CN104147073A - Traditional Chinese medicine preparation formula capable of warming kidney and invigorating yang as well as preventing and treating osteoporosis, production technology and application thereof - Google Patents

Abstract

The invention relates to a traditional Chinese medicine preparation formula capable of warming kidney and invigorating yang as well as preventing and treating osteoporosis, a production technology and an application thereof, which belongs to the technical field of traditional Chinese medicine production and clinic medical field. The researches found that a traditional Chinese medicine compound preparation composed of epimeddium, pearl layer powder and common cnidium fruit is capable of warming kidney and invigorating yang, and has good prevention and treatment effects for treating osteoporosis. The preparation is authorized by local drug administration department, and can be taken as a hospital preparation for clinic application according to a doctor prescription, through 20 years application, the preparation has the advantages of warming kidney and invigorating yang, strengthening muscles and bones, dispelling rheumatism, and preventing osteoporosis, and can be used for impotence spermatorrhea, soft muscles and bones, rheumatism and impediment pain, tendon spasm, cold in uterus, cold-damp morbid leucorrhea and the like. The traditional Chinese medicine preparation formula has obvious curative effect on various osteoporosis and has no adverse reaction.

Description

Warming the kidney to invigorate YANG is prevented and treated formula, production technology and the application thereof of osteoporotic Chinese medicine preparation

Technical field is a kind of to be had warming the kidney to invigorate YANG and prevents and treats the formula of osteoporotic Chinese medicine preparation, production technology and application thereof, belongs to production technical field and the clinical treatment field of Chinese medicine.

Background technology osteoporosis is a health problem worldwide, that more and more attract people's attention.The whole world approximately 200,000,000 people suffer from osteoporosis at present, and its sickness rate has leapt to commonly encountered diseases, frequently-occurring disease the 7th.Estimate that ill total number of persons has exceeded 200,000,000.Osteoporosis is the modal disease of old people.In the U.S. and western countries, exceed in 55 years old postclimacteric women at the age, there is the people of half to suffer from the osteoporosis that degree is different, and in the old people of over-65s, suffer from osteoporosis person up to more than 95%.Along with the reach of science and the mankind's progress, the average life span constantly extends, and aging population increase sharply, and osteoporotic sickness rate is also along with occurring increase rapidly.Estimate to the year two thousand fifty whole world over-65s old people will be increased to 15.55 hundred million by current 3.23 hundred million, osteoporosis causes hip fracture generation number also will to be increased to 6,260,000 by current 1,660,000 when the time comes, and wherein the patient of Asia, Latin America, the Middle East and African country will account for more than 70%.According to official statistics, the U.S. reaches 10,000,000,000 dollars for the direct and indirect cost of osteoporosis aspect every year; The fund that the health of Britain and social security institution provide for osteoporosis every year exceedes 500,000,000 pounds; France only pays the patient's of 30,000 fracture of femoral neck hospitalization cost approximately 13.5 hundred million French Francs every year on average.Like this huge society and financial burden that osteoporosis causes, formed a serious global problem, caused the very big concern of countries in the world.The arrival of aging society is increased osteoporotic incidence rate increasingly, serious threat people's quality of life.

China is the country that world population is maximum, wherein aging population account for Asia aging population 1/2 and world population 1/5.The osteoporosis Epidemiological study result in Beijing, Shanghai and 3 cities, Chengdu shows, 60-69 year osteoporotic incidence rate women of age bracket and male are respectively 60% and 30% left and right.China's large population base, sufferers of osteoporosis face has reached 6,000 ten thousand～8,000 ten thousand examples, and this brings serious burden to family and society.People according to another statistics national over-65s in 2000 has 1.3 hundred million, accounts for 10.7% of national population, has become typical veteran form country.And the patient who suffers from osteoporosis accounts for 90% in these crowds, and the patient of hip fracture will have 12%～40% to die from various complication in 1 year.In survivor, also there is 50% human action inconvenience.This has not only caused serious body and mind to wreck to patient, has increased huge manpower and financial resources burden also to family and society simultaneously.Therefore, preventing and treating osteoporosis is defying age, life-saving, the very urgent research topic of the guarantee people's quality of life.

At present both at home and abroad very limited, the conventional bone mineralising promoter of Prevention and Treatment of Osteoporosis medicine is as limited in calcium preparation, vitamin D curative effect; Though bone resorption inhibitor has certain effect as estrogen, calcitonin, diphosphate, ipriflavone etc., untoward reaction is also many, affects clinical practice, and bone formation-promoter is disputed on as the curative effect of fluoride always, and the U.S. does not also go on the market so far.Aspect clinical treatment, from controversies in hormone replacement in the elderly, to diphosphonic acid salt, the control of the medicines such as calcitonin several important developmental stage of having passed by, just proceeding at present the treatment research to cytokines such as bone morphogenic protein-2 Pseudobulbus Bletillae (Rhizoma Bletillae) interleukin, but, to so far, these,, for preventing and treating osteoporotic medicine, all have many side effect, and some curative effect is general, some is expensive, at present still there is no a kind of generally acknowledged ideal medicament, therefore, searching high-efficiency low-toxicity is prevented and treated osteoporotic medicine and is remained the task that pharmacology worker is urgent.Osteoporosis and anti-aging be the hot subject of at present both at home and abroad medical circle research, along with the arrival of at present internal and international upper senescence society, the world is being faced with the aged and is being on the increase, population is the aging epoch constantly, for this reason, research has control senile osteoporosis and antidotal new drug, has become the key subjects that medical worker faces.

Herba Epimedii, claims again Herba Epimedii, is the Chinese medicine that tcm clinical practice is conventional, has kidney invigorating and YANG supporting, expelling wind and removing dampness.Control sexual impotence erectile problem, hemiplegia is unsuccessful, dribbling urination, and muscles and bones contraction is anxious, cough, optic atrohic blindness after being ill, toothache caused by fire of deficiency type, hemiplegia, weakness of the waist and knees, rheumatic arthralgia, extremity are meciless.Also there is document to record, cure mainly impotence and premature ejaculation, pain in the low back and legs, numb limbs and tense tendons, hemiplegia, neurasthenia, forgetful, tinnitus, dizzy disease such as grade.Osteoporosis is called " atrophic debility of bones " and " rheumatism involving the bone " traditional Chinese medical science angle, and the traditional Chinese medical science is thought " marrow bone growth promoting, therefore the institute of bone person kidney closes also, smart sufficient marrow foot, marrow is in bone, marrow is sufficient, and bone is strong for kidney storing essence, the raw marrow of essence ".In recent years, many scholars, according to the theory of " kidney storing essence, the raw marrow of main bone ", are studied with the relation of bone density and osseous tissue content suffering from a deficiency of the kidney, illustrating the reduction of suffering from a deficiency of the kidney with bone density or osseous tissue content has significant correlation, and these results of study are consistent with the traditional Chinese medical science " kidney governing bones " theory.Modern pharmacology research shows, Herba Epimedii has panimmunity and regulates, affect the pharmacologically actives such as endocrine, especially its anti-sclerotin pine dredge act on very outstanding.Prevent and treat osteoporotic effect about Herba Epimedii, existing bibliographical information, Herba Epimedii water extract can significantly improve the Serum alkaline phosphatase activity of ovariectomized female rats, the concentration of rising Determination of Calcium in Serum, promoting bone growing, increase cortical bone and bone trabecula quantity, have the effect that significantly prevents bone loss and osteoporosis; The main component icariin of Herba Epimedii can significantly promote proliferation of rat osteoblasts, and strengthens its osteogenic activity.Herba Epimedii extracting solution can prevent the osteoporosis rat of glucocorticoid inducible, can promote osteoclast formation and strengthen its activity by lowering OPG/RANKL ratio, promotes that osseous tissue absorbs the glucocorticoid-induced osteoporosis and the femur head necrosis that cause; Herba Epimedii extracting solution whole body osteoporosis and the loose bone resorption process of jawbone that removal ovary rabbit causes due to estrogenic reduction that can slow down, prompting Herba Epimedii energy selectivity suppresses the absorption at the damaged place of osteoporotic bone.Research shows, the main effective ingredient of Herba Epimedii function of resisting osteoporosis is Flavonoid substances, wherein, affect bone metabolism activity with icariin again the strongest, its mechanism of action mainly plays a role by following approach: 1. improve the gene expression of osteoprotegerin (OPG), thus the propagation of stimulating osteoblast and differentiation promoting bone growing; 2. increase and transform the generation that generates the factor and the expression that reduces tumor necrosis factor, and then stop the generation of osteoclast in bone marrow matrix to prevent bone loss, reach the object that prevention of osteoporosis occurs; 3. regulate and control the balance of osteoblast/osteoclast activity; 4. reduce Ca in osteoclast ²⁺concentration, reduces ultra-oxygen anion free radical in the contracting of actin loopback and cell, causes osteoblast absorption lacuna area to reduce.Bone resorption amount reduces.Except above-mentioned mechanism of action,

Herba Epimedii is now widely used in the control of senile osteoporosis clinically, clinical observation is found, add and can improve insulin and the osteoporotic curative effect of calcium treatment diabetes with Herba Epimedii, patient's pain relief rate, pain time obviously shorten, bone density significantly raises, and Herba Epimedii and insulin combination application can be brought into play synergism.The Chinese medicine compound Psoralen capsule being made up of Herba Epimedii, Fructus Psoraleae etc. can prevent bone loss effectively, and can make mineralising sclerotin content obviously increase. clinical trial patient even can return to and approach normal bone level of density.The symptoms such as patient's lumbago and backache, myalgia, arthralgia can obviously be improved or cure to the BUSHEN JIANGU JIAONANG that is Herba Epimedii by main component after 3 months, to 27 routine osteoporosis case treatments, and bone density increases to some extent, and in rising trend.In addition, the close osteocomma that formed by Herba Epimedii etc., protect bone mixture etc. to finding in the clinical effect trial of postmenopausal osteoporosis: close osteocomma can make the symptoms such as patient's whole body osteodynia and aching pain in waist and back and sign obviously improve, therapeutic effect is obviously better than nilestriol matched group, its chi, radius bone mineral content are treated front obvious increase, obviously reduce calcium/urine creatine on an empty stomach.What other were applied clinically fills out marrow soup, kidney tonifying, essence replenishing side etc. and loses suppressing bone, improves osteoporosis symptom and all obtained good therapeutic effect as returned bone ball, two celestial kidney qi soup, kidney tonifying containing medicines of Herba Epimedii.

Margarita layer powder is Margarita inwall grinds, with Margarita powder be homology, contained composition is identical with Margarita, is mainly calcium, several amino acids and a small amount of trace element, wherein contained angle glutelin has the unit aminoacid that human body can not be synthetic.Skin care that Margarita, Margarita layer powder have, tranquillizing and allaying excitement, tomorrow removing nebula, dispel the effects such as liver-fire, removing toxic substances and promoting granulation, treatment ulcer, all on the books in China's successive dynasties medical book, the health-care effect of Margarita layer powder is: acne removing, speckle removing, brighten, skin care; Medicinal efficacy is: suppressing the hyperactive liver arresting convulsion, tranquilizing mind, heat-clearing and toxic substances removing.Modern pharmacological research report, Margarita layer powder can significantly improve the activity of GSH-Px in whole blood, significantly reduces the content of serum lipid peroxide, also can significantly reduce liver lipofuscin content, also very remarkable to the reduction of heart lipofuscin, point out Margarita layer powder to there is certain antioxidation.Report that in addition Margarita layer powder can obviously extend average life and the maximum life span of fruit bat, can extend the swimming time of white mice, have the ashamed use of certain resisting fatigue.Nacreous layer part can also obviously increase castration rat preputial glands, the prostatic weight of seminal vesicle. and showing has androgen-like action, can increase the weight of immaturity male white mouse testis, and sperm quantity and motility of sperm are had no significant effect.Can increase the adrenal weight of immaturity male white mouse, radiation-induced white mice hemopoietic function damage is had to certain protective role. improve lethal dose radiation damage white mice survival rate and mean survival time.

Fructus Cnidii is the dry mature fruit of samphire cnidium monnieri, and summer, two season of autumn gather when fruit maturation, remove impurity, dry.Begin to be loaded in Shennong's Herbal, acrid in the mouth, hardship, warm in nature, enter kidney, spleen channel, tool dispels the wind, the function of dampness, parasite killing, antipruritic and warming the kidney to activate YANG.The function that separately has document to record Fructus Cnidii cures mainly: warming the kidney to invigorate YANG, dampness, dispels the wind, parasite killing.For sexual impotence, cold womb, cold-damp leukorrhagia, arthralgia chiefly caused by damp pathogen lumbago; External treatment vulval eczema, married woman's pudendal pruritus, trichomonal vaginitis.This project team finds that Fructus Cnidii has obvious function of resisting osteoporosis to ovariectomized female rats, domestic other scholars have also proved the different from estradiol of osteoporosis that Fructus Cnidii causes castrated rats subsequently, in castrated rats urine, deoxypyridinoline increases, but in serum, BGP content does not change.Research also finds that Fructus Cnidii can improve the activity of castrated rats androgen, promoting sexual gland hormone content and nitricoxide synthase, and prompting osthole has androgen-like action and the effect of promoting sexual gland hormone sample.Fructus Cnidii can improve femur of mature ovariectomized rats bone density, does not cause endometrial hyperplasia, can be considered as selective estrogen receptor modulators application.Isolated experiment shows Fructus Cnidii energy stimulating osteoblast thymus pyrimidine and proline incorporation, points out its propagation with stimulation in rats osteocyte and ossein anabolic effect; In the time that osteoblast alkaline phosphatase activities is the highest, Fructus Cnidii significantly increases the activity of osteoblast alkali phosphatase, and this effect is its effect basis that increases bone amount.In addition, Fructus Cnidii can be suppressed to osteocyte spontaneously or produce NO, IL-1 and IL-6 under inflammatory cytokine and LPS stimulation, reduce the level of NO, IL-1 and IL-6, part regulates osteoblastic function, reduce the stimulation to the differentiation of osteoclast precursor Growth of Cells, reduce the number of osteoclast and the bone resorption of broken bone, thereby reduced the loss of sclerotin.Have research also to find, Fructus Cnidii can promote osteoblastic proliferation and differentiation in vitro, also can suppress activity and the differentiation of osteoclast; Fructus Cnidii can raise the expression of the OPG gene in osteoblast, reduces the expression of RANKI, improves the ratio of OPG/RANKL, confirms that from gene level it can suppress the bone resorption of osteoclast.

Modern pharmacological research also proves, Fructus Cnidii can make mice with kidney-yang deficiency peritoneal macrophage phagocytic percentage and phagocytic index, serum hemolysin 50% haemolysis value, spleen lymph H-TdR mixes the indexs such as number and obviously raises, thereby strengthen the immunologic function of mice with kidney-yang deficiency, prompting Fructus Cnidii may be a kind of immunostimulant.Fructus Cnidii has anti-aging effects, can physical strength reinforcing, reduce blood cholesterol, improve immunity, regulate SOD and the horizontal aspect of gonadal hormone (estradiol/testosterone) all to have certain anti-aging effects, acute senile model memory deficits in mice is had to protective effect, its mechanism of action may be by strengthening antioxidase GSH-PX and SOD activity, remove the damage of oxygen-derived free radicals to central nervous system's neurocyte, also with it calcium antagonism expansion of cerebral vascular, to improve brain microcirculation relevant; Fructus Cnidii is resisting vascular smooth muscle propagation optionally, and research in recent years shows, osteoporosis and arteriosclerosis reciprocal causation, and Fructus Cnidii plays preventive and therapeutic effect by resisting vascular smooth muscle cell proliferation to osteoporosis; Fructus Cnidii can significantly increase the weight in wet base of mice accessory sex organ (testis, epididymis, seminal fluid capsule) and levator ani, and the rabbit of diethylstilbestrol enhanced sensitivity is strengthened in the effect of body uterus tension force, its amplitude obviously raises, uterus rhythmic exercise frequency also obviously improves, the period of motion extend and the activity time shortens relatively, the existing estrogen-like product of Fructus Cnidii is described, also has the existence of androgenic material.In the radioimmunoassay of testosterone and estradiol, further confirm in the extractive with organic solvent such as Fructus Cnidii, contain testosterone and estradiol sample material.In isolated experiment, prove the effect of the lax in vitro cavernous body of penis smooth muscle of Fructus Cnidii, may be to strengthen cGMP and (or) cAIVLP signal transduction pathway by the activity of inhibition phosphodiesterase, thereby promote sinusoid endotheliocyte to discharge NO, play a role.

This seminar of summary of the invention finds by the molecular compound Chinese medicinal preparation of Herba Epimedii, Margarita layer powder and cnidium monnieri, can warming the kidney to invigorate YANG, various osteoporosis are all had to good prevention and therapeutical effect.Herba Epimedii and Fructus Cnidii all have the kidney warming or kidney tonifying functions, and according to the traditional Chinese medical science " kidney governing bones " theory, kidney and bone have substantial connection, kidney can be accepted the essence that the vital organs of the human body pass, Feng Erzang it, enrich in bone, moisten and support in bone, the growth promoter of bone and the composition and the structure that maintain bone are normally had to important function.Modern medical theory is thought, " kidney governing bones " shows the hydroxylase system of kidney, the concentrating function of renal cells, the auxin of pituitary, parathyroid hormone and the calcitonin regulatory function to bone, so it is not limited only to kidney itself, closely related with other system especially hormonal system.Herba Epimedii can " kidney-replenishing, bone and muscle strengthening, curing rheumatism ", and Fructus Cnidii can " warming the kidney to invigorate YANG, dampness, dispel the wind, parasite killing ".Two medicines share the merit that can strengthen its kidney invigorating and YANG supporting, and the osteoporosis due to suffering from a deficiency of the kidney is prevented and treated.Modern medicine study proves, Herba Epimedii, Fructus Cnidii all has the effect of endocrine regulation, particularly can promote the secretory action of gonadal hormone, Margarita layer powder contains a large amount of calcium carbonate and the necessary various trace of human body without element and aminoacid, formation to sclerotin plays a very important role, the research in our past once proved that Herba Epimedii can prevent and treat the osteoporosis of castrated rats, osteoporosis to " yang deficiency " rat due to hydroxyurea also has preventive and therapeutic effect, main and the osteoblastic activity of its promotion of this effect of Herba Epimedii, promote that new bone formation is relevant, bone resorption is also had to certain inhibitory action.And our research also confirm the rat of Fructus Cnidii total coumarins to removal ovary osteoporosis, corticosteroid osteoporosis etc. is also had to obvious preventive and therapeutic effect.This effect of Fructus Cnidii, it is mainly the absorption that suppresses bone, new bone formation is also had to certain facilitation, but not as good as Herba Epimedii, celestial precious bone treasured share this two medicine, learns from other's strong points to offset one's weaknesses, heighten the effect of a treatment, Margarita layer powder, as calcium complement agent, has supplemented the synthetic essential raw material of bone, thereby has ensured that we bring into play positive effect in osteoporosis disease.

Pharmaceutical formulation and dosage by Herba Epimedii, Margarita layer powder and the molecular compound Chinese medicinal preparation of cnidium monnieri that the present invention proposes are as follows: Herba Epimedii 400g, and Fructus Cnidii 400g, Margarita layer powder 60g, this pharmaceutical formulation and dosage are made capsule, can make 1000.

The production technology by Herba Epimedii, Margarita layer powder and the molecular compound Chinese medicinal preparation of cnidium monnieri that the present invention proposes is: first get Herba Epimedii, Fructus Cnidii is ground into coarse powder, decoct with water three times, each 2 hours, merge three decocting liquids, filter, be concentrated into clear paste (relative density is 1.3～1.4), add the Margarita layer powder that is ground into micropowders, dry, pulverize for 80 DEG C, incapsulate, to obtain final product.

The production technology by Herba Epimedii, Margarita layer powder and the molecular compound Chinese medicinal preparation of cnidium monnieri that the present invention proposes, Margarita layer powder is to get 60 grams by every production 1000 capsules, is first ground into micropowders, and then interpolation enters in Effect of Chinese Medicine Qing cream.

The present invention propose by the molecular pharmaceutical formulation of Herba Epimedii, Margarita layer powder and cnidium monnieri and form consumption, also can add the adjuvant of pharmaceutics aspect, make soft capsule, tablet, granule, electuary, oral liquid is for clinical practice.

Detailed description of the invention:

Pharmaceutical formulation and production technology by Herba Epimedii, Margarita layer powder and the molecular compound Chinese medicinal preparation of cnidium monnieri that embodiment mono-proposes according to the present invention, get Chinese crude drug Herba Epimedii 400g, Fructus Cnidii 400g, Margarita layer powder 60g, carry out routinely after medical material qualification, first get Herba Epimedii, Fructus Cnidii is ground into coarse powder, decoct with water three times, each 2 hours, merge three decocting liquids, filter, be concentrated into clear paste (relative density is 1.3～1.4), add the Margarita layer powder that is ground into micropowders, dry, pulverize for 80 DEG C, incapsulate, make altogether 1000 of capsules.

Make by above pharmaceutical formulation and production technology containing Herba Epimedii, Margarita layer powder and the molecular compound Chinese medicinal preparation Xianzhengubao Capsules of cnidium monnieri, as hospital preparation, ratify through GDDA, use with doctor formula in our unit, last 20 years, prove that this preparation has warming the kidney to invigorate YANG, bone and muscle strengthening, wind-damp dispelling, the effect of prevention of osteoporosis, can be used for impotence and seminal emission, flaccidity of extremities, rheumatic arthralgia, numbness contracture, cold womb, cold-damp band inferior, to all kinds of osteoporotic obvious curative effects that all have, there is not untoward reaction.

Claims (6)

1. one kind has warming the kidney to invigorate YANG and prevents and treats the formula of osteoporotic Chinese medicine preparation, production technology and application thereof.

2. warming the kidney to invigorate YANG as claimed in claim 1 is prevented and treated formula and the production technology thereof of osteoporotic Chinese medicine preparation, it is characterized in that referring to that this Chinese medicine formula is every 1000 extracts that contain following Chinese medicine: Herba Epimedii 400g, Fructus Cnidii 400g, Margarita layer powder 60g.

3. warming the kidney to invigorate YANG as claimed in claim 1 is prevented and treated formula and the production technology thereof of osteoporotic Chinese medicine preparation, the production technology that it is characterized in that this Chinese medicine preparation be get Herba Epimedii, Fructus Cnidii is ground into coarse powder, decoct with water three times, each 2 hours, merge three decocting liquids, filter, be concentrated into clear paste (relative density is 1.3～1.4), add the Margarita layer powder that is ground into micropowders, dry, pulverize for 80 DEG C, incapsulate, to obtain final product.

4. warming the kidney to invigorate YANG as claimed in claim 3 is prevented and treated formula and the production technology thereof of osteoporotic Chinese medicine preparation, and it is characterized in that producing the dose that 1000 capsules Margarita layer powder used is ground into micropowders is 60 grams.

5. warming the kidney to invigorate YANG as claimed in claim 1 is prevented and treated formula and the production technology thereof of osteoporotic Chinese medicine preparation, it is characterized in that the formula of said preparation also can add the adjuvant of pharmaceutics aspect, makes soft capsule, tablet, and granule, electuary, oral liquid is for clinical practice.

6. the warming the kidney to invigorate YANG as described in claim 1～5 is prevented and treated osteoporotic Chinese medicine preparation, it is characterized in that said preparation has warming the kidney to invigorate YANG, bone and muscle strengthening, wind-damp dispelling effect, can be used for impotence and seminal emission, flaccidity of extremities, rheumatic arthralgia, numbness contracture, cold womb, cold-damp band inferior, treat all kinds of osteoporotic clinical symptoms.