Pharmaceutical composition for preventing and treating ectopic calcification and preparation method thereof

Abstract

The invention relates to a pharmaceutical composition for preventing and / or treating ectopic calcification diseases and a preparation method thereof. Specifically, the invention provides a pharmaceutical composition which has certain compatibility and contains any two or three active ingredients A, B or C. The pharmaceutical composition disclosed by the invention can be used for effectively treating ectopic calcification diseases. On the basis, the invention provides a preparation method of the pharmaceutical composition and application of the pharmaceutical composition in preparation of drugs for treating and / or relieving ectopic calcification diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a pharmaceutical composition for preventing and / or treating ectopic calcification and a preparation method thereof. Background Art

[0002] Ectopic calcification is a disease in which calcium deposits occur in soft tissues outside physiological calcified tissues (usually referring to tissues such as teeth, bones, growth plates, articular cartilage, etc.). The process of physiological aging and some common diseases can promote its occurrence, thereby affecting health and even causing death. Such ectopic calcifications include senile cerebral calcification, calcification of bone joints and ligaments, gallstones, kidney stones, conjunctival calculi, calcification of periarthritis of shoulder, bladder calcification, prostatic calcification, cardiovascular calcification, placental calcification, etc.

[0003] In addition, ectopic calcification is also common in some genetic diseases, including idiopathic basal ganglia calcification, tumoral calcinosis, pseudoxanthoma elasticum, generalized arterial calcification of infancy, pulmonary alveolar microlithiasis, Keutel syndrome, arterial calcification due to CD73, etc.

[0004] The pathogenic mechanisms of these ectopic calcification diseases are mainly caused by abnormal metabolic calcification, dystrophic calcification, heterotopic ossification, etc. The specific underlying mechanisms have not been fully studied yet. And for different ectopic calcifications, there is currently no unified specific medicine clinically. Among the existing treatment methods for individual ectopic calcification diseases, the expected effects have not been achieved, and there are obvious drug toxic and side effects, or serious recurrence phenomena, or accompanied by great surgical pain, etc.

[0005] Intracranial calcification is a type of neurological disease with calcification in the brain as the main pathological feature. In 1850, Delacour first reported intracranial calcification. Subsequently, Bamberger et al. also reported intracranial calcification in a female patient with mental retardation and epileptic seizures, which pathologically confirmed the existence of intracranial calcification. In 1935, Fritzschie et al. described intracranial calcification radiologically. Intracranial calcification is very common clinically. According to statistics, the incidence rate of intracranial calcification is about 1%-20%, and the incidence rate increases with age.

[0006] Idiopathic basal ganglia calcification (IBGC) is an intracranial calcification caused by genetic factors, mainly characterized by symmetrical calcification in the basal ganglia and other parts of the brain, commonly known as Fahr disease. Most patients develop the disease between the ages of 30 and 60. Due to the calcification, symptoms such as Parkinson-like symptoms, ataxia, dystonia, dementia, memory decline, mental confusion, emotional disorders, epilepsy, and migraine often occur.

[0007] To date, in the research progress of the treatment of intracranial calcification, no effective treatment method has been found at home and abroad. In some individual literature reports, it is mentioned that etidronate disodium may have a relieving effect on the secondary symptoms of patients with intracranial calcification, but no reduction in calcium deposition in the patients' intracranial was found from CT images.

[0008] Therefore, there is an urgent need in this field to develop a drug composition for effectively treating ectopic calcification and intracranial calcification diseases and to study its preparation method. Summary of the Invention

[0009] The object of the present invention is to develop a drug composition for effectively treating ectopic calcification diseases and to study its preparation method. Specifically, the present invention provides a drug composition that can effectively treat ectopic calcification diseases and contains two or three medicinal materials selected from active ingredient A, B, or C. And its preparation method is provided.

[0010] In the first aspect of the present invention, a drug composition is provided, which contains two or three medicinal materials selected from the following group: active ingredient A, active ingredient B, or active ingredient C.

[0011] Among them, active ingredient A is selected from the following group: the root of Imperata cylindrica (L.) Beauv. or its extract;

[0012] Active ingredient B is selected from the following group: the seed kernel, root of Coix lacryma-jobi L. or its extract;

[0013] Active ingredient C is selected from the dried roots, leaves, fruits of any plant of the genus Glochidion or its extract.

[0014] In another preferred example, active ingredient C is the dried root of Glochidion puberum (L.) Hutch. or Glochidion wilsonii Hutch.

[0015] In another preferred example, the drug composition contains active ingredients A, B, and C;

[0016] Among them, the compatibility ratio of active ingredients A, B, and C is A:B:C = (1 to 84):(1 to 278):(1 to 140), preferably A:B:C = (1 to 15):(1 to 40):(1 to 20).

[0017] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 16:55:27.

[0018] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 83:278:139.

[0019] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 13:39:19.

[0020] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 17:54:26.

[0021] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 5:16:10.

[0022] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 1:1:1.

[0023] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 8:12:10.

[0024] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 2:8:6.

[0025] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 4:13:8.

[0026] In another preferred example, the pharmaceutical composition contains two medicinal materials selected from active ingredient A, active ingredient B, and active ingredient C;

[0027] Among them, when the pharmaceutical composition contains active ingredients A and B, their compatibility ratio is: A:B = (1 - 84):(1 - 278), preferably: A:B = 83:278;

[0028] Among them, when the pharmaceutical composition contains active ingredients A and C, their compatibility ratio is: A:C = (1 - 84):(1 - 140), preferably: A:C = 83:139;

[0029] Among them, when the pharmaceutical composition contains active ingredients B and C, their compatibility ratio is: B:C = (1 - 278):(1 - 140), preferably: B:C = 278:139.

[0030] In another preferred example, the active ingredient A is the dried root of Imperata cylindrica.

[0031] In another preferred example, the raw material active ingredient B is the dried root of Coix lacryma-jobi.

[0032] In another preferred example, the raw material active ingredient C is the dried root of any species of the genus Glochidion, preferably the dried root of Glochidion puberum or Glochidion wilsonii.

[0033] In another preferred example, the pharmaceutical composition further comprises other pharmaceutically acceptable solvents or excipients.

[0034] The second aspect of the present invention provides a medicine box, which comprises:

[0035] (a) a first container, and the pharmaceutical composition described in the first aspect of the present invention or a drug containing the pharmaceutical composition described in the first aspect of the present invention located in the first container; and

[0036] (b) a pharmaceutically acceptable carrier.

[0037] In another preferred example, the drug in the first container is a single-agent preparation containing the pharmaceutical composition described in the first aspect of the present invention.

[0038] In another preferred example, the dosage form of the drug is selected from the group consisting of: capsules, tablets, granule preparations, liquid preparations, or combinations thereof.

[0039] In another preferred example, the dosage form of the drug is an oral dosage form.

[0040] In another preferred example, the kit further contains an instruction manual.

[0041] In the third aspect of the present invention, there is provided the use of the pharmaceutical composition described in the first aspect or a preparation containing the pharmaceutical composition or the medicine box described in the second aspect of the present invention for preparing a drug for preventing and / or treating and / or alleviating ectopic calcification diseases and their related complications.

[0042] In another preferred example, the drug is also used for inhibiting calcification deposition.

[0043] In another preferred example, the ectopic calcification diseases are selected from the group consisting of: intracranial calcification, kidney stones, eye stones, calcification of scapulohumeral periarthritis, bladder calcification, prostate calcification, or combinations thereof; the complications of the intracranial calcification diseases are selected from the group consisting of: Parkinson-like symptoms, ataxia, dystonia, dementia, memory decline, mental confusion, emotional disorder, epilepsy, migraine, or combinations thereof.

[0044] In another preferred example, the preparation is an oral preparation or a non-oral preparation

[0045] In another preferred example, the preparation is a decoction.

[0046] In a fourth aspect of the present invention, there is provided a use of the pharmaceutical composition as described in the first aspect, or a preparation containing the pharmaceutical composition, or the kit as described in the second aspect of the present invention, for preparing a medicament for preventing and / or treating and / or alleviating intracranial calcification diseases.

[0047] In another preferred example, the medicament is also used for inhibiting intracranial calcification deposition.

[0048] In a fifth aspect of the present invention, there is provided a method for preparing the pharmaceutical composition as described in the first aspect, comprising the steps of:

[0049] (1) Providing a first mixture of any two or three selected from active ingredients A, B, and C, and decocting with water;

[0050] (2) Obtaining the decoction, and the obtained decoction is the pharmaceutical composition.

[0051] In another preferred example, the specific steps of decocting with water include:

[0052] (c1) Soaking the first mixture for 0.5 - 1 hour;

[0053] (c1) Decocting 2 - 3 times to obtain a crude decoction.

[0054] In another preferred example, the amount of water added is such that the water just submerges the first mixture.

[0055] In another preferred example, filtering the crude decoction in (c1) to obtain the decoction in step (2), which is the composition.

[0056] In another preferred example, before step (1), there is also the step of: taking the roots of any two or three selected from raw medicinal materials A, B, or C, washing, drying in the sun, pulverizing, and mixing to obtain the first mixture.

[0057] In another preferred example, when the first mixture contains active ingredients A, B, and C, the compatibility ratio of A, B, and C is: A:B:C = (1 - 84):(1 - 278):(1 - 140), preferably: A:B:C = (1 - 15):(1 - 40):(1 - 20), more preferably: A:B:C = 16:55:27.

[0058] In another preferred example, the first mixture contains two raw medicinal materials selected from A, B, or C; wherein

[0059] When containing active ingredients A and B, the compatibility ratio of each raw medicinal material is: A:B = (1 - 84):(1 - 278);

[0060] When containing active ingredients A and C, the compatibility ratio of each raw medicinal material is: A:C = (1 - 84):(1 - 140);

[0061] When active ingredients B and C are included, the compatibility ratio of each raw medicinal material is: B:C = (1 - 278):(1 - 140).

[0062] In the sixth aspect of the present invention, there is provided a method for preventing and / or treating and / or alleviating ectopic calcification diseases, by administering to a patient in need a pharmaceutically effective amount of the pharmaceutical composition described in the first aspect.

[0063] In another preferred example, the patient is a patient with intracranial calcification disease.

[0064] In the seventh aspect of the present invention, there is provided a method for preventing and / or treating and / or alleviating intracranial calcification disease, by administering to a patient in need a pharmaceutically effective amount of the pharmaceutical composition described in the first aspect.

[0065] In another preferred example, the patient is a patient with intracranial calcification disease.

[0066] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (such as in the examples) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be elaborated one by one here. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Figure 1 It is a diagram for grading the degree of cerebral calcification in intracranial calcification model mice. As Figure 1 shown, different degrees of intracranial calcification in intracranial calcification model mice are graded. The diagrams (a), (b), (c), (d), (e) and (f) are respectively Von kossa staining diagrams of brain slices of intracranial calcification model mice at different ages of 80 days, 90 days, 120 days, 180 days, 240 days and 300 days. The arrow indicates the calcification deposit, and the target value is 200 microns; the diagram (g) is a statistical chart of the calcification level index of the diagrams (a)-(f); the diagram (h) is a statistical chart of the calcification level of the diagram (g); Figure 1 In (g) and (h), there are 6 mice in each group.

[0068] Figure 2 It is a diagram of the degree of calcification of wild-type mouse water-fed group (WT + H2O), intracranial calcification model mouse water-fed group (Ki + H2O), intracranial calcification model mouse traditional Chinese medicine-fed group (Ki + LJY-001), and intracranial calcification model mouse high-dose ratio traditional Chinese medicine-fed group [Ki + LJY-001(high)] in each experimental group. As Figure 2As shown, the schematic diagrams of HE staining of brain sections of mice in the WT+H2O group, Ki+H2O group, Ki+LJY-001 group, and Ki+LJY-001(high) group are shown in Figures (a), (b), (c), and (d) respectively, with a target value of 200 microns; Figure (e) is a statistical chart of the calcification level index of Figures (a), (b), (c), and (d); Figure (f) is a statistical chart of the calcification level of Figure (e); there are 12 mice in each group in Figures (e) and (f); *p<0.05, ***p<0.001 are the results of t-tests.

[0069] Figure 3 The HE staining diagrams of the main tissues (heart, liver, spleen, lung, kidney, and femur) of mice in the WT+H2O group, Ki+H2O group, and Ki+LJY-001 group of each experimental group are shown. As Figure 3 shown, the HE staining diagrams of the sections of the WT+H2O group, Ki+H2O group, and Ki+LJY-001 group of mouse hearts are shown in Figures (a), (b), and (c) respectively; the HE staining diagrams of the sections of the WT+H2O group, Ki+H2O group, and Ki+LJY-001 group of mouse livers are shown in Figures (d), (e), and (f) respectively; the HE staining diagrams of the sections of the WT+H2O group, Ki+H2O group, and Ki+LJY-001 group of mouse spleens are shown in Figures (g), (h), and (i) respectively; the HE staining diagrams of the sections of the WT+H2O group, Ki+H2O group, and Ki+LJY-001 group of mouse lungs are shown in Figures (j), (k), and (l) respectively; the HE staining diagrams of the sections of the WT+H2O group, Ki+H2O group, and Ki+LJY-001 group of mouse kidneys are shown in Figures (m), (n), and (o) respectively; the HE staining diagrams of the sections of the WT+H2O group, Ki+H2O group, and Ki+LJY-001 group of mouse femurs are shown in Figures (p), (q), and (r) respectively; the target value in Figures (a) to (o) is 50 microns, and the target value in Figures (p) to (r) is 500 microns.

[0070] Figure 4 The diagrams of the calcification degree of the water-fed groups [Ki+H2O(21.5 weeks)] of intracranial calcification model mice at 21.5 weeks of age, the water-fed groups [Ki+H2O(30 weeks)] of intracranial calcification model mice at 30 weeks of age, and the drug-fed groups [Ki+LJY-001(21.5-30 weeks)] of intracranial calcification model mice between 21.5 weeks and 30 weeks of age in each experimental group are shown. As Figure 4 shown, the schematic diagrams of HE staining of brain sections of mice in the Ki+H2O(21.5 weeks) group, Ki+H2O(30 weeks) group, and Ki+LJY-001(21.5-30 weeks) group are shown in Figures (a), (b), and (c) respectively, with a target value of 200 microns; Figure (d) is a statistical chart of the calcification level of Figures (a), (b), and (c), with 5 mice in each group in the figure, and the p value is the result of ANOVA test.

[0071] Figure 5 For the calcification degree diagrams of the wild-type mouse water-fed group (WT+H2O), intracranial calcification model mouse water-fed group (Ki+H2O), traditional Chinese medicine group for intracranial calcification model mice fed with the dose ratio of Chinese medicinal materials B and C [Ki+LJY-001(BC)], traditional Chinese medicine group for intracranial calcification model mice fed with the dose ratio of Chinese medicinal materials A and C [Ki+LJY-001(AC)], and traditional Chinese medicine group for intracranial calcification model mice fed with the dose ratio of Chinese medicinal materials A and B [Ki+LJY-001(AB)] in the pairwise compatibility experiment of raw medicinal materials. As Figure 5 shown, (a), (b), (c), (d), and (e) are respectively the schematic diagrams of HE staining of brain sections of mice in the WT+H2O group, Ki+H2O group, Ki+LJY-001(BC) group, Ki+LJY-001(AC) group, and Ki+LJY-001(AB) group, and the target value is 200 microns; the diagram (f) is the statistical chart of the calcification levels of the mice in the above groups (a)-(e), with 12 mice in each group; *p<0.05, **p<0.005 are the results of t-tests.

[0072] Figure 6 Brain CT imaging diagram of the intracranial calcification patient Liu. The white area in the brain pointed by the black arrow is calcium deposition. Detailed implementation manners

[0073] Through extensive and in-depth research, the inventor of the present invention unexpectedly discovers for the first time that a pharmaceutical composition containing two or three selected from the active ingredients A, B, or C can effectively prevent and / or treat and / or relieve ectopic calcification diseases and their related complications. Ectopic calcification diseases include: intracranial calcification, kidney stones, eye stones, calcification of periarthritis of shoulder, bladder calcification, prostate calcification; complications of intracranial calcification diseases include: Parkinson-like symptoms, ataxia, dystonia, dementia, memory decline, mental confusion, emotional disorder, epilepsy, migraine, etc. On this basis, the present invention is completed.

[0074] Specifically, the present invention provides a pharmaceutical composition. When the pharmaceutical composition of the present invention contains the active ingredients A, B, and C, the compatibility ratio of A, B, and C is A:B:C=(1-84):(1-278):(1-140), preferably A:B:C=(1-15):(1-40):(1-20). The pharmaceutical composition of the present invention can effectively treat and / or relieve ectopic calcification diseases and their related complications;

[0075] When the pharmaceutical composition of the present invention contains the active ingredients A and B, the compatibility ratio thereof is: A:B=(1-84):(1-278), preferably: A:B=83:278. The pharmaceutical composition of the present invention can effectively treat and / or relieve ectopic calcification diseases and their related complications;

[0076] When the pharmaceutical composition of the present invention contains active ingredients A and C, the compatibility ratio is: A:C = (1 - 84):(1 - 140), preferably: A:C = 83:139. The pharmaceutical composition of the present invention can effectively treat and / or relieve ectopic calcification diseases and their related complications;

[0077] When the pharmaceutical composition of the present invention contains active ingredients B and C, the compatibility ratio is: B:C = (1 - 278):(1 - 140), preferably: B:C = 278:139. The pharmaceutical composition of the present invention can effectively treat and / or relieve ectopic calcification diseases and their related complications.

[0078] On this basis, the present invention also provides a method for preparing the pharmaceutical composition of the present invention.

[0079] The term

[0080] Ectopic calcification disease

[0081] Ectopic calcification is a disease in which calcium deposits appear in soft tissues outside physiological calcified tissues (usually referring to tissues such as teeth, bones, growth plates, articular cartilage, etc.). The process of physiological aging and some common diseases can promote its occurrence, which in turn affects health and even causes death. Such ectopic calcifications include intracranial calcification, calcification of bone joint ligaments, gallstones, kidney stones, eye stones, calcification of periarthritis of shoulder, bladder calcification, prostate calcification, cardiovascular calcification, placental calcification, etc.

[0082] Intracranial calcification disease

[0083] Intracranial calcification is a type of neurological disease with calcium deposition in the brain as the main pathological feature, which can be divided into two types: physiological calcification and pathological calcification. If the calcification is only limited to the globus pallidus, does not involve other parts of the brain, and the patient does not show neurological symptoms after the age of 40 and has no calcium metabolism disorder diseases, it can be regarded as intracranial physiological calcification; while pathological calcification can be caused by many factors, such as genetic factors, TORCH syndrome, viral infection, trauma, toxins, physiological injury, aging, hypoparathyroidism, etc. In addition, many congenital syndromes can also be accompanied by brain calcification, such as Aicardi-Goutières syndrome, Cockayne syndrome, type I Kenny-Caffey syndrome, Krabbe disease, etc.

[0084] Kidney stone

[0085] Kidney stones are a type of ectopic calcification (mainly calcium oxalate or calcium phosphate) that abnormally accumulates in the kidneys and is a common cause of abdominal and groin pain and hematuria. One in every 11 people will experience this condition at some point in their lives, and the number of male patients is twice that of female patients. The occurrence of kidney stones is related to a decrease in urine volume or an increase in the excretion of stone components (such as calcium, phosphorus, oxalic acid, uric acid, cystine, xanthine, and phosphate). Low citrate content or high acidity in urine may also cause kidney stones. Kidney stones present as unbearable pain, and most patients who come to the emergency department are in great pain. Single kidney stones do not cause renal failure, but recurrent kidney stones can damage the renal tubular epithelial cells, leading to the loss of renal parenchymal function. Currently, the main methods for treating kidney stones include drinking a large amount of water, taking lithotriptic drugs, appropriate exercise, and surgical operations. A traditional Chinese medicine composition discovered in the present invention can effectively remove kidney stones in the kidneys and relieve pain after being taken by patients with kidney stones, with remarkable curative effects.

[0086] Ocular calculi

[0087] Ocular calculi are a type of multiple hard masses that occur on the palpebral conjunctiva and are related to the accumulation of epithelial cells and the compression of mucus to produce degenerated products. When the ocular calculi protrude, it will cause a foreign body sensation in the patient's eyes and even corneal abrasion and erosion, which are more common in middle-aged and elderly people and patients with other ophthalmic diseases. A traditional Chinese medicine composition discovered in the present invention can expel the calculi growing in the eyelids after being taken by patients with ocular calculi, with remarkable curative effects.

[0088] Calcification of periarthritis of shoulder

[0089] Calcification of periarthritis of shoulder refers to the inflammation of the shoulder soft tissues caused by periarthritis of shoulder. Long-term inflammatory stimulation further induces ectopic calcification such as tendon calcification and osteoproliferation of the shoulder joint, presenting symptoms such as shoulder joint pain and limited movement. A traditional Chinese medicine composition discovered in the present invention can relieve the pain of the shoulder joint and restore movement after being taken by patients with calcification of periarthritis of shoulder.

[0090] Bladder calcification

[0091] Bladder calcification refers to the deposition of calcium in the bladder mucosa or its muscular layer. If not treated in time, it will promote the occurrence and development of diseases such as kidney stones and urinary tract stones.

[0092] Prostatic calcification

[0093] Prostatic calcification refers to the deposition of calcium in the prostatic ducts and prostatic acini, and then the formation of true stones, which is one of the common prostatic lesions in men.

[0094] Imperata cylindrica

[0095] As used herein, the term "Imperata cylindrica" refers to the Chinese medicinal herb Imperata cylindrica or its active extract. Imperata cylindrica (L.) Beauv. is the rhizome of the plant Imperata cylindrica Beauv. of the Gramineae family. Aliases: Imperata cylindrica root, orchid root, and root of Imperata cylindrica. Preferably, it is the dried root of Imperata cylindrica (L.) Beauv. var. major (Nees) C.E. Hubb. The Chinese medicinal herb Imperata cylindrica has functions such as clearing heat and promoting fluid production. In the present invention, Imperata cylindrica is also referred to as the first active ingredient A.

[0096] As used herein, the term "Coix lacryma-jobi" refers to the Chinese medicinal herb Coix lacryma-jobi or its active extract. Coix lacryma-jobi L. is the root, seed kernel, or a combination thereof of the plant Coix lacryma-jobi L. of the Gramineae family. Semen Coicis is the seed kernel of Coix lacryma-jobi. Aliases: Semen Coicis, Job's tears, coix seed, ditch seed, coix seed, etc. The functions of Coix lacryma-jobi root are basically the same as those of Semen Coicis. The Chinese medicinal herb Coix lacryma-jobi has functions such as strengthening the spleen and promoting diuresis, removing dampness obstruction, relieving diarrhea, and clearing heat. In the present invention, Coix lacryma-jobi is also referred to as the second active ingredient B.

[0097] As used herein, the term "Glochidion puberum" refers to the Chinese medicinal herb Glochidion puberum or its active extract. Glochidion puberum (L.) Hutch. is the root, leaf, fruit, or a combination thereof of the plant Glochidion of the Euphorbiaceae family. Representative plants of the genus Glochidion include (but are not limited to): Glochidion puberum (L.) Hutch., Glochidion wilsonii Hutch., etc. Aliases of Glochidion puberum include: Li Jizi, wild pumpkin, persimmon pepper, abacus beads, etc. The Chinese medicinal herb Glochidion puberum has functions such as clearing heat and promoting diuresis, expelling wind and activating collaterals. In the present invention, Glochidion puberum is also referred to as the third active ingredient C.

[0098] The pharmaceutical composition of the present invention

[0099] As used herein, the pharmaceutical composition of the present invention comprises two or three kinds of medicinal materials selected from the following group in a certain compatibility: active ingredient A, B, or C.

[0100] In another preferred embodiment, the compatibility ratio of active ingredients A, B, and C is A:B:C = (1 - 84):(1 - 278):(1 - 140), preferably A:B:C = (1 - 15):(1 - 40):(1 - 20).

[0101] In another preferred embodiment, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 16:55:27.

[0102] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 83:278:139.

[0103] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 13:39:19.

[0104] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 17:54:26.

[0105] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 5:16:10.

[0106] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 1:1:1.

[0107] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 8:12:10.

[0108] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 2:8:6.

[0109] In another preferred example, the compatibility ratio of the active ingredients A, B, and C is: A:B:C = 4:13:8.

[0110] In another preferred example, when the pharmaceutical composition of the present invention contains active ingredients A and B, its compatibility ratio is: A:B = (1 - 84):(1 - 278), preferably: A:B = 83:278;

[0111] In another preferred example, when the pharmaceutical composition of the present invention contains active ingredients A and C, its compatibility ratio is: A:C = (1 - 84):(1 - 140), preferably: A:C = 83:139;

[0112] In another preferred example, when the pharmaceutical composition of the present invention contains active ingredients B and C, its compatibility ratio is: B:C = (1 - 278):(1 - 140), preferably: B:C = 278:139.

[0113] In another preferred example, the active ingredient A is the dried root of Imperata cylindrica.

[0114] In another preferred example, the active ingredient B is the dried root of Coix lacryma-jobi.

[0115] In another preferred example, the active ingredient C is the dried root of any species of Glochidion, preferably the dried root of Glochidion puberum or Glochidion wilsonii.

[0116] In another preferred embodiment, the pharmaceutical composition further comprises other pharmaceutically acceptable solvents or excipients.

[0117] In another preferred embodiment, the pharmaceutical composition comprises a pharmaceutically acceptable carrier or excipient. Such carriers include (but are not limited to): saline, buffer solution, glucose, water, glycerol, ethanol, and combinations thereof. The pharmaceutical preparation should be matched with the administration route. The pharmaceutical composition of the present invention can be made into an injection form, for example, prepared by a conventional method with physiological saline or an aqueous solution containing glucose and other adjuvants. Pharmaceutical compositions such as tablets and capsules can be prepared by conventional methods. Pharmaceutical compositions such as injections and solutions should be manufactured under sterile conditions. The dosage of the active ingredient is a therapeutically effective amount, for example, about 1 μg / kg body weight - about 5 mg / kg body weight per day. In addition, the present invention can also be used in combination with other therapeutic agents.

[0118] When using the pharmaceutical composition, a safe and effective amount of the composition of the present invention is administered to a mammal, wherein the dosage of the active ingredient of the present invention is generally 0.001 mg / kg - 1000000 mg / kg body weight.

[0119] Of course, the specific dosage should also consider factors such as the administration route and the health status of the patient, which are within the scope of the skills of a skilled physician.

[0120] Preparation method

[0121] The present invention also provides a method for preparing the composition of the present invention, the method comprising the steps of:

[0122] (1) Provide a first mixture of any two or three selected from active ingredients A, B, and C, and decoct with water;

[0123] (2) Obtain the decoction, and the obtained decoction is the pharmaceutical composition.

[0124] In another preferred embodiment, the specific steps of decocting with water include:

[0125] (c1) Soak the first mixture for 0.5 - 1 hour;

[0126] (c1) Decoct 2 - 3 times to obtain a crude decoction.

[0127] In another preferred embodiment, the amount of water added is such that the water just submerges the first mixture.

[0128] In another preferred embodiment, filter the crude decoction in (c1) to obtain the decoction in step (2), which is the composition.

[0129] In another preferred example, before the step (1), there is further a step of taking any two or three roots selected from the raw medicinal materials A, B or C, washing, drying in the sun, pulverizing and mixing to obtain a first mixture.

[0130] The main advantages of the present invention are as follows:

[0131] (a) For the first time, a pharmaceutical composition containing two or three selected from the active ingredients A, B or C in a certain compatibility is provided.

[0132] (b) For the first time, the use of a pharmaceutical composition containing two or three selected from the active ingredients A, B or C in the preparation of a medicament for preventing and / or treating and / or alleviating ectopic calcification diseases (especially intracranial calcification diseases) is discovered.

[0133] (c) For the first time, it is publicly disclosed that when the pharmaceutical composition of the present invention contains the following ingredients and compatibility, it can effectively treat ectopic calcification diseases:

[0134] (c1) When the active ingredients are A, B, C, the compatibility ratio of A, B, C is A:B:C = (1 - 84):(1 - 278):(1 - 140), preferably A:B:C = (1 - 15):(1 - 40):(1 - 20),

[0135] (c2) When the active ingredients are A and B, their compatibility ratio is: A:B = (1 - 84):(1 - 278), preferably: A:B = 83:278,

[0136] (c3) When the active ingredients are A and C, their compatibility ratio is: A:C = (1 - 84):(1 - 140), preferably: A:C = 83:139,

[0137] (c4) When the active ingredients are B and C, their compatibility ratio is: B:C = (1 - 278):(1 - 140), preferably: B:C = 278:139.

[0138] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods without specific conditions noted in the following embodiments are usually in accordance with conventional conditions, such as the conditions described in Sambrook et al., Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989), or in accordance with the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.

[0139] Embodiment Materials and Preparation

[0140] Before the implementation of the examples, we constructed a model mouse for intracranial calcification disease (slc20a2-p.S602W ki mouse). The base CC at positions 1805-1806 of the cDNA of mouse slc20a2 gene [Ensembl Gene ID: (ENSMUSG00000037656)] (Transcript: slc20a2-201 (ENSMUST00000067786)) was mutated to GG, so that the codon TCC at position 602 was mutated to TGG, and the encoded serine was changed to tryptophan (p.S602W). Wild-type (WT), heterozygous (slc20a2 + / S602W ) and homozygous (slc20a2 S602W / S602W ) mice were obtained respectively. Through phenotypic analysis, we determined that the homozygous mice had extremely similar phenotypes to human intracranial calcification disease. Calcification phenotypes and other symptoms that progressively developed with age appeared in the brains of homozygous mice, such as abnormal motor balance ability, anxiety behavior, learning and memory, and depressive behavior. Therefore, we used the above-mentioned homozygous mice as intracranial calcification model mice (see Chinese Patent Application No.: 201810552675.5).

[0141] Example 1 Effects of the traditional Chinese medicine composition of the present invention on intracranial calcification in mice

[0142] 1.1 Establishment of different levels of intracranial calcification in intracranial calcification model mice

[0143] It is known that the degree of intracranial calcification in intracranial calcification model mice worsens with age. For the convenience of statistics, the degree of cerebral calcification in mice was graded. First, the area of the sagittal plane along the midline of the brain of 90-day-old mice was taken as a unit; then, the calcified area in the serial sections of the sagittal plane of the brains of the mice to be evaluated was counted, and the ratio of the calcified area to the unit area was used as the evaluation criterion for the calcification level of the mice:

[0144] Calcification level index = calcified area ÷ unit area

[0145] At the same time, we selected the maximum value among the calcification levels of the serial sections of the brain of the same mouse as the total calcification level of this mouse. We divided the calcification level into six levels from 0 to 5, and the corresponding relationship between the calcification level index is as follows:

[0146] Level 0 = 0, 0 < Level 1 ≤ 0.00005, 0.00005 < Level 2 ≤ 0.00015, 0.00015 < Level 3

[0147] ≤ 0.0003, 0.0003 < Level 4 ≤ 0.0005, Level 5 > 0.0005( Figure 1 , a-h). The specific method is as follows:

[0148] (1) Preparation of paraffin sections

[0149] Tissue collection: The mice were anesthetized with 10% chloral hydrate, fixed on the dissection board, the chest cavity was opened, the perfusion needle was inserted into the left ventricle, and a small incision was made in the right auricle. First, perfusion was performed with normal saline, and after the blood completely flowed out, it was replaced with 4% paraformaldehyde for perfusion (15 minutes). Then, the target tissue (brain) was removed and placed in 4% paraformaldehyde solution for overnight fixation.

[0150] Dehydration: The tissues were placed in 75% alcohol for 4 hours, 85% alcohol for 2 hours, 90% alcohol for 2 hours, 95% alcohol for 1 hour, absolute ethanol I for 30 minutes, absolute ethanol II for 30 minutes, alcohol-benzene for 5 - 10 minutes, xylene I for 5 - 10 minutes, xylene II for 5 - 10 minutes, wax I for 1 hour, wax II for 1 hour, and wax III for 1 hour.

[0151] Embedding: The tissues impregnated with wax were embedded in an embedding machine. First, the melted wax was put into the embedding frame. Before the wax solidified, the tissues were taken out of the dehydration box, placed in the embedding frame according to the requirements of the embedding surface, and the corresponding labels were attached. After cooling, when the wax solidified, the wax blocks were taken out of the embedding frame and trimmed.

[0152] Sectioning: The trimmed wax blocks were sectioned on a paraffin microtome with a thickness of 5 μm. The sections were floated on warm water at 40°C on a spreading table to flatten the tissues, picked up with glass slides, and baked in an oven at 60°C.

[0153] (2) Von kossa staining

[0154] The dewaxed-to-water sections were incubated in 5% sodium thiosulfate solution for 30 minutes, rinsed with distilled water, stained with 1% silver nitrate solution under ultraviolet light for 30 minutes, rinsed with distilled water to remove the black substances floating on the surface of the sections, further counterstained with 5% sodium thiosulfate for 2 minutes, stained with 1% neutral red for 10 minutes, and finally dehydrated, cleared, and sealed with neutral balsam. Both 5% sodium thiosulfate and 1% silver nitrate solutions were prepared freshly before use.

[0155] (3) HE staining

[0156] HE staining (hematoxylin-eosin staining): After preparing tissue paraffin sections, dewax the paraffin sections to water: sequentially place the sections in xylene I for 20 minutes, xylene II for 20 minutes, absolute ethanol I for 10 minutes, absolute ethanol II for 10 minutes, 95% alcohol for 5 minutes, 90% alcohol for 5 minutes, 80% alcohol for 5 minutes, 70% alcohol for 5 minutes, and distilled water wash for 2 minutes. Stain cell nuclei with hematoxylin: Immerse the sections in hematoxylin for 3 - 8 minutes, rinse with tap water, differentiate with 1% hydrochloric acid alcohol for 8 - 10 seconds, rinse with tap water, blue with 0.6% ammonia water, and rinse with running water. Stain cytoplasm with eosin: Immerse the sections in eosin staining solution for 1 - 3 minutes. Dehydrate and mount the slides: sequentially place the sections in 95% alcohol I for 5 minutes - 95% alcohol II for 5 minutes - absolute ethanol I for 5 minutes - absolute ethanol II for 5 minutes - xylene I for 5 minutes - xylene II for 5 minutes for dehydration and clearing. After taking out the sections from xylene and slightly air-drying them, mount the slides with neutral gum.

[0157] (4) Statistical analysis of calcification area

[0158] Make continuous paraffin sections (5 μm thick) of the embedded mouse brains, and then perform Von kossa staining or HE staining. Select the section with the most severe calcification by microscopic observation, take pictures with an Olympus BX53 microscope, and quantitatively analyze the calcification area in the taken pictures using Image-ProPlus 6.0 Software (the ratio of the statistical unit to the area in the software is 1 pixel = 0.47 square micrometers).

[0159] 1.2 Animal experiments on the traditional Chinese medicine composition with optimized weight ratio

[0160] Method

[0161] The drug for preventing and treating ectopic calcification diseases used in this example is: the raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion puberum. According to the compatibility ratio of Imperata cylindrica: Coix lacryma-jobi: Glochidion puberum = 16:55:27, take 4 grams of Imperata cylindrica, 13.75 grams of Coix lacryma-jobi, and 6.75 grams of Glochidion puberum. Wash, dry, and pulverize the raw medicinal materials, place them in a container, add water to cover the medicinal materials, decoct twice. Decoct for 60 minutes for the first time and 30 minutes for the second time. Filter the decoction liquid, combine and mix the decoction liquid obtained from each decoction to obtain a combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 2900 ml for experimental administration to the drug administration group in the following mouse experiments.

[0162] Separate groups of WT+H2O, Ki+H2O, and Ki+LJY-001 were designed. Six male and six female wild-type mice were selected for the WT+H2O group, and sterile water was used as the drinking water as a control. Six male and six female mice with intracranial calcification models were selected for the Ki+H2O group, and sterile water was used as the drinking water as a control. Six male and six female mice with intracranial calcification models were selected for the Ki+LJY-001 group, and the medicinal liquid decocted from the traditional Chinese medicine composition of the present invention was administered. Each mouse was given 7 milliliters of the medicinal liquid per day. The experiment started at the 4th week after the mice were born (the weaning time of the mice) and lasted for 27 weeks. When the mice in each group reached 30 weeks of age, six male and six female mice were respectively selected. By making continuous paraffin sections of the mouse brains, the intracranial calcification conditions of the mice were observed and counted.

[0163] Results

[0164] Compared with the Ki+H2O group, the degree of intracranial calcification in the intracranial calcification model mice in the Ki+LJY-001 group was significantly reduced ( Figure 2 , a-f), indicating that the traditional Chinese medicine composition of the present invention effectively inhibits the formation and development of intracranial calcification in intracranial calcification model mice.

[0165] 1.3 Animal toxicity experiment of the drug of the present invention

[0166] Method

[0167] The tissue sections of the hearts, livers, spleens, lungs, kidneys, and femurs of the mice in the above-mentioned WT+H2O, Ki+H2O, and Ki+LJY-001 groups were stained with HE for observation.

[0168] Results

[0169] It was found that there were no obvious differences in the hearts, livers, spleens, lungs, kidneys, femurs, etc. of the mice in the three groups ( Figure 3 , a-r), indicating that there are no obvious side effects when the intracranial calcification model mice take the traditional Chinese medicine composition with this optimized dosage ratio for a long time.

[0170] Example 2

[0171] Animal experiment of the traditional Chinese medicine composition with the preferred weight ratio of raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum (specifically Glochidion puberum)

[0172] Method

[0173] The drug for preventing and treating ectopic calcification used in this example is as follows: The raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion puberum. According to the compatibility ratio of Imperata cylindrica: Coix lacryma-jobi: Glochidion puberum = 16:55:27, take 4 grams of Imperata cylindrica, 13.75 grams of Coix lacryma-jobi, and 6.75 grams of Glochidion puberum as raw medicinal materials. Wash, dry, and crush them, place them in a container, add water to cover the medicinal materials, decoct twice. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, and combine and mix the decoction liquid obtained from each decoction to obtain a combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 2900 milliliters for experimental administration to the drug-administered group in the following mouse experiment.

[0174] Results

[0175] The degree of calcification of the mice in the drug-administered group was comparable to that of the traditional Chinese medicine group in Example 1 in the mouse experiment conducted by the method of Example 1.

[0176] Effect of the drug of the present invention with a high weight ratio on intracranial calcification in mice

[0177] 3.1 Animal experiment of the drug of the present invention with a high weight ratio

[0178] Method

[0179] The drug for preventing and treating ectopic calcification diseases used in this example is as follows: The raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion puberum var. hupehense. According to the high weight compatibility ratio of Imperata cylindrica: Coix lacryma-jobi: Glochidion puberum = 83:278:139, take 8.3 grams of Imperata cylindrica, 27.8 grams of Coix lacryma-jobi, and 13.9 grams of Glochidion puberum as raw medicinal materials. Wash, dry, and crush them, place them in a container, add water to cover the medicinal materials, decoct twice. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, and combine and mix the decoction liquid obtained from each decoction to obtain a combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 1200 milliliters for experimental administration to the drug-administered group in the following mouse experiment.

[0180] Mouse control experiments of the WT + H2O group and the Ki + H2O group were conducted by the method of Example 1. At the same time, 6 male and 6 female mice in the Ki + LJY-001 (high) group were added, and the mice were administered with the decoction liquid decocted from the traditional Chinese medicine composition with a high-dose ratio of the present invention. Each mouse was administered 7 milliliters of the high-dose ratio decoction liquid per day. The experiment started from the 4th week after the mice were born (the weaning time of the mice) and lasted for 27 weeks. When the mice in each group reached 30 weeks of age, 6 male and 6 female mice were respectively selected, and the intracranial calcification of the mice was observed and counted by making continuous paraffin sections of the mouse brains.

[0181] Results

[0182] Compared with the Ki + H2O group, the degree of intracranial calcification in the Ki + LJY-001 (high) group of intracranial calcification mice decreased ( Figure 2 , a-f), but the degree of decrease was not as good as that of the drug group in Example 1. For the specific method of making slices and staining, refer to Example 1.

[0183] Effect of the drug of the present invention with a low weight ratio on intracranial calcification in mice

[0184] Method

[0185] Repeat the steps of Example 1, except that the drug for preventing and treating ectopic calcification diseases used in this example is: the raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii. According to the low weight compatibility ratio of Imperata cylindrica: Coix lacryma-jobi: Glochidion puberum = 1:1:1, take 3 grams of Imperata cylindrica, 3 grams of Coix lacryma-jobi, and 3 grams of Glochidion puberum. Wash, dry, and crush them, place them in a container, add water to cover the medicinal materials, decoct twice. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, and combine and mix the decoction liquid obtained from each decoction to obtain a combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 2900 ml for experimental administration to the drug-feeding group in the following mouse experiment.

[0186] Result

[0187] Using the method of Example 1 for the mouse experiment, the degree of calcification in the drug-feeding group of mice was comparable to that of the traditional Chinese medicine group in Example 3.

[0188] Animal experiment of the drug of the present invention with a higher weight ratio in Example 5

[0189] Method

[0190] Repeat the steps of Example 1, except that the drug for preventing and treating ectopic calcification diseases used in this example is: the raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii. According to the compatibility ratio of raw medicinal materials Imperata cylindrica: Coix lacryma-jobi: Glochidion puberum = 17:54:26, take 8.5 grams of Imperata cylindrica, 27 grams of Coix lacryma-jobi, and 13 grams of Glochidion puberum. Wash, dry, and crush them, place them in a container, add water to cover the medicinal materials, decoct twice. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, and combine and mix the decoction liquid obtained from each decoction to obtain a combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 2900 ml for experimental administration to the drug-feeding group in the mouse experiment.

[0191] Result

[0192] Using the method of Example 1 for the mouse experiment, the degree of calcification in the drug-feeding group of mice was between that of Example 1 and Example 3.

[0193] Animal experiment of the drug of the present invention with a higher weight ratio in Example 6

[0194] Method

[0195] Repeat the steps of Example 1, except that the drug for preventing and treating ectopic calcification diseases used in this example is: the raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii. According to the compatibility ratio of raw medicinal materials Imperata cylindrica:Coix lacryma-jobi:Glochidion puberum = 13:39:19, take 13 grams of Imperata cylindrica, 39 grams of Coix lacryma-jobi, and 19 grams of Glochidion puberum. Wash, dry, and pulverize them, place them in a container, add water to cover the medicinal materials, decoct 2 times. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, combine and mix the decoction liquid obtained each time to obtain a combined medicinal liquid. Before the experiment, dilute this combined medicinal liquid with sterile water to 2900 milliliters for experimental administration to the medicated group in the mouse experiment.

[0196] Results

[0197] Conduct a mouse experiment by the method of Example 1. The degree of calcification of the mice in the medicated group is comparable to that in Example 5.

[0198] Animal experiment of the drug of the present invention with a higher weight ratio in Example 7

[0199] Method

[0200] Repeat the steps of Example 1, except that the drug for preventing and treating ectopic calcification diseases used in this example is: the raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii. According to the compatibility ratio of raw medicinal materials Imperata cylindrica:Coix lacryma-jobi:Glochidion puberum = 17:54:26, take 17 grams of Imperata cylindrica, 54 grams of Coix lacryma-jobi, and 26 grams of Glochidion puberum. Wash, dry, and pulverize them, place them in a container, add water to cover the medicinal materials, decoct 2 times. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, combine and mix the decoction liquid obtained each time to obtain a combined medicinal liquid. Before the experiment, dilute this combined medicinal liquid with sterile water to 2900 milliliters for experimental administration to the medicated group in the mouse experiment.

[0201] Results

[0202] Conduct a mouse experiment by the method of Example 1. The degree of calcification of the mice in the medicated group is comparable to that in Example 3.

[0203] Animal experiment of the drug of the present invention with a lower weight ratio in Example 8

[0204] Method

[0205] Repeat the steps of Example 1, except that the drug for preventing and treating ectopic calcification diseases used in this example is: the raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii Hutch. According to the compatibility ratio of the raw medicinal materials Imperata cylindrica:Coix lacryma-jobi:Glochidion puberum = 5:16:10, take 2.5 g of Imperata cylindrica, 8 g of Coix lacryma-jobi, and 5 g of Glochidion puberum. Wash, dry, and pulverize them, place them in a container, add water to cover the medicinal materials, and decoct twice. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, combine and mix the decoction liquid obtained from each decoction to obtain a combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 2900 ml for experimental administration to the medicated group in the mouse experiment.

[0206] Results

[0207] The mouse experiment was conducted in the method of Example 1, and the degree of calcification of the mice in the medicated group was comparable to that in Example 3.

[0208] Short-term animal experiment of the traditional Chinese medicine composition with the preferred weight ratio in Example 9

[0209] Method

[0210] The drug for preventing and treating ectopic calcification diseases used in this example is: the raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii Hutch. According to the compatibility ratio Imperata cylindrica:Coix lacryma-jobi:Glochidion puberum = 16:55:27, take 4 g of Imperata cylindrica, 13.75 g of Coix lacryma-jobi, and 6.75 g of Glochidion puberum. Wash, dry, and pulverize them, place them in a container, add water to cover the medicinal materials, and decoct twice. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, combine and mix the decoction liquid obtained from each decoction to obtain a combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 2900 ml for experimental administration to the medicated group in the following mouse experiment.

[0211] A control experiment of mice in the Ki+H2O group at 30 weeks of age was conducted in the method of Example 1. At the same time, 5 male mice in the Ki+H2O group at 21.5 weeks of age and 5 male mice in the Ki+LJY-001 group at 30 weeks of age (administering drugs to mice between 21.5 weeks and 30 weeks of age) were added. The medicinal liquid decocted from the traditional Chinese medicine composition with the preferred weight ratio of the present invention was used for administration, and each mouse was given 7 ml of the high-dose ratio medicinal liquid every day. The experiment started at 21.5 weeks of age after the mice were born and lasted for 8.5 weeks. When the mice in each group reached 21.5 weeks, 30 weeks, and 30 weeks of age respectively, 5 male mice were taken from each group, and the intracranial calcification of the mice was observed and counted by making continuous paraffin sections of the mouse brains.

[0212] Results

[0213] Compared with the Ki+H2O (30 weeks) group at 30 weeks of age, the degree of intracranial calcification in mice with intracranial calcification in the Ki+LJY-001 (21.5-30 weeks) group at 30 weeks of age (medication was administered to mice between 21.5 weeks and 30 weeks of age) was reduced ( Figure 4 , a-d). For the specific method of section preparation and staining, refer to Example 1.

[0214] Example 10 Animal experiments of the drug of the present invention prepared from two raw medicinal materials, Coix lacryma-jobi and Glochidion puberum

[0215] Method

[0216] The drug for preventing and treating ectopic calcification diseases used in this example is: The raw medicinal materials Coix lacryma-jobi and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion puberum Hance. According to the compatibility ratio of raw medicinal materials Coix lacryma-jobi:Glochidion puberum = 278:139, take 27.8 grams of Coix lacryma-jobi and 13.9 grams of Glochidion puberum, wash, dry, and pulverize them, place them in a container, add water to cover the medicinal materials, decoct twice, the first decoction for 60 minutes, the second decoction for 30 minutes, filter the decoction, combine and mix the decoction obtained each time to obtain the combined decoction. Before the experiment, dilute the combined decoction with sterile water to 1200 ml for experimental administration to the medicated group in the following mouse experiments. Conduct mouse experiments in the method of Example 1, and the degree of calcification in the Chinese medicine group of mice is equivalent to that in the Chinese medicine group in Example 2. The specific data is as follows:

[0217] Carry out mouse control experiments on the WT+H2O group and the Ki+H2O group in the method of Example 1. At the same time, add 6 male and 6 female mice in the Ki+LJY-001 (BC) group, and administer the decoction prepared from the Chinese medicine composition with the dosage ratio of the two medicinal materials Imperata cylindrica and Coix lacryma-jobi of the present invention. Each mouse takes 7 ml of the decoction every day. The experiment starts from the 4th week after the mice are born (the weaning time of the mice) and lasts for 27 weeks. When the mice in each group reach 30 weeks of age, 6 male and 6 female mice are taken respectively, and the intracranial calcification of the mice is observed and counted by making continuous paraffin sections of the mouse brain.

[0218] Results

[0219] Compared with the Ki+H2O group, the degree of intracranial calcification in mice with intracranial calcification in the Ki+LJY-001 (BC) group was reduced ( Figure 5 c), but the degree of reduction is not as good as that in the drug group of Example 1. For the specific method of section preparation and staining, refer to Example 1.

[0220] Example 11 Animal experiments of the drug of the present invention prepared from two raw medicinal materials, Imperata cylindrica and Glochidion puberum

[0221] Method

[0222] The drug for preventing and treating ectopic calcification diseases used in this embodiment is as follows: the raw medicinal materials Imperata cylindrica and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii Hutch. According to the compatibility ratio of the raw medicinal materials Imperata cylindrica:Glochidion puberum = 83:139, take 8.3 grams of Imperata cylindrica and 13.9 grams of Glochidion puberum, wash, dry, and pulverize them, place them in a container, add water to cover the medicinal materials, decoct twice. The first decoction is for 60 minutes, and the second decoction is for 30 minutes. Filter the decoction liquid, combine and mix the decoction liquid obtained from each decoction to obtain a combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 1200 ml for experimental administration to the medicated group in the following mouse experiment. Conduct the mouse experiment by the method of Example 5. The degree of calcification of the mice in the traditional Chinese medicine group is comparable to that of the traditional Chinese medicine group in Example 2.

[0223] The specific data is as follows:

[0224] Conduct the mouse control experiments for the WT+H2O group and the Ki+H2O group by the method of Example 1. At the same time, add 6 male and 6 female mice in the Ki+LJY-001(AC) group, and administer the decoction liquid prepared from the traditional Chinese medicine composition with the dosage ratio of the two medicinal materials Imperata cylindrica and Glochidion puberum of the present invention. Each mouse takes 7 ml of the decoction liquid every day. The experiment starts from the 4th week after the mice are born (the weaning time of the mice) and lasts for 27 weeks. When the mice in each group reach 30 weeks of age, 6 male and 6 female mice are taken respectively. By making continuous paraffin sections of the mouse brains, observe and count the intracranial calcification conditions of the mice.

[0225] The results are as Figure 5 , as shown in a-f.

[0226] Compared with the Ki+H2O group, the degree of intracranial calcification of the mice with intracranial calcification in the Ki+LJY-001(AC) group is reduced ( Figure 5 d), but the reduction degree is not as good as that of the drug group in Example 1. The specific methods for making sections and staining refer to Example 1.

[0227] Animal experiment of the drug of the present invention prepared from the two medicinal materials Imperata cylindrica and Coix lacryma-jobi in Example 12

[0228] Method

[0229] The drug for preventing and treating ectopic calcification diseases used in this embodiment is: the raw medicinal materials Imperata cylindrica and Coix lacryma-jobi are the dried roots of the corresponding medicinal materials. According to the ratio of the raw medicinal materials compatibility Imperata cylindrica:Coix lacryma-jobi = 83:278, 8.3 grams of Imperata cylindrica and 27.8 grams of Coix lacryma-jobi are taken, washed, dried, and pulverized, placed in a container, added with water to cover the medicinal materials, decocted twice, the first decoction for 60 minutes, the second decoction for 30 minutes, the decoction liquid is filtered, and the decoction liquids obtained from each decoction are combined and mixed to obtain a combined decoction liquid. Before the experiment, the combined decoction liquid is diluted with sterile water to 1200 ml for experimental administration to the medicated group in the mouse experiment. The mouse experiment is carried out by the method of Example 1, and the degree of calcification of the mice in the traditional Chinese medicine group is equivalent to that of the traditional Chinese medicine group in Example 2. The specific data is as follows:

[0230] The mouse control experiments of the WT+H2O group and the Ki+H2O group were carried out by the method of Example 1. At the same time, 6 male and 6 female mice in the Ki+LJY-001(AB) group were added, and the mice were administered with the decoction liquid decocted from the traditional Chinese medicine composition with the dosage ratio of the two medicinal materials Imperata cylindrica and Coix lacryma-jobi of the present invention, and each mouse was given 7 ml of the decoction liquid every day. The experiment started from the 4th week after the mice were born (the weaning time of the mice) and lasted for 27 weeks. When the mice in each group reached 30 weeks of age, 6 male and 6 female mice were taken respectively, and the intracranial calcification of the mice was observed and counted by making continuous paraffin sections of the mouse brain.

[0231] Method

[0232] Compared with the Ki+H2O group, the degree of intracranial calcification of the mice with intracranial calcification in the Ki+LJY-001(AB) group was slightly reduced ( Figure 5 e). The specific method for making sections and staining refers to Example 1.

[0233] Animal experiment of the drug of the present invention prepared from the single medicinal material Imperata cylindrica in Example 13

[0234] Method

[0235] Repeat the steps of Example 1, except that the drug for preventing and treating ectopic calcification diseases used in this embodiment is: taking Imperata cylindrica as the raw medicinal material, taking 8.3 grams of Imperata cylindrica, washing, drying, and pulverizing, placing in a container, adding water to cover the medicinal materials, decocted twice, the first decoction for 60 minutes, the second decoction for 30 minutes, the decoction liquid is filtered, and the decoction liquids obtained from each decoction are combined and mixed to obtain a combined decoction liquid. Before the experiment, the combined decoction liquid is diluted with sterile water to 2900 ml for experimental administration to the medicated group in the mouse experiment.

[0236] Result

[0237] The mouse experiment was carried out by the method of Example 1, and there was no significant difference in the degree of calcification between the medicated group and the water-fed group.

[0238] Animal experiment of the drug of the present invention prepared from the single medicinal material Coix lacryma-jobi in Example 14

[0239] Method

[0240] The drug for preventing and treating ectopic calcification diseases used in this example is: the raw material medicinal material Coix lacryma-jobi is the dried root of the corresponding medicinal material. Take 27.8 grams of Coix lacryma-jobi, wash, dry in the sun, pulverize, place in a container, add water to cover the medicinal material, decoct 2 times, the first decoction for 60 minutes, the second decoction for 30 minutes, filter to obtain the decoction liquid, combine and mix the decoction liquid obtained each time to obtain the combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 2900 ml for experimental administration to the drug-feeding group in the mouse experiment.

[0241] Results

[0242] Using the method of Example 1 for the mouse experiment, there was no significant difference in the degree of calcification between the drug-feeding group and the water-feeding group of mice.

[0243] Animal experiment of the drug of the present invention prepared from the single medicinal material Glochidion puberum in Example 15

[0244] Method

[0245] The drug for preventing and treating ectopic calcification diseases used in this example is: the raw material medicinal material Glochidion puberum is the dried root of the corresponding medicinal material. Glochidion puberum is specifically Glochidion wilsonii Hutch. Take 13.9 grams of Glochidion puberum, wash, dry in the sun, pulverize, place in a container, add water to cover the medicinal material, decoct 2 times, the first decoction for 60 minutes, the second decoction for 30 minutes, filter to obtain the decoction liquid, combine and mix the decoction liquid obtained each time to obtain the combined decoction liquid. Before the experiment, dilute this combined decoction liquid with sterile water to 2900 ml for experimental administration to the drug-feeding group in the mouse experiment.

[0246] Results

[0247] Using the method of Example 1 for the mouse experiment, there was no significant difference in the degree of calcification between the drug-feeding group and the water-feeding group of mice.

[0248] Calcium deposition in patients with intracranial calcification treated with the drug of the present invention in Example 16

[0249] Method

[0250] The drug for preventing and treating ectopic calcification used in this example is: the raw material medicinal materials Imperata cylindrica, Coix lacryma-jobi and Glochidion puberum are the dried roots of the corresponding medicinal materials. Glochidion puberum is specifically Glochidion wilsonii Hutch. Take 8 grams of Imperata cylindrica, 12 grams of Coix lacryma-jobi, and 10 grams of Glochidion puberum, wash, dry in the sun, pulverize, place in a container, add water to cover the medicinal material, soak for 1 hour, decoct 3 times, the first decoction for 60 minutes, the second and third decoctions for 30 minutes each, filter to obtain the decoction liquid, combine and mix the decoction liquid obtained each time to obtain the combined liquid, which is used as the dosage of one unit.

[0251] The patient (Luo, female, 54 years old) showed symptoms of heaviness on the top of the head. Mild intracranial calcification was found by brain CT examination. At the age of 54, she started taking medicine, taking 1 unit of the dosage per day, divided into three times, once in the morning, once at noon, and once in the evening, for a duration of 14 days.

[0252] Results

[0253] After 14 days of continuous medication, it was found that the symptoms of heaviness on the top of the head were relieved, and the mild calcified nodules in the brain disappeared by brain CT examination.

[0254] Example 17 Calcium deposition in patients with intracranial calcification treated with the drug of the present invention

[0255] Method

[0256] The drug used to prevent and treat ectopic calcification in this example is: the raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii Hutch. Take 2 grams of Imperata cylindrica, 8 grams of Coix lacryma-jobi, and 6 grams of Glochidion puberum, wash, dry, and pulverize them, place them in a container, add water to cover the medicinal materials, soak for 1 hour, and decoct 3 times. The first decoction is for 60 minutes, and the second and third decoctions are each for 30 minutes. Filter the decoction liquid, and combine and mix the decoction liquid obtained from each decoction to obtain a combined liquid, which is used as one unit of the dosage.

[0257] The patient (Liu, male, 12 years old, weight about 42 kg) showed symptoms of epileptic seizures, movement disorders, and intellectual abnormalities from time to time. Obvious intracranial calcification was found by brain CT examination ( Figure 6 ), and at the age of 12, he started taking medicine, taking 1 unit of the dosage per day, divided into three times, once in the morning, once at noon, and once in the evening, for a duration of 1 month.

[0258] Results

[0259] After 1 month of continuous medication, it was found that the frequency of epileptic seizures decreased; the movement disorder was relieved, and walking began to return to normal; the thinking became clearer; no brain CT reexamination was performed.

[0260] Example 18 Calcium deposition in patients with kidney stones treated with the drug of the present invention

[0261] Method

[0262] The drug used for preventing and treating ectopic calcification in this embodiment is as follows: The raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii. Take 8 grams of Imperata cylindrica, 12 grams of Coix lacryma-jobi, and 10 grams of Glochidion puberum, wash, dry, and pulverize them. Place them in a container, add water to cover the medicinal materials, soak for 1 hour, and decoct 3 times. The first decoction is for 60 minutes, and the second and third decoctions are each for 30 minutes. Filter the decoction, and combine and mix the decoctions obtained each time to obtain a combined liquid, which is used as the dosage of one unit. The patient (Mr. Xia, 54 years old) showed unbearable pain, and obvious calcium deposition was detected in the kidneys by type B ultrasound; in previous treatments, after taking the lithagogue, symptoms such as hematuria and pain occurred and recurred every year. At the age of 54, he started taking the medicine for the first time, taking 1 unit dosage per day, divided into three times, once in the morning, once at noon, and once in the evening, for 14 consecutive days. After several months, he started taking the medicine for the second time, taking 1 unit dosage per day, divided into three times, once in the morning, once at noon, and once in the evening, for 2 rounds, with each round lasting for 7 days.

[0263] Results

[0264] After the first dose, the pain disappeared, and the stones were discharged painlessly. Type B ultrasound examination found that the left kidney stones disappeared, and there were still a small number of stones in the right kidney. During the second dose, the stones were discharged painlessly again. After the medicine-taking ended, type B ultrasound examination found that the right kidney stones also disappeared, and there has been no recurrence so far.

[0265] Example 19 Treatment of calcium deposition in kidney stone patients with the drug of the present invention

[0266] Method

[0267] The drug used for preventing and treating ectopic calcification in this embodiment is as follows: The raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii. Take 8 grams of Imperata cylindrica, 12 grams of Coix lacryma-jobi, and 10 grams of Glochidion puberum, wash, dry, and pulverize them. Place them in a container, add water to cover the medicinal materials, soak for 1 hour, and decoct 3 times. The first decoction is for 60 minutes, and the second and third decoctions are each for 30 minutes. Filter the decoction, and combine and mix the decoctions obtained each time to obtain a combined liquid, which is used as the dosage of one unit. The patient (Mr. Xiong, 37 years old) showed pain in the left kidney, and obvious kidney stones were detected in the left kidney by type B ultrasound. At the age of 37, he started taking the medicine, taking 1 unit dosage per day, divided into three times, once in the morning, once at noon, and once in the evening, for 7 consecutive days.

[0268] Results

[0269] The pain was relieved, and type B ultrasound examination found that the left kidney stones disappeared, and there has been no recurrence so far.

[0270] Example 20 Treatment of calcium deposition in patients with eye stones with the drug of the present invention

[0271] Method

[0272] The drug used in this embodiment for preventing and treating ectopic calcification is: the raw medicinal materials Imperatae cylindrica, Coix lachryma-jobi and Abacus palpebratae are the dried roots of the corresponding medicinal materials, and Abacus palpebratae is specifically Hubei Abacus palpebratae. Take 8 grams of Imperatae cylindricae, 12 grams of Coix lachryma-jobi and 10 grams of Abacus palpebratae, wash, dry, crush, place in a container, add water to cover the medicinal materials, soak for 1 hour, decoct 3 times, decoct for 60 minutes for the first time, decoct for 30 minutes for the second and third times, filter the decoction, combine and mix the decoction obtained from each decoction to obtain a combined liquid, as a unit of drug dosage. The patient (Liu, female, 54 years old) has multiple white spot-like lumps on the conjunctiva of the eyelid, showing obvious foreign body sensation. She started taking the medicine at the age of 54, taking 1 unit of drug dosage per day, divided into three doses, once in the morning, noon and evening, for a duration of 14 days.

[0273] result

[0274] During the medication period, granular white hard particles were discharged from the corners of the eyes, and the white spot-like lumps on the conjunctiva of the palpebral conjunctiva decreased. The collected white hard particles were stained for calcification-specific staining - Alizarin red staining, and the result was positive.

[0275] Example 21: Treatment of calcification of scapulohumeral periarthritis with the drug of the present invention

[0276] method

[0277] The drug used in this embodiment for preventing and treating ectopic calcification is: the raw medicinal materials Imperatae cylindrica, Coix lachryma-jobi and Abacus palustris are the dried roots of the corresponding medicinal materials, Abacus palustris is specifically Hubei Abacus palustris, 8 grams of Imperatae cylindrica, 12 grams of Coix lachryma-jobi and 10 grams of Abacus palustris are taken, washed, dried, crushed, placed in a container, water is added to cover the medicinal materials, soaked for 1 hour, decocted 3 times, the first decoction was 60 minutes, the second and third decoctions were 30 minutes each, the decoction was filtered, and the decoction obtained by each decoction was combined and mixed to obtain a combined liquid as a unit of dosage. A patient with calcification of scapulohumeral periarthritis (Luo, male, 55 years old) showed shoulder pain and limited arm movement. He started taking medicine at the age of 55, taking 1 unit of dosage per day, divided into three doses, once in the morning, noon and evening, for a duration of 14 days.

[0278] result

[0279] After taking the medicine, I felt that the shoulder pain was obviously relieved and the shoulder joint movement was restored.

[0280] Example 22: Treatment of bladder and prostate calcification with the drug of the present invention

[0281] method

[0282] The drug used in this embodiment for preventing and treating ectopic calcification is as follows: The raw medicinal materials Imperata cylindrica, Coix lacryma-jobi, and Glochidion puberum are the dried roots of the corresponding medicinal materials. Specifically, Glochidion puberum is Glochidion wilsonii. Take 4 grams of Imperata cylindrica, 13 grams of Coix lacryma-jobi, and 8 grams of Glochidion wilsonii. Wash, dry, and pulverize them, place them in a container, add water to cover the medicinal materials, soak for 1 hour, and decoct 3 times. The first decoction is for 60 minutes, and the second and third decoctions are each for 30 minutes. Filter the decoction, and combine and mix the decoctions obtained each time to obtain a combined liquid, which is used as the dosage of one unit. A patient with bladder and prostate calcification (Mr. Xiong, male, 77 years old) showed frequent urination and urgency, especially severe at night, with a urination frequency of once per hour, dripping urine during urination, and accompanied by lower limb edema; imaging examination showed that the bladder wall was slightly thick, with a nodular dense shadow about 2.4 cm long inside, the prostate was enlarged, and patchy calcification foci were seen inside. At the age of 77, he started taking the medicine, taking 1 unit dosage per day, divided into three times, once in the morning, once at noon, and once in the evening, for a duration of 28 days.

[0283] Results

[0284] After taking the medicine, the phenomenon of frequent urination and urgency was significantly improved. There was no more urgency during the day, the urination frequency at night decreased to once every 3 - 4 hours, there was no more dripping urine, the overall complexion of the patient improved, and no side effects were seen.

[0285] Discussion

[0286] Before 2012, its pathogenic mechanism was unknown. We started from the family tree and cloned the first pathogenic gene SLC20A2 of IBGC through genetic analysis for the first time. Functional analysis found that this gene mutation affects the cell's transport of inorganic phosphorus, resulting in the accumulation of inorganic phosphorus (Pi) in the extracellular matrix and causing the disease. Currently, studies have found that about 50% of IBGC patients are caused by mutations in the SLC20A2 gene. We constructed mice with the slc20a2 gene mutation (p.S602W), and after identification, these mice showed obvious intracranial calcification phenotypes; therefore, the slc20a2 gene mutation (p.S602W) mice are good intracranial calcification model mice and can be used for the research and development of drugs for treating intracranial calcification. The drug provided by the present invention has an obvious inhibitory effect on the occurrence and development of intracranial calcification in intracranial calcification model mice, which is of great significance for further developing drugs for treating intracranial calcification diseases.

[0287] In the embodiment of the present invention, by administering the drug compositions of the present invention with different compatibilities to the model mice, the effects of treating intracranial calcification diseases are evaluated. By adjusting the compatibility of the present invention, it is found that when the drug composition of the present invention contains the following components and compatibilities, it can effectively treat intracranial calcification diseases:

[0288] When the active ingredients are A, B, and C, the compatibility ratio of A, B, and C is A:B:C = (1 - 84):(1 - 278):(1 - 140), preferably A:B:C = (1 - 15):(1 - 40):(1 - 20).

[0289] When the active ingredients are A and B, their compatibility ratio is: A:B = (1 - 84):(1 - 278), preferably: A:B = 83:278.

[0290] When the active ingredients are A and C, their compatibility ratio is: A:C = (1 - 84):(1 - 140), preferably: A:C = 83:139.

[0291] When the active ingredients are B and C, their compatibility ratio is: B:C = (1 - 278):(1 - 140), preferably: B:C = 278:139.

[0292] All documents mentioned in the present invention are incorporated herein by reference as if each document was individually incorporated by reference. In addition, it should be understood that after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims

1. A pharmaceutical composition, characterized in that, Comprising two or three medicinal materials selected from the group consisting of active ingredient A, active ingredient B, or active ingredient C, wherein active ingredient A is selected from the group consisting of the roots of Imperata cylindrica Beauv. or its extract; active ingredient B is selected from the group consisting of the seeds, roots of Coix lacryma-jobi L. or its extract; active ingredient C is selected from the dried roots, leaves, fruits of any plant of the genus Glochidion or its extract.

2. The pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition contains active ingredients A, B, and C; wherein the compatibility ratio of active ingredients A, B, and C is A:B:C = (1 - 84):(1 - 278):(1 - 140), preferably A:B:C = (1 - 15):(1 - 40):(1 - 20).

3. The pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition contains two medicinal materials selected from active ingredient A, active ingredient B, and active ingredient C; wherein when the pharmaceutical composition contains active ingredients A and B, the compatibility ratio is: A:B = (1 - 84):(1 - 278), preferably: A:B = 83:278; wherein when the pharmaceutical composition contains active ingredients A and C, the compatibility ratio is: A:C = (1 - 84):(1 - 140), preferably: A:C = 83:139; wherein when the pharmaceutical composition contains active ingredients B and C, the compatibility ratio is: B:C = (1 - 278):(1 - 140), preferably: B:C = 278:

139.

4. Use of a pharmaceutical composition according to any one of claims 1 to 3 or a preparation containing the pharmaceutical composition, characterized in that, The pharmaceutical composition or preparation is used for preparing a drug for preventing and / or treating and / or alleviating ectopic calcification diseases and their related complications.

5. The use according to claim 4, characterized in that, The drug is also used for inhibiting calcification deposition.

6. The use according to claim 4, characterized in that, The ectopic calcification diseases are selected from the group consisting of intracranial calcification, kidney stones, eye stones, calcification of scapulohumeral periarthritis, bladder calcification, prostate calcification, or a combination thereof; the complications of the intracranial calcification diseases are selected from the group consisting of Parkinson-like symptoms, ataxia, dystonia, dementia, memory decline, mental confusion, emotional disorder, epilepsy, migraine, or a combination thereof.

7. Use of a pharmaceutical composition according to any one of claims 1 to 3 or a preparation containing the pharmaceutical composition, characterized in that, The pharmaceutical composition or preparation is used for preparing a drug for preventing and / or treating and / or alleviating intracranial calcification diseases.

8. The use according to claim 7, characterized in that, The drug is also used for inhibiting intracranial calcification deposition.

9. A method for preparing the pharmaceutical composition according to claim 1, characterized in that, Including the steps: (1) Providing a first mixture of any two or three selected from active ingredients A, B, and C, and decocting with water; (2) Obtaining the decoction, and the obtained decoction is the pharmaceutical composition.

10. The method according to claim 9, characterized in that, Before the step (1), there is also a step of taking the roots of any two or three selected from raw medicinal materials A, B, or C, washing, drying in the sun, pulverizing, and mixing to obtain a first mixture.

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