1 μm, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm or 10 μm. In some preferred embodiments, the pore size of the filter membrane of the microfiltration in step (2) is 1 μm-5 μm. In some more preferred embodiments, the pore size of the filter membrane of the microfiltration in step (2) is 2 μm.

[0022] In some embodiments, the pore size of the filter mesh used for filtering in step (2) is 50 μm-150 μm. In some embodiments, the pore size of the filter mesh used for filtering in step (2) is 50 μm, 60 μm, 70 μm, 74 μm, 75 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm or 150 μm. In some embodiments, the pore size of the filter mesh used for filtering in step (2) is 74 μm.

[0023] In some embodiments, the concentration in step (4) is carried out by membrane concentration and vacuum concentration.

[0024] In some embodiments, the membrane concentration in step (4) is performed by nanofiltration membrane or reverse osmosis membrane concentration.

[0025] In some embodiments, the pore size of the nanofiltration membrane in step (4) is 1 nm-2 nm.

[0026] In some embodiments, the pore size of the reverse osmosis membrane in step (4) is 0.1 nm-1.0 nm. In some embodiments, the pore size of the reverse osmosis membrane in step (4) is 0.1 nm, 0.2 nm, 0.3 nm, 0.4 nm, 0.5 nm, 0.6 nm, 0.7 nm, 0.8 nm, 0.9 nm or 1.0 nm.

[0027] In some embodiments, the concentration of step (4) is concentrated to a solid content of 40wt%-50wt%. In some embodiments, the concentration of step (4) is concentrated to a solid content of 40wt%, 41wt%, 42wt%, 43wt%, 44wt%, 45wt%, 46wt%, 47wt%, 48wt%, 49wt% or 50wt%.

[0028] In some embodiments, the step (2) comprises: boiling and extracting the tortoise shell and turtle shell cleaned in step (1) for 1 to 5 times (e.g., 1, 2, 3, 4 or 5 times) to obtain a water extract; each boiling and extraction is for 12 to 48 hours (e.g., 12 hours, 15 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 25 hours, 40 hours, 45 hours or 48 hours), and the ratio of the total mass of the tortoise shell and turtle shell to the mass of water is 1:5-1:10 (e.g., 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14 or 1:15); combining the water extracts, filtering and discarding the filter residue, centrifuging to obtain the supernatant, and microfiltering to obtain an extract.

[0029] In some embodiments, step (1) comprises: steaming tortoise shells and turtle shells, removing rotten flesh from the tortoise shells and turtle shells, washing with water, breaking into pieces, and obtaining cleaned tortoise shells and turtle shells.

[0030] In some embodiments, the tortoise shell and turtle shell processing method comprises:

[0031] (i) cleaning tortoise and turtle shells;

[0032] (ii) decoction extraction: decoct the cleaned tortoise shell and turtle shell obtained in step (i) together with some other medicinal materials, filter and concentrate to obtain a clear paste C;

[0033] (iii) continuing to decoct: replacing the tortoise shell and turtle shell decocted in step (ii) with new water and continuing to decoct, filtering, and microfiltering to obtain an extract;

[0034] (iv) ultrafiltration: ultrafiltration the extract obtained in step (iii) to obtain a filtrate and an interception liquid;

[0035] (v) Concentration: The intercepted liquid obtained in step (iv) is concentrated to obtain the turtle and tortoise shell clearing paste.

[0036] In some embodiments, the tortoise shell and turtle shell processing method comprises:

[0037] (i) cleaning tortoise shells and turtle shells: steaming the tortoise shells and turtle shells, removing the rotten flesh from the tortoise shells and turtle shells, washing with water, and breaking into pieces to obtain cleaned tortoise shells and turtle shells;

[0038] (ii) decoction extraction: decoct the tortoise shell and turtle shell cleaned in step (i) together with some other medicinal materials, filter and concentrate to obtain a clear paste C;

[0039] (iii) continuing to decoct: adding water to the tortoise shell and the turtle shell decocted in step (ii) and decocting and extracting for 1 to 5 times (e.g., 1, 2, 3, 4 or 5 times) to obtain a water extract; each decoction and extraction is for 12 to 48 hours (e.g., 12 hours, 15 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 25 hours, 40 hours, 45 hours or 48 hours) , the ratio of the total mass of the tortoise shell and the turtle shell to the mass of water each time the decoction is 1:5-1:15 (such as: 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14 or 1:15); the water extracts are combined, filtered to discard the filter residue, centrifuged to obtain the supernatant, and microfiltered to obtain an extract; the pore size of the filter membrane of the microfiltration in the step (iii) is 1μm-5μm (such as: 1μm, 2μm, 3μm, 4μm or 5μm);

[0040] (iv) ultrafiltration: ultrafiltration the extract obtained in step (iii) to obtain a filtrate and an interception liquid; the ultrafiltration molecular weight cut-off is 50 kDa-100 kDa, preferably 50 kDa-60 kDa;

[0041] (v) Concentration: The intercepted liquid obtained in step (iv) is subjected to membrane concentration and low-temperature vacuum concentration to a solid content of 40 wt%-50 wt% to obtain a turtle and tortoise shell clearing paste.

[0042] In some embodiments, the molecular weight cutoff of the ultrafiltration in step (iv) is 50 kDa-100 kDa. In some embodiments, the molecular weight cutoff of the ultrafiltration in step (iv) is 50 kDa, 60 kDa, 70 kDa, 80 kDa, 90 kDa or 100 kDa. In some preferred embodiments, the molecular weight cutoff of the ultrafiltration in step (iv) is 50 kDa-60 kDa.

[0043] In some embodiments, the pore size of the filter membrane of the microfiltration in step (iii) is 0.1 μm-10 μm. In some embodiments, the pore size of the filter membrane of the microfiltration in step (iii) is 0.1 μm, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm or 10 μm. In some preferred embodiments, the pore size of the filter membrane of the microfiltration in step (iii) is 1 μm-5 μm. In some more preferred embodiments, the pore size of the filter membrane of the microfiltration in step (iii) is 2 μm.

[0044] In some embodiments, the pore size of the filter mesh used for filtering in step (iii) is 50 μm-150 μm or 74 μm. In some embodiments, the pore size of the filter mesh used for filtering in step (iii) is 50 μm, 60 μm, 70 μm, 74 μm, 75 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm or 150 μm. In some embodiments, the pore size of the filter mesh used for filtering in step (iii) is 74 μm.

[0045] In some embodiments, the concentration in step (v) is performed by membrane concentration and vacuum concentration.

[0046] In some embodiments, the membrane concentration in step (v) is performed by nanofiltration membrane or reverse osmosis membrane concentration.

[0047] In some embodiments, the pore size of the nanofiltration membrane in step (v) is 1 nm-2 nm.

[0048] In some embodiments, the pore size of the reverse osmosis membrane in step (v) is 0.1 nm-1.0 nm. In some embodiments, the pore size of the reverse osmosis membrane in step (v) is 0.1 nm, 0.2 nm, 0.3 nm, 0.4 nm, 0.5 nm, 0.6 nm, 0.7 nm, 0.8 nm, 0.9 nm or 1.0 nm.

[0049] In some embodiments, the concentration of step (v) is concentrated to a solid content of 40wt%-50wt%. In some embodiments, the concentration of step (v) is concentrated to a solid content of 40wt%, 41wt%, 42wt%, 43wt%, 44wt%, 45wt%, 46wt%, 47wt%, 48wt%, 49wt% or 50wt%.

[0050] In some embodiments, step (iii) comprises: decoct and extract the tortoise shell and turtle shell obtained after decoction in step (ii) for 1 to 5 times (e.g., 1 time, 2 times, 3 times, 4 times or 5 times) to obtain a water extract; decoct and extract for 12 hours to 48 hours each time (e.g., 12 hours, 15 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 31 hours, 32 hours, 33 hours, 34 hours, 35 hours, 36 hours, 37 hours, 38 hours, 39 hours, 40 hours, 41 hours, 42 hours, 43 hours, 44 hours, 45 hours, 46 hours, 47 hours, 48 ​​hours, 49 hours, 50 hours, 51 hours, 52 hours, 53 hours, 54 hours, 55 hours, 56 hours, 57 hours, 58 hours, 59 hours, 60 hours, 61 hours, 62 hours, 63 hours, 64 hours, 65 hours, 66 hours, 67 hours, 68 hours, 69 hours, 70 hours, 71 hours, 72 hours, 73 hours, 74 hours, 75 hours, 76 hours, 77 hours, 78 hours, 79 hours, 80 hours, 81 hours, 82 hours, 83 hours, 84 hours, 85 hours, 86 hours, 87 hours, 88 hours, 89 hours, 90 hours, 91 hours, 92 hours, 93 hours, 94 hours, 95 hours, 96 hours, 97 hours, 98 hours, 99 hours, 9 hours, 30 hours, 25 hours, 40 hours, 45 hours or 48 hours), the ratio of the total mass of the tortoise shell and the turtle shell to the mass of water each time is 1:5-1:15 (such as: 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14 or 1:15); combining the water extracts, filtering and discarding the filter residue, centrifuging to obtain the supernatant, microfiltering to obtain an extract; and / or

[0051] In some embodiments, step (i) comprises: steaming tortoise shells and turtle shells, removing rotten flesh from the tortoise shells and turtle shells, washing with water, breaking into pieces, and obtaining cleaned tortoise shells and turtle shells.

[0052] In some embodiments, part of the other medicinal materials in step (ii) is the entire prescription amount of deer antler, the entire prescription amount of Ganoderma lucidum, the entire prescription amount of snake gall, and one quarter to three quarters of the prescription amount (for example, one quarter of the prescription amount, two quarters of the prescription amount, or three quarters of the prescription amount) of Dendrobium, one quarter to three quarters of the prescription amount (for example, one quarter of the prescription amount, two quarters of the prescription amount, or three quarters of the prescription amount) of Cordyceps sinensis, one quarter to three quarters of the prescription amount (for example, one quarter of the prescription amount, two quarters of the prescription amount, or three quarters of the prescription amount) of Saffron, and one quarter to three quarters of the prescription amount (for example, one quarter of the prescription amount, two quarters of the prescription amount, or three quarters of the prescription amount) of Seahorse.

[0053] In some embodiments, in the preparation method of the drug, the salvia miltiorrhiza is added in the form of salvia miltiorrhiza powder, and the preparation method of the salvia miltiorrhiza powder comprises crushing the salvia miltiorrhiza at a temperature below -10°C and in a closed condition.

[0054] In some embodiments, the pulverizing step in the method for preparing salvia miltiorrhiza powder includes pulverizing under a nitrogen or inert gas atmosphere.

[0055] In some embodiments, in the preparation method of the drug, part of the prescribed amount of saffron is added in the form of saffron powder, and the remaining prescribed amount is added in the form of a decoction obtained by decocting and extracting saffron.

[0056] In some embodiments, the method for preparing saffron powder comprises crushing saffron at a temperature below -10°C in a sealed condition.

[0057] In some embodiments, the pulverizing step in the method for preparing saffron pollen includes pulverizing under a nitrogen or inert gas atmosphere.

[0058] In some embodiments, the drug is prepared from the following medicinal materials in parts by weight: American ginseng 26.4-75.9, Panax notoginseng 16.5-62.7, Schisandra 1.65-16.5, Chicken gizzard 1.65-16.5, Dendrobium 13.2-56.1, Cordyceps 3.3-29.7, Hippocampus 3.3-29.7, Deer antler 1.65-16.5, Ganoderma lucidum 3.3-29.7, Snake gall 1.65-16.5, Salvia miltiorrhiza 1.65-26.4, Crocus 3.3-29.7, Tortoise shell 26.4-75.9 and Turtle shell 16.5-62.7.

[0059] In some embodiments, the drug further comprises a coating powder.

[0060] In some embodiments, the coating powder includes at least one of red iron oxide mixed powder, talcum powder, and mixed powder of talcum powder and pigment.

[0061] In some embodiments, the weight portion of the coating powder is 3 parts to 9 parts. In some embodiments, the weight portion of the coating powder is 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts or 9 parts.

[0062] In some embodiments, the drug is in the form of a pill.

[0063] In a second aspect, the present invention provides a method for preparing the drug described in the first aspect.

[0064] A method for preparing the drug according to the first aspect, the method for preparing the drug comprising:

[0065] Step S1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, a portion of the prescribed amount of Dendrobium officinale, a portion of the prescribed amount of Cordyceps sinensis, and a portion of the prescribed amount of Hippocampus into fine powder, and mix them with Salvia miltiorrhiza powder and a portion of the prescribed amount of saffron powder to obtain a mixture A; the preparation method of the Salvia miltiorrhiza powder includes direct pulverization or preparation according to the preparation method of the Salvia miltiorrhiza powder in the medicine of the first aspect; the preparation method of the saffron powder includes direct pulverization or preparation according to the preparation method of the saffron powder in the medicine of the first aspect;

[0066] Step S2: Deer antler, ganoderma lucidum, snake gallbladder and the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron and the remaining prescription amount of seahorse as the medicinal materials to be decocted, add water and decoct for 1 to 5 times (such as 1 time, 2 times, 3 times, 4 times or 5 times) to obtain a decoction, combine the decoctions, filter to obtain a filtrate, mix the obtained filtrate with the ultrafiltration filtrate of the tortoise shell extract in step (2) of the medicine of the first aspect, and concentrate to obtain a clear paste B;

[0067] Step S3:

[0068] Step S3-1: Mix the mixture A obtained in step S1 and the clear paste B obtained in step S2, dry, crush, add water to make pills, dry, coat with coating powder and use the turtle and tortoise shell clear paste in step (4) of the drug of the first aspect as a coating adhesive, and polish to obtain the drug;

[0069] or

[0070] Step S3-2: Mix the mixture A obtained in step S1 and the clear paste B obtained in step S2, make pills, dry, coat with coating powder and use the turtle and tortoise shell clear paste described in step (4) of the drug described in the first aspect as a coating adhesive, and polish to obtain the drug.

[0071] In some embodiments, a method for preparing the drug of the first aspect comprises:

[0072] (A) Preparation of the ultrafiltration filtrate of turtle shell extract and turtle shell clear paste: performing operations according to steps (1) to (4) in the drug of the first aspect to obtain the ultrafiltration filtrate of turtle shell extract and turtle shell clear paste;

[0073] (B) Preparation of Danshen powder and saffron powder: preparing Danshen powder according to the preparation method of Danshen powder in the medicine of the first aspect or directly crushing Danshen to obtain Danshen powder; directly crushing three quarters of the prescription amount of saffron powder to obtain saffron powder or preparing saffron powder according to the preparation method of saffron powder in the medicine of the first aspect;

[0074] (C) Preparation of pills:

[0075] Step S1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, a portion of the prescribed amount of Dendrobium officinale, a portion of the prescribed amount of Cordyceps sinensis, and a portion of the prescribed amount of Hippocampus into fine powder, and mix the powder with the Salvia miltiorrhiza powder prepared in step (B) and three-quarters of the prescribed amount of saffron powder prepared in step (B) to obtain a mixture A;

[0076] Step S2: Deer antler, ganoderma lucidum, snake gallbladder and the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron and the remaining prescription amount of seahorse as the medicinal materials to be decocted, add water and decoct for 1 to 5 times (such as 1 time, 2 times, 3 times, 4 times or 5 times) to obtain a decoction, combine the decoctions, filter to obtain a filtrate, mix the obtained filtrate with the ultrafiltration filtrate of the tortoise shell extract in step (2) of the medicine of the first aspect, and concentrate to obtain a clear paste B;

[0077] Step S3:

[0078] Step S3-1: Mix the mixture A obtained in step S1 and the clear paste B obtained in step S2, dry, crush, add water to make pills, dry, coat with coating powder and use the turtle and tortoise shell clear paste in step (4) of the drug of the first aspect as a coating adhesive, and polish to obtain the drug;

[0079] or

[0080] Step S3-2: Mix the mixture A obtained in step S1 and the clear paste B obtained in step S2, make pills, dry, coat with coating powder and use the turtle shell clear paste described in step (4) of the drug described in the first aspect as a coating adhesive with coating powder, polish, and obtain the drug.

[0081] In some embodiments, the partial prescription amount of Dendrobium in step S1 is one quarter to three quarters of the prescription amount of Dendrobium. In some embodiments, the partial prescription amount of Dendrobium in step S1 is one quarter, two quarters or three quarters of the prescription amount of Dendrobium.

[0082] In some embodiments, the partial prescription amount of saffron in step S1 is one quarter to three quarters of the prescription amount of saffron. In some embodiments, the partial prescription amount of saffron in step S1 is one quarter, two quarters or three quarters of the prescription amount of saffron.

[0083] In some embodiments, the partial prescription amount of the hippocampus in step S1 is one quarter to three quarters of the prescription amount of the hippocampus. In some embodiments, the partial prescription amount of the hippocampus in step S1 is one quarter, two quarters or three quarters of the prescription amount of the hippocampus.

[0084] In some embodiments, the weight of water added each time water is added for decoction in step S2 is 5-15 times the total weight of the medicinal materials to be decocted. In some embodiments, the weight of water added each time water is added for decoction in step S2 is 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 11 times, 12 times, 13 times, 14 times or 15 times the total weight of the medicinal materials to be decocted.

[0085] In some embodiments, the boiling time of each time of adding water to boil in step S2 is 1 hour to 5 hours. In some embodiments, the boiling time of each time of adding water to boil in step S2 is 1 hour, 2 hours, 3 hours, 4 hours or 5 hours.

[0086] In some embodiments, the concentration in step S2 is to concentrate to a clear paste B with a relative density of 1.20-1.22 at 70°C.

[0087] In a third aspect, the present invention provides another method for preparing the drug described in the first aspect.

[0088] A method for preparing the drug according to the first aspect, the method for preparing the drug comprising:

[0089] Step P1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, a portion of the prescribed amount of Dendrobium officinale, a portion of the prescribed amount of Cordyceps sinensis and a portion of the prescribed amount of Hippocampus into fine powder, and mix them with Salvia miltiorrhiza powder and a portion of the prescribed amount of saffron powder to obtain a mixture A; the preparation method of the Salvia miltiorrhiza powder includes direct pulverization or preparation according to the preparation method of the Salvia miltiorrhiza powder in the medicine of the first aspect; the preparation method of the saffron powder includes direct pulverization or preparation according to the preparation method of the saffron powder in the medicine of the first aspect;

[0090] Step P2: using velvet antler, ganoderma lucidum, snake gallbladder, the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron, the remaining prescription amount of seahorse, and the cleaned tortoise shell and turtle shell obtained in step (i) of the drug of the first aspect as the medicinal materials to be decocted, adding water and decocting for 1 to 5 times (such as 1 time, 2 times, 3 times, 4 times or 5 times) to obtain a decoction, combining the decoctions, filtering to obtain a filtrate, mixing the obtained filtrate with the tortoise shell extract ultrafiltration filtrate, concentrating to obtain a clear paste C;

[0091] Step P3: preparing a tortoise and turtle shell paste by performing the decocted tortoise shell and turtle shell in step P2 according to steps (iii) to (v) of the medicine of the first aspect;

[0092] Step P4:

[0093] Step P4-1: Mix the mixture A obtained in step P1 and the clear paste C obtained in step P2, dry, crush, add water to make pills, dry, coat with coating powder and use the turtle and tortoise shell clear paste obtained in step P3 as a coating adhesive, and polish to obtain the drug;

[0094] or

[0095] Step P4-2: Mix the mixture A obtained in step P1 and the clear paste C obtained in step P2, make pills, dry, coat with coating powder and use the turtle shell clear paste obtained in step P3 as a coating adhesive, and polish to obtain the drug.

[0096] A method for preparing the drug according to the first aspect, the method for preparing the drug comprising:

[0097] Step P1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, a portion of the prescribed amount of Dendrobium officinale, a portion of the prescribed amount of Cordyceps sinensis, and a portion of the prescribed amount of Hippocampus into fine powder, and mix them with Salvia miltiorrhiza powder and three-quarters of the prescribed amount of saffron powder to obtain a mixture A; the preparation method of the Salvia miltiorrhiza powder includes direct pulverization or preparation according to the preparation method of the Salvia miltiorrhiza powder in the medicine of the first aspect; the preparation method of the saffron powder includes direct pulverization or preparation according to the preparation method of the saffron powder in the medicine of the first aspect;

[0098] Step P2:

[0099] Step P2-1: steaming tortoise shells and turtle shells, removing rotten flesh from the tortoise shells and turtle shells, washing with water, breaking into pieces, and obtaining cleaned tortoise shells and turtle shells;

[0100] Step P2-2: Deer antler, ganoderma lucidum, snake gallbladder, the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron, the remaining prescription amount of seahorse, and the cleaned tortoise shell and turtle shell obtained in step P2-1 are used as medicinal materials to be decocted, and water is added and decocted for 1 to 5 times (such as 1 time, 2 times, 3 times, 4 times or 5 times) to obtain a decoction, the decoctions are combined, filtered to obtain a filtrate, the obtained filtrate is mixed with the tortoise shell extract ultrafiltration filtrate, and concentrated to obtain a clear paste C;

[0101] Step P3: preparing a tortoise and turtle shell paste by performing the decocted tortoise shell and turtle shell in step P2 according to steps (iii) to (v) of the medicine of the first aspect;

[0102] Step P4:

[0103] Step P4-1: Mix the mixture A obtained in step P1 and the clear paste C obtained in step P2, dry, crush, add water to make pills, dry, coat with coating powder and use the turtle and tortoise shell clear paste obtained in step P3 as a coating adhesive, and polish to obtain the drug;

[0104] or

[0105] Step P4-2: Mix the mixture A obtained in step P1 with the clear paste C obtained in step P2, make pills, dry, coat with coating powder and use the turtle shell clear paste obtained in step P3 as a coating adhesive with coating powder, polish, and obtain the drug.

[0106] In some embodiments, the partial prescription amount of Dendrobium in step P1 is one quarter to three quarters of the prescription amount of Dendrobium. In some embodiments, the partial prescription amount of Dendrobium in step P1 is one quarter, two quarters or three quarters of the prescription amount of Dendrobium.

[0107] In some embodiments, the partial prescription amount of saffron in step P1 is one quarter to three quarters of the prescription amount of saffron. In some embodiments, the partial prescription amount of saffron in step P1 is one quarter, two quarters or three quarters of the prescription amount of saffron.

[0108] In some embodiments, the partial prescription amount of the hippocampus in step P1 is one quarter to three quarters of the prescription amount of the hippocampus. In some embodiments, the partial prescription amount of the hippocampus in step P1 is one quarter, two quarters or three quarters of the prescription amount of the hippocampus.

[0109] In some embodiments, the weight of water added each time water is added for decoction in step P2 is 5-15 times the total weight of the medicinal materials to be decocted. In some embodiments, the weight of water added each time water is added for decoction in step P2 is 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 11 times, 12 times, 13 times, 14 times or 15 times the total weight of the medicinal materials to be decocted.

[0110] In some embodiments, the boiling time of each time of adding water to boil in step P2 is 1 hour to 5 hours. In some embodiments, the boiling time of each time of adding water to boil in step P2 is 1 hour, 2 hours, 3 hours, 4 hours or 5 hours.

[0111] In some embodiments, the concentration in step P2 is to concentrate to a clear paste C with a relative density of 1.20-1.22 at 70°C.

[0112] In a fourth aspect, the present invention provides uses of the aforementioned drug or the drug prepared by the aforementioned preparation method.

[0113] Use of the drug of the first aspect or the drug prepared by the preparation method of the second aspect or the third aspect in preparing medicines for treating and / or coronary heart disease.

[0114] Beneficial Effects

[0115] Compared with the prior art, a certain embodiment of the present invention has at least one of the following beneficial effects:

[0116] (1) The present invention separates the adhesive component from the extract of turtle shell as an adhesive for pill making and / or coating, replacing the refined honey used in the prior art preparation method, avoiding the introduction of sugar, and improving the prior art preparation method.

[0117] (2) Compared with the preparation of pills using the tortoise shell extract ultrafiltration filtrate and tortoise shell paste obtained by ultrafiltration using other molecular weight cutoffs, the preparation of pills using the tortoise shell extract ultrafiltration filtrate and tortoise shell paste obtained by ultrafiltration using a molecular weight cutoff of 50kDa-100kDa (preferably 50kDa-60kDa) is more conducive to reducing the dissolution time of the obtained pills.

[0118] (3) The pellets prepared by the method provided by the present invention have good content stability.

[0119] (4) Compared with other coating adhesives, the use of the turtle shell glue provided by the present invention as a coating adhesive is more conducive to improving the stability of the ginsenoside content of the obtained pills.

[0120] (5) The present invention adopts low-temperature closed pulverization of Salvia miltiorrhiza and saffron, which is more conducive to improving the retention of active ingredients in Salvia miltiorrhiza and saffron, and increasing the content of active ingredients in Salvia miltiorrhiza and saffron in pills, which has unexpected technical effects.

[0121] (6) Compared with other coating adhesives, the coating adhesive provided by the present invention is more conducive to improving the stability of the crocin and salvianolic acid B content of the obtained pills, and has unexpected technical effects.

[0122] (7) Compared with other coating adhesives, the coating adhesive provided by the present invention is more conducive to improving the dissolution stability of the obtained pills, avoiding changes in the dissolution rate and dissolution curve of the obtained pills during transportation or storage, thereby affecting the bioavailability and product quality, and has unexpected technical effects.

[0123] (8) The use of the coating adhesive provided by the present invention and the addition of the ultrafiltration filtrate of the tortoise shell extract to the clear paste B or the clear paste C are more conducive to improving the dissolution stability of the obtained pills, avoiding changes in the solubility and dissolution curve of the obtained pills during transportation or storage, thereby affecting the bioavailability and product quality, and having unexpected technical effects.

[0124] (9) Compared with the preparation of pills by using turtle and tortoise shell paste obtained by ultrafiltration with a molecular weight cutoff of 50 kDa to 60 kDa, the present invention preferably uses turtle and tortoise shell paste obtained by ultrafiltration with a molecular weight cutoff of 50 kDa to prepare pills, which is more conducive to improving the dissolution stability of the obtained pills, avoiding changes in the solubility and dissolution curve of the obtained pills during transportation or storage, thereby affecting the bioavailability and product quality, and has unexpected technical effects.

[0125] Terminology

[0126] In the present invention, "room temperature" refers to ambient temperature, which may be 10°C-40°C, or 20°C-30°C; in some embodiments, it is 22°C-28°C; in some embodiments, it is 24°C-26°C; in some embodiments, it is 25°C.

[0127] In the above text of the present invention, regardless of whether the words "about" or "approximately" are used, all the numbers disclosed herein are approximate values. Based on the disclosed numbers, the value of each number may vary by less than ±10% or reasonable differences considered by those skilled in the art, such as ±1%, ±2%, ±3%, ±4% or ±5%.

[0128] The terms "optional", "optional" or "optionally" mean that the subsequently described event or circumstance may but need not occur.

[0129] The term "red iron oxide mixed powder" means that red iron oxide and talcum powder are mixed in a weight ratio of 1:20.

[0130] The term "parts by weight" refers to the mass fraction obtained by comparing the mass of a component of a composition with the mass of other components.

[0131] The term "filtrate" refers to the liquid that passes through the ultrafiltration membrane during ultrafiltration.

[0132] The term "rejection fluid" refers to the fluid that does not pass through the ultrafiltration membrane after ultrafiltration.

[0133] The term "and / or" should be understood to mean any one of the optional items or a combination of any two or more of the optional items.

[0134] The term "V / V" means volume ratio.

[0135] The term "wt%" means percent by mass.

[0136] The term "solid content" refers to the mass percentage of the solids obtained after the solvent is dried from the mixed liquid to the mixed liquid before drying.

[0137] The term "relative density" is the density compared to water at 25°C.

[0138] As used herein, the term "treatment" refers to clinical intervention intended to alter the natural course of a disease in the individual being treated. Desired therapeutic effects include, but are not limited to, preventing the onset or recurrence of a disease, alleviating symptoms, reducing any direct or indirect pathological consequences of a disease, preventing metastasis, reducing the rate of disease progression, improving or alleviating the disease state, and alleviating or improving prognosis.

[0139] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0140] In this application, "composition" can be conveniently presented in unit dosage form and can be prepared by any of the methods well known in the pharmaceutical art. All methods include the step of combining the active ingredient with a carrier that constitutes one or more accessory ingredients. Usually, the composition is prepared by uniformly and thoroughly combining the active compound with a liquid carrier, a finely divided solid carrier, or both.

[0141] In addition, it should be noted that, unless explicitly stated otherwise, the description methods used throughout this article, "each... and... are independently", "... and... are each independently", and "... and... are respectively independently" are interchangeable and should be understood in a broad sense, which can mean that in different groups, the specific options expressed by the same symbols do not affect each other, or that in the same group, the specific options expressed by the same symbols do not affect each other. BRIEF DESCRIPTION OF THE DRAWINGS

[0142] Figure 1 The dissolution curves of the pills obtained in Example 10 at 0 day and after being placed under accelerated conditions (40°C ± 2°C, 75% RH ± 5%) for 6 months are shown in Figure 10. The horizontal axis is time (minutes) and the vertical axis is the cumulative dissolution amount (%).

[0143] Figure 2 The dissolution curves of the pills obtained in Example 11 at 0 day and after being placed under accelerated conditions (40°C ± 2°C, 75% RH ± 5%) for 6 months are shown in Figure 11. The horizontal axis is time (minutes) and the vertical axis is the cumulative dissolution amount (%). Figure 3 The dissolution curves of the pills obtained in Comparative Example 2 at 0 day and after being placed under accelerated conditions (40°C ± 2°C, 75% RH ± 5%) for 6 months are shown in Figure 2. The horizontal axis is time (minutes) and the vertical axis is the cumulative dissolution amount (%).

[0144] Figure 4The dissolution curves of the pills obtained in Comparative Example 7 at 0 day and after being placed under accelerated conditions (40°C ± 2°C, 75% RH ± 5%) for 6 months are shown in Figure 1. The horizontal axis is time (minutes) and the vertical axis is the cumulative dissolution amount (%).

[0145] Figure 5 The dissolution curves of the pills obtained in Comparative Example 8 at 0 day and after being placed under accelerated conditions (40°C ± 2°C, 75% RH ± 5%) for 6 months are shown in Figure 1. The horizontal axis is time (minutes) and the vertical axis is the cumulative dissolution amount (%).

[0146] Figure 6 The dissolution curves of the pills obtained in Comparative Example 9 at 0 day and after being placed under accelerated conditions (40°C ± 2°C, 75% RH ± 5%) for 6 months are shown in Figure 1. The horizontal axis is time (minutes) and the vertical axis is the cumulative dissolution amount (%). DETAILED DESCRIPTION

[0147] In order to enable those skilled in the art to better understand the technical solution of the present invention, some non-limiting embodiments are further disclosed below to further illustrate the present invention in detail.

[0148] The reagents used in the present invention can be purchased from the market or prepared by the method described in the present invention or by conventional methods in the art.

[0149] Unless otherwise specified, the detection methods in the embodiments, comparative examples and test examples of the present invention adopt the following methods:

[0150] 1. Detection method of L-hydroxyproline, glycine, alanine and L-proline content:

[0151] Chromatographic conditions: ZORBAX Eclipse Plus C18 chromatographic column (250mm×4.6mm, 5μm); acetonitrile-0.1mol / L sodium acetate solution (pH adjusted to 6.5 with acetic acid) (7:93) as mobile phase A, acetonitrile-water (4:1) as mobile phase B, gradient elution (0-11min, 100%-93%A; 11-13.9min, 93%-88%A; 13.9-14min, 88%-85%A; 14-29min, 85%-66%A; 29-30min, 66%-0%A); flow rate was 1.0mL / min; detection wavelength was 254nm; column temperature was 43°C; injection volume was 5μL.

[0152] Preparation of reference solution: Accurately weigh 7.40 mg of L-hydroxyproline reference substance, 14.19 mg of glycine reference substance, 6.20 mg of alanine reference substance, and 7.18 mg of L-proline reference substance in a 10 mL volumetric flask, add 0.1 mol / L hydrochloric acid solution to prepare a mixed reference stock solution, accurately measure 0.1, 0.2, 0.4, 1, and 2 mL of the above mixed reference solution into a 10 mL volumetric flask, respectively, add 0.1 mol / L hydrochloric acid solution to the scale to obtain mixed reference solutions of a series of concentrations. Accurately measure 5 mL of the reference solution of the above series of concentrations and place it in a 25 mL volumetric flask, add 2.5 mL of 0.1 mol / L phenyl isothiocyanate (PITC) acetonitrile solution and 2.5 mL of 1 mol / L triethylamine acetonitrile solution, shake well, let it stand at room temperature for 1 hour, then dilute to the scale with 50% acetonitrile, take 10 mL, add 10 mL of n-hexane, shake, let it stand for 10 minutes, take the lower layer of solution, take the filtrate, and filter it through a 0.45 μm microporous filter membrane to obtain the product.

[0153] Preparation of test solution: Pipette 2mL of the paste to be tested into a 25mL volumetric flask, add 20mL of 0.1mol / L hydrochloric acid solution, ultrasonically treat for 30min, cool, dilute to the mark with 0.1mol / L hydrochloric acid solution, and shake well. Accurately measure 2mL, place in a 5mL ampoule, add 2mL of hydrochloric acid, hydrolyze at 150℃ for 1h, cool, transfer to an evaporating dish, wash with 10mL of distilled water in batches, add the washing liquid to the evaporating dish, evaporate to dryness, dissolve the residue in 0.1mol / L hydrochloric acid solution, transfer to a 25mL volumetric flask, add 0.1mol / L hydrochloric acid solution to the mark, shake well, and obtain. Measure 5mL of the above solution and operate according to the method under the preparation of the reference solution "Place in a 25mL volumetric flask, add 2.5mL of acetonitrile solution of 0.1mol / L phenyl isothiocyanate (PITC)" to obtain.

[0154] Determination: Accurately pipette 5ul of reference solution and 10ul of test solution respectively, inject into liquid chromatograph, and determine.

[0155] 2. Crocin Detection Method

[0156] 1. Chromatographic conditions

[0157] Chromatographic column: Agilent 5TC-C18 column (250 mm × 4.6 mm, 5 um);

[0158] Mobile phase: acetonitrile as mobile phase A, water as mobile phase B;

[0159] Elution method: Gradient elution as specified in the table below;

[0160] Time (minutes) Mobile phase A (%) Mobile phase B (%) 0～20 13 87 20～23 13→23 87→77 23～45 23→25 77→75 45～50 25→50 75→50

[0161] Detection wavelength: 440nm;

[0162] Flow rate: 1.0 mL / min;

[0163] Column temperature: 35 °C;

[0164] The injection volume was 10uL.

[0165] 2. Preparation of reference solution: Take appropriate amount of Crocin I and Crocin II, accurately determine the solution, and add dilute ethanol to prepare reference solution containing 30ug of Crocin I and 15ug of Crocin II per 1mL.

[0166] 3. Preparation of test solution: After the product is finely ground, take 0.5 g of the powder, accurately weigh it, put it in a stoppered conical flask, protect it from light, accurately add 50 mL of dilute ethanol, stopper it, weigh it, ultrasonicate it in an ice bath (power 500 W, frequency 40 kHz) for 30 min, let it cool to room temperature, weigh it again, make up the lost weight with dilute ethanol, shake it well, filter it, and take the filtrate to obtain the solution.

[0167] 4. Determination method

[0168] Accurately pipette 10ul of reference solution and test solution respectively, inject into liquid chromatograph, and measure to obtain the result.

[0169] 3. Detection method of salvianolic acid B content

[0170] 1. Chromatographic conditions

[0171] Chromatographic column: Agilent 5TC-C18 column (250 mm × 4.6 mm, 5 um);

[0172] Mobile phase: acetonitrile-0.2% phosphoric acid solution (24:76);

[0173] Column temperature: 25°C;

[0174] Flow rate: 1.2 ml per minute;

[0175] Detection wavelength: 286nm.

[0176] 2. Preparation of reference solution

[0177] Take an appropriate amount of Danpanic acid B reference substance, weigh it accurately, and add methanol-water (8:2) mixed solution to make a solution containing 0.10 mg per 1 ml.

[0178] 3. Preparation of test solution

[0179] Take about 1.0g of the powder of this product, accurately weigh it, put it in a stoppered conical flask, accurately add 50ml of methanol-water (8:2) mixed solution, stopper it, weigh it, ultrasonically treat it (power 140W, frequency 2kHz) for 30 minutes, let it cool, weigh it again, make up the lost weight with methanol-water (8:2) mixed solution, shake it well, filter it, accurately measure 5ml of the filtrate, transfer it to a 10ml volumetric flask, add methanol-water (8:2) mixed solution to dilute it to the scale, shake it well, filter it, and take the filtrate to obtain it.

[0180] 4. Assay

[0181] Accurately pipette 10ul of reference solution and test solution respectively, inject into liquid chromatograph, and measure to obtain the result.

[0182] 4. Dissolution Study Dissolution Conditions

[0183] Take the test sample and use 500mL of 0.1mol / L hydrochloric acid solution as the dissolution medium. After the temperature of the dissolution medium is constant at 37℃±0.5℃, take 15 pills of the test sample and put them into a dry rotating basket. Lower the rotating basket into the dissolution cup at a speed of 100r / min. Take 5mL of samples at 5min, 10min, 15min, 20min, 25min, 30min, 35min, 40min, 45min, and 50min respectively. Filter the solution into a round-bottom flask as the sample at the sampling time point; immediately add an equal volume of 37℃±0.5℃ constant temperature medium after sampling. The sample solution was evaporated to dryness, and 70 ml of methanol was added. The solution was refluxed until the extract was colorless. The methanol was recovered to dryness. The residue was added with 20 ml of ether and soaked for 3 minutes. The ether solution was poured off. The residue was transferred to a separatory funnel with 50 ml of n-butanol saturated with water in batches. The solution was extracted twice with 5 ml of ammonia test solution each time. The washing solution was combined. The solution was extracted twice with n-butanol saturated with water by shaking, each time with 10 ml of n-butanol solution. The solution was then washed twice with water saturated with n-butanol, each time with 10 ml of n-butanol solution. The water solution was combined. The solution was extracted by shaking with 15 ml of n-butanol saturated with water, each time with 10 ml of n-butanol solution. The solution was evaporated to dryness. The residue was transferred to a 50 ml volumetric flask with methanol and methanol was added to the mark. The solution was shaken well and filtered with a microporous filter membrane (0.45 μm). The filtrate was obtained.

[0184] 5. Chromatographic conditions for dissolution study

[0185] 1. Chromatographic conditions: Agilent C18 column (4.6 mm × 250 mm, 5 um); mobile phase: acetonitrile-water (35:65); flow rate: 1.0 mL / min; column temperature: 30 °C; detection wavelength: 203 nm; injection volume: 20 μl.

[0186] 2. Reference solution: Take an appropriate amount of ginsenoside Rb1 reference substance, accurately weigh 18.0 mg, add methanol to make a 1 ml solution containing 0.18 mg.

[0187] 3. Dissolution and dissolution curve detection: Take dissolution samples at different time points of 5min, 10min, 15min, 20min, 25min, 30min, 35min, 40min, 45min, and 50min, prepare them into test samples according to the above-mentioned treatment method, and measure them according to the determination method of ginsenoside Rb1 content in Yianning Pills, and record the peak area. Calculate the cumulative dissolution and dissolution curve (the calculation of cumulative dissolution and dissolution curve is based on the percentage value of the actual content of ginsenoside Rb1 in the pills).

[0188] Example 1-Example 5: Preparation of Ultrafiltration Filtrate of Turtle Shell Extract and Turtle Shell Clear Paste

[0189] The preparation method of the turtle shell extract ultrafiltration filtrate and the turtle shell clear paste comprises:

[0190] (1) Cleaning tortoise shells and turtle shells: steaming the tortoise shells and turtle shells for 60 minutes, then placing them in hot water to remove the rotten flesh in the tortoise shells and turtle shells, washing them with water, and drying them at low temperature or in the sun to obtain cleaned tortoise shells and turtle shells;

[0191] (2) decoction extraction: the tortoise shell and turtle shell cleaned in step (1) are crushed into pieces (the mass ratio of tortoise shell to turtle shell is 5:4), and water is added for decoction extraction for 3 times to obtain a water extract; each decoction extraction is for 24 hours, and the ratio of the total mass of the tortoise shell and turtle shell to the mass of water is 1:8 each time; the water extracts are combined, filtered (stainless steel filter or polyester filter with a pore size of 74um (200 mesh)), the filter residue is discarded, the supernatant is obtained by centrifugation, and microfiltration is performed to obtain an extract; the pore size of the filter membrane for microfiltration in step (2) is 2μm;

[0192] (3) Ultrafiltration: The extract obtained in step (3) is ultrafiltered to obtain a filtrate and an interception liquid; the filtrate obtained is the ultrafiltration filtrate of the turtle shell extract; the molecular weight cutoff of the ultrafiltration is shown in Table 1;

[0193] (4) Concentration: The intercepted liquid obtained in step (3) is subjected to membrane concentration (0.1nm-1nm reverse osmosis membrane) and low-temperature vacuum concentration to a solid content of 45wt% to obtain a turtle and tortoise shell clearing paste.

[0194] The total extraction rate of L-hydroxyproline, glycine, alanine and L-proline in the obtained turtle and tortoise shell paste (the percentage value obtained by dividing the total mass of L-hydroxyproline, glycine, alanine and L-proline by the total mass of the cleaned tortoise and turtle shells) and the gel strength and apparent viscosity of the obtained turtle and tortoise shell paste (tested according to GB6783-1994 method) were determined. The results are shown in Table 1.

[0195] Table 1: Ultrafiltration molecular weight cut-off investigation

[0196]

[0197] Example 6: Preparation of saffron pollen (crushing under low temperature and airtight conditions)

[0198] The saffron was crushed at a temperature of -16°C in a sealed condition to obtain saffron powder.

[0199] Example 7: Preparation of saffron pollen (crushing under normal temperature and non-sealed conditions)

[0200] The saffron is crushed at room temperature (about 30° C.) under non-sealed conditions to obtain saffron powder.

[0201] Example 8: Preparation of Danshen Powder (crushed under low temperature and airtight conditions)

[0202] The salvia miltiorrhiza was crushed at a temperature of -16°C in a sealed condition to obtain salvia miltiorrhiza powder.

[0203] Example 9: Preparation of Danshen Powder (crushed under normal temperature and non-sealed conditions)

[0204] The salvia miltiorrhiza is crushed under a non-sealed condition at room temperature (about 30° C.) to obtain salvia miltiorrhiza powder.

[0205] Example 10: Preparation of pills (saffron powder and salvia miltiorrhiza powder are both crushed under low temperature and sealed conditions, and the pill making method is the water-flooding pill method)

[0206] Prescription (by weight): 50 parts of American ginseng; 33 parts of dendrobium; 16 parts of cordyceps; 40 parts of turtle shell; 13 parts of velvet antler; 10 parts of schisandra; 10 parts of chicken gizzard; 50 parts of tortoise shell; 16 parts of saffron; 40 parts of panax notoginseng; 16 parts of ganoderma lucidum; 10 parts of snake gall; 10 parts of salvia miltiorrhiza; 16 parts of seahorse;

[0207] Take the above raw materials by weight and prepare according to the following preparation method:

[0208] Step S1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, one-fourth of the prescription amount of Dendrobium officinale, two-fourths of the prescription amount of Cordyceps sinensis, and one-fourth of the prescription amount of Hippocampus into fine powder, and mix them with a prescription amount of Salvia miltiorrhiza powder prepared according to the preparation method of Salvia miltiorrhiza powder described in Example 8 and a quarter of the prescription amount of saffron powder prepared according to the preparation method of saffron powder described in Example 6 to obtain a mixture A;

[0209] Step S2: Deer antler, ganoderma lucidum, snake gallbladder and the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron and the remaining prescription amount of seahorse as the medicinal materials to be decocted, add water and decoct twice, each time for 2 hours to obtain a decoction, combine the decoctions, filter (stainless steel filter or polyester filter with a pore size of 74um (200 mesh)) to obtain a filtrate, and mix the obtained filtrate with the ultrafiltration filtrate of tortoise shell extract prepared according to the preparation method described in Example 3 (the tortoise shell in the decoction and extraction step in Example 3 is 50 parts by weight and the turtle shell is 40 parts by weight), and concentrate to a relative density of 1.20-1.22 (relative to 25°C water, measured at 70°C) to obtain a clear paste B;

[0210] Step S3-1: Mix the mixture A obtained in step S1 and the clear paste B obtained in step S2, dry, crush, add water to make pills, dry, use the tortoise shell clear paste prepared according to the preparation method described in Example 3 (the tortoise shell in the decoction and extraction step in Example 3 is 50 parts by weight, and the tortoise shell is 40 parts by weight) as a coating adhesive, coat with 6 parts by weight of coating powder (red iron oxide mixed powder), polish (add insect white wax and roll in a sugar coating pan to polish), and obtain pills.

[0211] Example 11: Preparation of pills (saffron powder and salvia miltiorrhiza powder are crushed under low temperature and sealed conditions, and the pill making method is the plastic method)

[0212] Prescription (by weight): 50 parts of American ginseng; 33 parts of dendrobium; 16 parts of cordyceps; 40 parts of turtle shell; 13 parts of velvet antler; 10 parts of schisandra; 10 parts of chicken gizzard; 50 parts of tortoise shell; 16 parts of saffron; 40 parts of panax notoginseng; 16 parts of ganoderma lucidum; 10 parts of snake gall; 10 parts of salvia miltiorrhiza; 16 parts of seahorse;

[0213] Take the above raw materials by weight and prepare according to the following preparation method:

[0214] Step S1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, one-fourth of the prescription amount of Dendrobium officinale, two-fourths of the prescription amount of Cordyceps sinensis, and one-fourth of the prescription amount of Hippocampus into fine powder, and mix them with a prescription amount of Salvia miltiorrhiza powder prepared according to the preparation method of Salvia miltiorrhiza powder described in Example 8 and a quarter of the prescription amount of saffron powder prepared according to the preparation method of saffron powder described in Example 6 to obtain a mixture A;

[0215] Step S2: Deer antler, ganoderma lucidum, snake gallbladder and the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron and the remaining prescription amount of seahorse as the medicinal materials to be decocted, add water and decoct twice, each time for 2 hours to obtain a decoction, combine the decoctions, filter (stainless steel filter or polyester filter with a pore size of 74um (200 mesh)) to obtain a filtrate, and mix the obtained filtrate with the ultrafiltration filtrate of tortoise shell extract prepared according to the preparation method described in Example 3 (the tortoise shell in the decoction and extraction step in Example 3 is 50 parts by weight and the turtle shell is 40 parts by weight), and concentrate to a relative density of 1.20-1.22 (relative to 25°C water, measured at 70°C) to obtain a clear paste B;

[0216] Step S3-2: Mix the mixture A obtained in step S1 with the paste B obtained in step S2, make pills, dry, and use coating powder (mixed red iron oxide powder) and the tortoise shell paste prepared according to the preparation method described in Example 3 (the tortoise shell in the decoction and extraction step in Example 3 is 50 parts by weight, and the tortoise shell is 40 parts by weight) as a coating adhesive, coat with 6 parts by weight of coating powder (mixed red iron oxide powder), and polish (add insect white wax and roll in a sugar coating pan to polish) to obtain pills.

[0217] Example 12-Example 13, Comparative Example 2: Preparation of pills (Ultrafiltration filtrate of tortoise shell extract after ultrafiltration with different molecular weight cut-offs and tortoise shell clear paste)

[0218] Respectively replace the "turtle shell extract ultrafiltration filtrate prepared according to the preparation method described in Example 3" in Example 10 with the turtle shell extract ultrafiltration filtrate shown in Table 2, and replace the "turtle shell clear paste prepared according to the preparation method described in Example 3" in Example 10 with the turtle shell clear paste shown in Table 2, and the remaining operations are the same as those in Example 10, to obtain pills of Examples 12-13 and Comparative Example 2, respectively.

[0219] Table 2: Investigation of extraction methods of turtle shells

[0220]

[0221] Example 14: Preparation of pills (tortoise shell and turtle shell are decocted together with some other medicinal materials, and then the decocted tortoise shell and turtle shell are processed to prepare tortoise and turtle shell clear paste)

[0222] Prescription (by weight): 50 parts of American ginseng; 33 parts of dendrobium; 16 parts of cordyceps; 40 parts of turtle shell; 13 parts of velvet antler; 10 parts of schisandra; 10 parts of chicken gizzard; 50 parts of tortoise shell; 16 parts of saffron; 40 parts of panax notoginseng; 16 parts of ganoderma lucidum; 10 parts of snake gall; 10 parts of salvia miltiorrhiza; 16 parts of seahorse;

[0223] Take the above raw materials by weight and prepare according to the following preparation method:

[0224] Step P1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, Salvia miltiorrhiza, one-fourth of the prescription amount of Dendrobium officinale, two-fourths of the prescription amount of Cordyceps sinensis, one-fourth of the prescription amount of Hippocampus and one-fourth of the prescription amount of Saffron into fine powder, mix well, and obtain a mixture A;

[0225] Step P2: using velvet antler, ganoderma lucidum, snake gallbladder, the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron, the remaining prescription amount of seahorse and cleaned tortoise shell and turtle shell (steaming the tortoise shell and turtle shell for 60 minutes, then placing them in hot water to remove the rotten flesh in the tortoise shell and turtle shell, washing them with water, low-temperature drying or sun-drying to obtain the cleaned tortoise shell and turtle shell) as the medicinal materials to be decocted, adding water and decocting twice to obtain a decoction, combining the decoctions, filtering to obtain a filtrate, mixing the obtained filtrate with the tortoise shell extract ultrafiltration filtrate, concentrating to obtain a clear paste C;

[0226] Step P3: the tortoise shell and turtle shell boiled in step P2 are subjected to the operations of steps (2) to (4) of Example 3 to prepare a tortoise and turtle shell paste (i.e., the tortoise shell and turtle shell boiled in step P2 are substituted for the cleaned tortoise shell and turtle shell of Example 3 and the operations are performed);

[0227] Step P4: Mix the mixture A obtained in step P1 and the clear paste C obtained in step P2, dry, crush, add water to make pills, dry, coat with 6 parts by weight of coating powder (red iron oxide mixed powder) and the turtle shell clear paste obtained in step P3 as a coating adhesive, and polish to obtain the pills.

[0228] Example 15: Preparation of pills (crushing the saffron powder under normal temperature and non-sealed conditions)

[0229] Replace "one-fourth of the prescription amount of saffron pollen prepared according to the preparation method of saffron pollen described in Example 6" in Example 11 with "one-fourth of the prescription amount of saffron pollen prepared according to the preparation method of saffron pollen described in Example 7", and perform the remaining operations the same as in Example 11 to obtain pills.

[0230] Example 16: Preparation of pills (using salvia miltiorrhiza powder obtained by crushing under normal temperature non-sealed conditions)

[0231] Replace "the salvia miltiorrhiza powder prepared according to the preparation method of salvia miltiorrhiza powder described in Example 8" in Example 11 with "the salvia miltiorrhiza powder prepared according to the preparation method of salvia miltiorrhiza powder described in Example 9", and perform the remaining operations the same as in Example 11 to obtain pills.

[0232] Comparative Example 3: Preparation of pills (using refined honey as coating binder)

[0233] Prescription (by weight): 50 parts of American ginseng; 33 parts of dendrobium; 16 parts of cordyceps; 40 parts of turtle shell; 13 parts of velvet antler; 10 parts of schisandra; 10 parts of chicken gizzard; 50 parts of tortoise shell; 16 parts of saffron; 40 parts of panax notoginseng; 16 parts of ganoderma lucidum; 10 parts of snake gall; 10 parts of salvia miltiorrhiza; 16 parts of seahorse;

[0234] Take the above raw materials by weight and prepare according to the following preparation method:

[0235] Step S1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, one-fourth of the prescription amount of Dendrobium officinale, two-fourths of the prescription amount of Cordyceps sinensis, and one-fourth of the prescription amount of Hippocampus into fine powder, and mix them with a prescription amount of Salvia miltiorrhiza powder prepared according to the preparation method of Salvia miltiorrhiza powder described in Example 8 and a quarter of the prescription amount of saffron powder prepared according to the preparation method of saffron powder described in Example 6 to obtain a mixture A;

[0236] Step S2: Deer antler, ganoderma lucidum, snake gall, tortoise shell, turtle shell, and the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron and the remaining prescription amount of seahorse as the medicinal materials to be decocted, add water and decoct twice, each time for 2 hours to obtain a decoction, combine the decoctions, filter to obtain a filtrate, and concentrate the obtained filtrate to a relative density of 1.20-1.22 (relative to 25°C water, measured at 70°C) to obtain a clear paste C (the total extraction rate of L-hydroxyproline, glycine, alanine and L-proline in the clear paste C is 5%);

[0237] Step S3: mix the clear paste C obtained in step S2 with the mixture A obtained in step S1 and refined honey (the amount of refined honey added is the weight of the mixture A X 6 / 40) and water (the amount of water added is (the weight of the mixture A X 17 / 40) minus the weight of the clear paste C) to prepare pills, dry them, coat them with 6 parts by weight of coating powder (red iron oxide mixed powder) using refined honey as a coating adhesive, and polish them to obtain pills.

[0238] Conclusion: Compared with the clear paste C (Comparative Example 3) obtained by directly decocting tortoise shell and turtle shell together with other raw materials without ultrafiltration, the present invention decocts tortoise shell and turtle shell separately from other raw materials and performs ultrafiltration (Examples 3-5), and the obtained tortoise and turtle shell clear paste has a higher total extraction rate of L-hydroxyproline, glycine, alanine, and L-proline, and has a higher gel strength and apparent viscosity. This shows that the tortoise and turtle shell clear paste obtained by the treatment method of the present invention has a high collagen extraction rate, high gel strength and apparent viscosity, and can be used as a coating adhesive for pills.

[0239] Comparative Examples 4-6: Investigation of Coating Binders

[0240] Prepare according to the preparation method of Reference Example 10, replace the coating binder with an equal weight of the binder in Table 3, add water to mix until the coating binder concentration is 20wt%, then coat together with 6 parts by weight of coating powder (red iron oxide mixed powder), dry, and polish to obtain pills of Comparative Examples 4 to 6.

[0241] Table 3: Investigation of coating binders

[0242] Comparative Example Coating Binders Comparative Example 4 Glutinous rice flour paste Comparative Example 5 Gum Arabic Comparative Example 6 gelatin

[0243] Comparative Examples 7-9: Investigation of Adhesives and Coating Adhesives

[0244] Prepare by referring to the preparation method of Comparative Example 3, replace the refined honey in the pill-making process with an equal weight of the adhesive in Table 4, replace the coating adhesive with the coating adhesive in Table 4, add water to mix until the concentration of the coating adhesive is 20wt%, then coat together with 6 parts by weight of coating powder (red iron oxide mixed powder), dry, and polish to obtain the pills of Comparative Examples 7 to 9.

[0245] Table 4: Investigation of binders and coating binders

[0246] Comparative Example Adhesives Coating Binders Comparative Example 7 Glutinous rice flour paste Glutinous rice flour paste Comparative Example 8 Gum Arabic Gum Arabic Comparative Example 9 gelatin gelatin

[0247] Test Example 1: Dissolution Time Limit Investigation

[0248] The dissolution time of the pills obtained from Examples 10 to 14 and Comparative Examples 2 to 3 was checked according to the Chinese Pharmacopoeia. The results are shown in Table 5.

[0249] Table 5: Dissolution time

[0250]

[0251]

[0252] Conclusion: Compared with the preparation of pills using the turtle shell extract ultrafiltration filtrate and turtle shell paste obtained by ultrafiltration using other molecular weight cutoffs, the preparation of pills using the turtle shell extract ultrafiltration filtrate and turtle shell paste obtained by ultrafiltration using a molecular weight cutoff of 50kDa-100kDa (preferably 50kDa-60kDa) is more conducive to reducing the dissolution time of the obtained pills.

[0253] Test Example 2: Stability Study

[0254] The pills obtained in Examples 10 to 16 and Comparative Examples 2 to 6 were placed at high temperature (60° C.) for 10 days to detect the ginsenosides (ginsenoside Rg1(C 42 H 72 O 14)、ginsenoside Re(C 48 H 82 O 18 ), ginsenoside Rb1 (C54H92O23) and notoginsenoside R1 (C 47 H 80 O 18 ))’s total content at 0 days and the total content after being placed under high temperature conditions (60°C) for 10 days (the detection method refers to the detection method of Yi’anning Pills in “National Bureau of Drug Standards Promulgated Documents (2018.9.26)” (Standard No.: JZ20010027-2015Z-2018)), the results are shown in Table 6.

[0255] Table 6: Stability test results

[0256]

[0257]

[0258] in conclusion:

[0259] (1) The pellets prepared by the method provided by the present invention have good content stability.

[0260] (2) Compared with other coating adhesives, the use of the tortoise shell glue provided by the present invention as a coating adhesive is more conducive to improving the stability of the ginsenoside content of the obtained pills.

[0261] Test Example 3: Detection of crocin and salvianolic acid content

[0262] Procedure: The contents of crocin and salvianolic acid B in the pills obtained in Examples 10 to 16 and Comparative Examples 2 to 6 were respectively detected after being placed under high temperature conditions (60° C.) for 10 days. The results are shown in Table 7.

[0263] Table 7: Content detection and stability study of crocin and salvianolic acid

[0264]

[0265]

[0266] in conclusion:

[0267] (1) The present invention adopts low-temperature closed pulverization of Salvia miltiorrhiza and Crocus sativus (Example 10-Example 13), which is more conducive to increasing the content of crocin and salvianolic acid in the obtained pills, and has unexpected technical effects.

[0268] (2) Compared with other coating adhesives, the coating adhesive provided by the present invention is more conducive to improving the stability of the crocin and salvianolic acid B content of the obtained pills, and has unexpected technical effects.

[0269] Test Example 3: Dissolution and Dissolution Stability Study

[0270] The dissolution and dissolution curve of the pills obtained in Example 10-Example 11, Comparative Example 2, Comparative Example 7-Comparative Example 9 were tested at 0 day and placed under accelerated conditions (40°C ± 2°C, 75% RH ± 5%) for 6 months. The results are shown in Figure 1-Figure 6 .

[0271] in conclusion:

[0272] (1) Compared with other coating adhesives, the coating adhesive provided by the present invention is more conducive to improving the dissolution stability of the obtained pills, avoiding changes in the dissolution rate and dissolution curve of the obtained pills during transportation or storage, thereby affecting the bioavailability and product quality, and has unexpected technical effects.

[0273] (2) Compared with the preparation of pills by using turtle and tortoise shell paste obtained by other ultrafiltration cut-off molecular weights, the present invention preferably uses turtle and tortoise shell paste obtained by ultrafiltration with a cut-off molecular weight of 50 kDa-60 kDa to prepare pills, which is more conducive to improving the dissolution stability of the obtained pills, avoiding changes in the solubility and dissolution curve of the obtained pills during transportation or storage, thereby affecting the bioavailability and product quality, and has unexpected technical effects.

[0274] (3) The use of the coating adhesive provided by the present invention and the addition of the ultrafiltration filtrate of the tortoise shell extract to the clear paste B or the clear paste C are more conducive to improving the dissolution stability of the obtained pills, avoiding changes in the solubility and dissolution curve of the obtained pills during transportation or storage, thereby affecting the bioavailability and product quality, and having unexpected technical effects.

[0275] The method of the present invention has been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein within the content, spirit and scope of the present invention to implement and apply the technology of the present invention. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters. It is particularly important to point out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.

Claims

1. A drug, characterized in that The medicine is prepared from medicinal materials including American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallbladder, Dendrobium officinale, Cordyceps sinensis, Hippocampus, Pilose antler, Ganoderma lucidum, Snake gall, Salvia miltiorrhiza, Saffron, Tortoise shell and Turtle shell; The method for processing the tortoise shell and turtle shell includes extracting the active ingredients from the tortoise shell and turtle shell, and using new water to continue decocting and extracting the extracted tortoise shell and turtle shell, ultrafiltering, and concentrating to obtain a tortoise and turtle shell paste, and using the tortoise and turtle shell paste as the coating adhesive of the drug.

2. The medicine according to claim 1, wherein the tortoise shell and turtle shell are processed by: (1) Cleaning tortoise and turtle shells; (2) decoction extraction: decoct the cleaned tortoise shell and turtle shell in step (1), filter and microfilter to obtain an extract; (3) Ultrafiltration: Ultrafiltration the extract obtained in step (2) to obtain a filtrate and an interception liquid; the filtrate obtained is the ultrafiltration filtrate of the turtle shell extract; (4) Concentrating: concentrating the intercepted liquid obtained in step (3) to obtain the turtle and tortoise shell clearing paste; or The processing methods of the tortoise shell and the turtle shell include: (i) cleaning tortoise and turtle shells; (ii) decoction extraction: decoct the cleaned tortoise shell and turtle shell obtained in step (i) together with some other medicinal materials, filter and concentrate to obtain a clear paste C; (iii) continuing to decoct: replacing the tortoise shell and turtle shell decocted in step (ii) with new water and continuing to decoct, filtering, and microfiltering to obtain an extract; (iv) ultrafiltration: ultrafiltration the extract obtained in step (iii) to obtain a filtrate and an interception liquid; (v) Concentration: The intercepted liquid obtained in step (iv) is concentrated to obtain the turtle and tortoise shell clearing paste.

3. The drug according to claim 2, wherein the ultrafiltration molecular weight cut-off in step (3) is 50 kDa-100 kDa, preferably 50 kDa-60 kDa; and / or The pore size of the microfiltration membrane in step (2) is 0.1 μm-10 μm, preferably 1 μm-5 μm, more preferably 2 μm; and / or The pore size of the filter used in step (2) is 50 μm-150 μm or 74 μm; and / or The concentration in step (4) is carried out by membrane concentration and vacuum concentration; and / or The membrane concentration in step (4) is performed by using a nanofiltration membrane or a reverse osmosis membrane for concentration; and / or The pore size of the nanofiltration membrane in step (4) is 1 nm-2 nm; and / or The pore size of the reverse osmosis membrane in step (4) is 0.1 nm-1.0 nm; and / or The concentration in step (4) is to concentrate to a solid content of 40wt%-50wt%; and / or The ultrafiltration in step (iv) has a molecular weight cut-off of 50 kDa-100 kDa, preferably 50 kDa-60 kDa; and / or The pore size of the microfiltration membrane in step (iii) is 0.1 μm-10 μm, preferably 1 μm-5 μm, more preferably 2 μm; and / or The pore size of the filter in step (iii) is 50 μm-150 μm or 74 μm; and / or The concentration in step (v) is carried out by membrane concentration and vacuum concentration; and / or The membrane concentration in step (v) is performed by using a nanofiltration membrane or a reverse osmosis membrane; and / or The pore size of the nanofiltration membrane in step (v) is 1 nm to 2 nm; and / or The pore size of the reverse osmosis membrane in step (v) is 0.1 nm-1.0 nm; and / or The concentration in step (v) is performed to concentrate the solid content to 40 wt%-50 wt%.

4. The drug according to any one of claims 2 to 3, wherein step (2) comprises: The tortoise shell and turtle shell cleaned in step (1) are boiled in water for 1 to 5 times to obtain a water extract; Each decoction is performed for 12 to 48 hours, and the ratio of the total mass of the tortoise shell and the turtle shell to the mass of water is 1:5 to 1:15; the water extracts are combined, filtered and the residue is discarded, the supernatant is taken by centrifugation, and microfiltration is performed to obtain an extract; and / or The step (1) comprises: steaming tortoise shells and turtle shells, removing rotten flesh from the tortoise shells and turtle shells, washing with water, breaking into pieces, and obtaining cleaned tortoise shells and turtle shells; and / or The step (iii) comprises: adding water to the tortoise shell and turtle shell obtained after decoction in step (ii), and decocting and extracting for 1 to 5 times to obtain a water extract; each decoction and extraction takes 12 to 48 hours, and the ratio of the total mass of the tortoise shell and turtle shell to the mass of water is 1:5 to 1:15 each time; combining the water extracts, filtering and discarding the filter residue, centrifuging to obtain the supernatant, and microfiltering to obtain an extract; and / or The step (i) comprises: steaming tortoise shells and turtle shells, removing rotten flesh from the tortoise shells and turtle shells, washing with water, breaking into pieces, and obtaining cleaned tortoise shells and turtle shells.

5. The drug according to any one of claims 1 to 4, wherein the processing method of the tortoise shell and turtle shell comprises: (1) Cleaning tortoise and turtle shells: steaming tortoise and turtle shells, removing rotten flesh from the tortoise and turtle shells, washing with water, and breaking into pieces to obtain cleaned tortoise and turtle shells; (2) decoction extraction: the tortoise shell and turtle shell cleaned in step (1) are decocted and extracted 1 to 5 times to obtain a water extract; each decoction extraction takes 12 to 48 hours, and the ratio of the total mass of the tortoise shell and turtle shell to the mass of water is 1:5 to 1:15; the water extracts are combined, filtered and the filter residue is discarded, the supernatant is centrifuged and microfiltered to obtain an extract; the pore size of the filter membrane of the microfiltration in step (2) is 1 μm to 5 μm or 2 μm; (3) Ultrafiltration: Ultrafiltration the extract obtained in step (2) to obtain a filtrate and an interception liquid; the filtrate obtained is the ultrafiltration filtrate of the turtle shell extract; the ultrafiltration molecular weight cutoff is 50 kDa-100 kDa, preferably 50 kDa-60 kDa; (4) Concentration: The intercepted liquid obtained in step (3) is subjected to membrane concentration and low-temperature vacuum concentration to a solid content of 40 wt% to 50 wt%; Get the turtle and tortoise shell clearing ointment; or The processing methods of the tortoise shell and the turtle shell include: (i) cleaning tortoise shells and turtle shells: steaming the tortoise shells and turtle shells, removing the rotten flesh from the tortoise shells and turtle shells, washing with water, and breaking into pieces to obtain cleaned tortoise shells and turtle shells; (ii) decoction extraction: decoct the tortoise shell and turtle shell cleaned in step (i) together with some other medicinal materials, filter and concentrate to obtain a clear paste C; (iii) continuing to decoct: adding water to the tortoise shell and turtle shell decocted in step (ii) and decocting for 1 to 5 times to obtain a water extract; each decoction and extraction is for 12 to 48 hours, and the ratio of the total mass of the tortoise shell and turtle shell to the mass of water is 1:5 to 1:15; combining the water extracts, filtering and discarding the filter residue, centrifuging to obtain the supernatant, and microfiltering to obtain an extract; the pore size of the filter membrane of the microfiltration in step (iii) is 1 μm to 5 μm or 2 μm; (iv) ultrafiltration: ultrafiltration the extract obtained in step (iii) to obtain a filtrate and an interception liquid; the ultrafiltration molecular weight cut-off is 50 kDa-100 kDa, preferably 50 kDa-60 kDa; (v) Concentration: The intercepted liquid obtained in step (iv) is subjected to membrane concentration and low-temperature vacuum concentration to a solid content of 40 wt%-50 wt% to obtain a turtle and tortoise shell clearing paste.

6. The drug according to any one of claims 2 to 5, wherein the other medicinal materials in step (ii) are the whole amount of pilose antler, the whole amount of ganoderma lucidum, the whole amount of snake gallbladder, and one quarter to three quarters of the amount of dendrobium, one quarter to three quarters of the amount of cordyceps, one quarter to three quarters of the amount of saffron, and one quarter to three quarters of the amount of hippocampus; and / or In the preparation method of the drug, the salvia miltiorrhiza is added in the form of salvia miltiorrhiza powder, and the preparation method of the salvia miltiorrhiza powder comprises crushing the salvia miltiorrhiza at a temperature below -10°C and in a sealed condition; and / or The pulverizing step in the preparation method of the salvia miltiorrhiza powder comprises pulverizing under nitrogen or inert gas atmosphere; and / or In the preparation method of the drug, part of the prescribed amount of saffron is added in the form of saffron powder, and the remaining prescribed amount is added in the form of a decoction obtained by decocting and extracting saffron; and / or The method for preparing saffron powder comprises crushing saffron at a temperature below -10°C in a sealed condition; and / or The pulverizing step in the saffron pollen preparation method includes pulverizing under nitrogen or inert gas atmosphere.

7. The medicine according to any one of claims 1-6, which is prepared from the following medicinal materials in parts by weight: American ginseng 26.4-75.9, Panax notoginseng 16.5-62.7, Schisandra 1.65-16.5, Gallus gallbladder 1.65-16.5, Dendrobium 13.2-56.1, Cordyceps 3.3-29.7, Hippocampus 3.3-29.7, Pilose antler 1.65-16.5, Ganoderma lucidum 3.3-29.7, Snake gall 1.65-16.5, Salvia miltiorrhiza 1.65-26.4, Crocus 3.3-29.7, Tortoise shell 26.4-75.9 and Turtle shell 16.5-62.

7.

8. The drug according to any one of claims 1 to 7, which is in the form of a pill.

9. A method for preparing the drug according to any one of claims 1 to 8, comprising: Step S1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, a portion of the prescribed amount of Dendrobium officinale, a portion of the prescribed amount of Cordyceps sinensis and a portion of the prescribed amount of Hippocampus into fine powder, and mix them with Salvia miltiorrhiza powder and a portion of the prescribed amount of saffron powder to obtain a mixture A; the preparation method of the Salvia miltiorrhiza powder includes direct pulverization or preparation according to the preparation method of the Salvia miltiorrhiza powder in the medicine according to claim 6; the preparation method of the saffron powder includes direct pulverization or preparation according to the preparation method of the saffron powder in the medicine according to claim 6; Step S2: Add deer antler, ganoderma lucidum, snake gallbladder and the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron and the remaining prescription amount of seahorse as the medicinal materials to be decocted, add water and decoct for 1 to 5 times to obtain a decoction, combine the decoctions, filter to obtain a filtrate, mix the obtained filtrate with the ultrafiltration filtrate of the tortoise shell extract in step (2) of the medicine according to any one of claims 2 to 8, and concentrate to obtain a clear paste B; Step S3: Step S3-1: Mix the mixture A obtained in step S1 and the clear paste B obtained in step S2, dry, crush, add water to make pills, dry, coat with coating powder and use the turtle and tortoise shell clear paste in step (4) of the drug according to any one of claims 2 to 8 as a coating adhesive, and polish to obtain the drug; or Step S3-2: Mix the mixture A obtained in step S1 and the clear paste B obtained in step S2, make pills, dry, and coat with coating powder and the turtle and tortoise shell clear paste in step (4) of the drug according to any one of claims 1 to 8 as a coating adhesive, and polish to obtain the drug; Optionally, the partial prescription amount of Dendrobium in step S1 is one quarter to three quarters of the prescription amount of Dendrobium; and / or Optionally, the partial prescription amount of saffron in step S1 is one quarter to three quarters of the prescription amount of saffron; and / or Optionally, the partial prescription amount of hippocampus in step S1 is one quarter to three quarters of the prescription amount of hippocampus; and / or Optionally, the weight of water added each time water is added for decoction in step S2 is 5-15 times the total weight of the medicinal materials to be decocted; and / or Optionally, the decoction time of each decoction in step S2 is 1 hour to 5 hours; and / or Optionally, the concentration in step S2 is to concentrate to a clear paste B with a relative density of 1.20-1.22 at 70° C.; or The preparation method of the drug comprises: Step P1: Grind American ginseng, Panax notoginseng, Schisandra chinensis, Gallus gallus domesticus, a portion of the prescribed amount of Dendrobium officinale, a portion of the prescribed amount of Cordyceps sinensis and a portion of the prescribed amount of Hippocampus into fine powder, and mix them with Salvia miltiorrhiza powder and a portion of the prescribed amount of saffron powder prepared by the preparation method of saffron powder to obtain a mixture A; the preparation method of the Salvia miltiorrhiza powder includes direct pulverization or preparation according to the preparation method of the Salvia miltiorrhiza powder in the medicine according to claim 6; the preparation method of the saffron powder includes direct pulverization or preparation according to the preparation method of the saffron powder in the medicine according to claim 6; Step P2: using pilose antler, ganoderma lucidum, snake gallbladder, the remaining prescription amount of dendrobium, the remaining prescription amount of cordyceps sinensis, the remaining prescription amount of saffron, the remaining prescription amount of seahorse, and the cleaned tortoise shell and turtle shell obtained in step (i) of the drug according to any one of claims 2 to 8 as the medicinal materials to be decocted, adding water and decocting for 1 to 5 times to obtain a decoction, combining the decoctions, filtering to obtain a filtrate, mixing the obtained filtrate with the ultrafiltration filtrate of the tortoise shell extract, and concentrating to obtain a clear paste C; Step P3: preparing a tortoise and turtle shell paste by decocting the tortoise shell and turtle shell in step P2 according to steps (iii) to (v) of the medicine according to any one of claims 2 to 8; Step P4: Step P4-1: Mix the mixture A obtained in step P1 and the clear paste C obtained in step P2, dry, crush, add water to make pills, dry, coat with coating powder and use the turtle and tortoise shell clear paste obtained in step P3 as a coating adhesive, and polish to obtain the drug; or Step P4-2: Mix the mixture A obtained in step P1 and the clear paste C obtained in step P2, make pills, dry, and coat with coating powder using the turtle and tortoise shell clear paste obtained in step P3 as a coating adhesive, and polish to obtain the drug; Optionally, the partial prescription amount of Dendrobium in step P1 is one quarter to three quarters of the prescription amount of Dendrobium; and / or Optionally, the partial prescription amount of saffron in step P1 is one quarter to three quarters of the prescription amount of saffron; and / or Optionally, the partial prescription amount of hippocampus in step P1 is one quarter to three quarters of the prescription amount of hippocampus; and / or Optionally, the weight of water added each time water is added for decoction in step P2 is 5-15 times the total weight of the medicinal materials to be decocted; and / or Optionally, the decoction time of each decoction in step P2 is 1 hour to 5 hours; and / or Optionally, the concentration in step P2 is to concentrate to a clear paste C with a relative density of 1.20-1.22 at 70°C.

10. Use of the drug according to any one of claims 1 to 8 or the drug prepared by the preparation method according to claim 9 in the preparation of a drug for treating and / or coronary heart disease.

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