CN1132606C - Medicine for curing coronary heart disease with hypertension and its preparation process - Google Patents

Abstract

The present invention relates to a Shanhaidan series medicine for treating coronary diseases associated with hypertension and a preparation process thereof, which belongs to the technical field of Chinese patent medicine and a preparation process thereof. The series medicine is composed of nineteen traditional Chinese medicinal materials of radix notoginseng, seaweed, membranous milkvetch root, etc.; in the preparation process, various experiments are carried out according to Provisions for New Drugs Approval, and three groups of file samples are repeatedly produced and are observed to show that the process is stable and is suitable for industrialization. Clinical observations in nearly ten years prove that the series medicine has the functions of nourishing qi and blood, dredging the channels, checking the exuberance of yang, effectively dilating the coronary arteries, increasing the blood flow volume of the cerebral arteries and coronary arteries, improving the oxygen supply of the heart muscles, adjusting blood pressure, reducing blood fat and enhancing immunity. The series medicine has the advantages of moderate and lasting drug effect, favorable short-term result and long-term follow-up result.

Description

The medicine and the preparation technology of treatment coronary heart disease with hypertension

The invention belongs to Chinese Traditional Medicines and fabricating technology field thereof, relate to a kind of SHANHAI PILL preparation series and preparation technology thereof who treats coronary heart disease with hypertension.

Coronary atherosclerotic heart disease is called for short coronary heart disease, and the sickness rate in total population is 11.8%, and is then higher in middle-aged and elderly people.Be that to cause clinically be the main cause that causes sudden death clinically.Before the present invention, the treatment coronary heart disease that patients with coronary heart disease is taken mainly is sorbitrate, nifedipine, persantin, SKF 33134A, diltiazem, slow heart rate, propranolol, propafenone, quinoline Buddhist nun fourth, the medicines such as the heart, SUXIAO JIUXIN WAN, FUFANG DANSHEN PIAN, Fel Ursi JIUXIN DAN, storax pill for treating coronary heart disease of living, these medicines are because of all being to pass through blood vessel dilating on pharmacology, temporarily solve the blood supply problem, so short term efficacy is in various degree all arranged, but late result is relatively poor, do not reach the purpose of healing, and take drug resistance and the toxic and side effects that all has in various degree for a long time.In recent years, the SHANHAI PILL Chinese patent medicine (ZL93101425.5) of DIAOXINXUE KANG and this institute has appearred, and all comparatively obvious to the late result of coronary heart disease, and without any side effects, be subjected to the welcome of extensive patients.Especially the SHANHAI PILL medicine series has carried out the typing medication at dissimilar in the coronary heart disease, obtained more obvious treatment effect, as (CN93101424.7), (CN93101423.9), come out and see ideal medicine at the special for treating medicine of coronary heart disease with hypertension type at the SHANHAI PILL medicine series " multiple arteries and veins spirit " of arrhythmia type coronary heart disease at the SHANHAI PILL medicine series " coronary disease gram " of angina pectoris.

Prior art situation at above-mentioned treatment coronary heart disease various kinds of drug, the objective of the invention is to, on the basis of the SHANHAI PILL Chinese patent medicine " patent No. ZL93101425.5; (91) medicine is defended (standard) word Z-50-2 number " that has clear and definite curative effect, continue the special medicament of exploitation, and provide and to guarantee its effective ingredient and preparation technology that can commercialization at the coronary heart disease with hypertension disease.

Now design of the present invention and technical solution are described below:

The present invention is according to clinical manifestations different on the coronary heart disease, through clinical and laboratory research in surplus ten years, and checking repeatedly, science is summed up and is formed.Coronary heart disease is divided into five kinds of conceal types, angina pectoris, myocardial infarction, arrhythmia type, sudden death type clinically.Because development speed, scope and the degree of position, scope, angiemphraxis degree and the deficiency myocardial blood supply of its pathological changes is different, many different symptoms can occur.It generally belongs to Chinese medicine " thoracic obstruction ", " angina pectoris ", " severe palpitation ", " precordial pain with cold limbs " category.With regard to its pathogenesis, relatively more consistent understanding is to be tending towards deficiency in origin and excess in superficiality, and deficiency in origin is based on the internal organs loss, and real the stasis with QI and blood of mark sees more.Hypertension belongs to generally that Chinese medicine is dizzy, the headache category, and relatively consensus is: this of disease is imbalance of YIN and YANG, disease be designated as interior living wind, expectorant, congestion.If hypertension further develops, blood pressure increases left chamber, back load and increases the weight of, myocardial hypertrophy, and ventricle enlarges.Persistent hypertension also helps lipid in deposition big, the medium-sized artery inner membrance, thereby coronary atherosclerosis takes place.These pathological changes mostly have hemodynamic variation and hypercoagulability, and high being attributable to fixed attention in " Blood stasis " of Chinese medicine.Coronary heart disease is if be associated with hypertension, and then its deficiency in origin and excess in superficiality embodiment is more obvious.

" element is asked an arthromyodynia piece of writing " said: " obstruction of heart-QI person, arteries and veins obstructed ".Pained disease and blood vessels obstruction close relation are described.And " Ling Shu Miraculous Pivot or Divine Axis sea opinion " said: " deficiency of marrow-reservoir, then vertigo and tinnitus "." Jing Yue's complete work is dizzy " piece of writing in also think: " no void can not be done dizzy ", " a dizzy disease, empty person occupy its eight or nine "." danxi's experiential therapy dizziness " then said: " dizziness, expectorant are held the deficiency of vital energy and fire under the arm, and it is main controlling expectorant, holds Qi-tonifying drug and pathogenic fire reducing medicine under the arm ".It is " emitting on the wind sun of liver and gall " that Hua Xiuyun thinks dizzy.In sum, although the cause of disease that causes a coronary heart disease and hypertension end by no means brings out etc. such as cold coagulation blood vessels, excessive rising of liver-YANG, the turbid heap soil or fertilizer over and around the roots Sheng of expectorant, diet, but with regard to its parallel operation, see with deficiency in origin and excess in superficiality that then deficiency in origin is based on qi-deficiency kidney-deficiency, mark is real to be seen with congestion, liver-wind more more.That is to say that because deficiency of vital energy promotion is unable, blood fortune is not smooth, the congestion retardance, heart arteries and veins is jammed; Deficiency of kidney yin, excessive rising of liver-YANG etc. are the important pathomechanisms that causes coronary heart disease and hypertension.Based on this understanding, the present invention is through a large amount of toxicitys, pharmacology, pharmacodynamic experiment and clinical verification repeatedly, and the Therapeutic Principle with " benefiting QI and nourishing blood, activating blood circulation to dissipate blood stasis, collateral dredging YANG hyperactivity suppressing " treatment coronary heart disease with hypertension disease has been determined in summing up experience.In the medicine with Radix Astragali QI invigorating and body resistance strengthening, the void of beneficial pectoral qi, and the dirty damage of the monarch that rectifies is abundant in order to do QI and blood, then blood fortune is unimpeded; Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling, nourishing blood to tranquillize the mind, and the effect of tonneau GUAN-pulse, pain relieving is arranged, the kind trusted subordinate's pain of controlling.Two medicines phase 5, the effect of playing benefiting qi and nourishing blood, blood circulation promoting and blood stasis dispelling is to be principal agent.The reinforcing of Radix Ginseng Rubra QI invigorating helps the power of Radix Astragali QI invigorating, and so pectoral qi is vigorous, and heartbeat is strong, then the sering tonneau; Flos Carthami promoting blood circulation to remove obstruction in the collateral, stasis-dispelling and pain-killing; The Radix Notoginseng removing stasis to stop bleeding, the analgesic therapy of invigorating blood circulation makes the stasis of blood go and just do not hindering; Pollen Typhae promoting the circulation of blood blood stasis dispelling can be controlled trusted subordinate's pain.More than four flavors can strengthen the power of Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling.The Rhizoma Cyperi Shugan Zhitong effect of regulating the flow of vital energy; The regulate the flow of vital energy merit of fast diaphragm, promoting the circulation of QI to relieve pain of Fructus Citri Sarcodactylis residence; Two medicines and medicine-feeding mutually 5 make mechanism of qi unimpeded, and then blood is capable stagnant; The Sargassum resolving phlegm and softening hard masses.The expectorant that coagulate in the stagnation of QI of can dispelling Tianjin, and the speckle of change arteriosclerosis; The Radix Paeoniae Alba yin fluid astringing that nourishes blood, easing the affected liver to relieve pain, " book on Chinese herbal medicine is not recorded " call its can " clear and coherent blood vessels ..., dispelling malignant blood, expelling extravasated blood ", and can suppressing liver-YANG, treating the liver sun rising dizzy; Semen Cassiae is bitter sweet and cool, and " book on Chinese herbal medicine justice " calls its " nourishing the liver and kidney with the justice of tranquillizing and subduing nourishing YIN, is controlling of reinforcing ", in order to the deficiency of YIN of invigorating the liver and kidney, and controls the liver-yang of rising; The Radix Achyranthis Bidentatae blood circulation promoting and blood stasis dispelling, the moon of invigorating the liver and kidney and promoting blood circulation both can increase the invigorate blood circulation effect of the colored stasis of blood of Radix Salviae Miltiorrhizae, and the headache that can treat hyperactivity of YANG due to deficiency of YIN, liver-wind stirring up internally again is dizzy; The Herba Epimedii reinforcing the kidney and supporting YANG is then agitated effectively in order to do the yang-energy abundance, and blood fortune is unimpeded, and the meaning of " kind nourishing YIN person must have treating YIN within YANG, then cloudy positive helping and source is inexhaustible " is arranged." Elementary Medicine " more call its can " the kidney invigorating void ..., control the hemiplegia hands and feet caused by paralysis, the extremity munbness "; More than four flavor invigorating the liver and kidney, dive liver-yang and mend the unsuccessful of principal agent, with Radix Ginseng Rubra, Flos Carthami etc. be ministerial drug altogether; The Radix Puerariae promoting the production of body fluid to quench thirst; The sharp joint of Ganoderma benefit vital essence; The Radix Polygoni Multiflori the liver benefiting that nourishes blood, the controlling nocturnal emission with astringent drugs kidney tonifying; Radix firmianae and blood vessels and the meridian dredging; The Radix Persicae removing blood stasis is stopped up and blood stasis expelling stagnates.The above five tastes one can be prevented the warm-dryness syndrome impairment of YIN of QI invigorating, QI regulating medicine, and one can increase the logical stagnant power of monarch drug activating blood circulation to dissipate blood stasis, is to be adjuvant drug.Semen sojae atricolor energy activating blood and promoting diuresis can be gone into kidney channel and the kidney invigorating void again, and nature and flavor are sweet flat, and the energy coordinating the actions of various ingredients in a prescription is to be messenger drug.All medicines share, and play the effect of benefiting QI and nourishing blood, activating blood circulation to dissipate blood stasis, collateral dredging YANG hyperactivity suppressing altogether.

Modern medicine thinks, cause of coronary heart disease mechanism mostly is coronary atherosclerotic and changes, and causes coronary stenosis or spasm, and coronary artery blood flow can not satisfy the needs of myocardial metabolism, due to the myocardial ischemia-anoxemia.And the narrow or spasm of arteria coronaria can make that blood flow is capable to become eddy current, impels platelet adhesion, assembles and form thrombosis.Hypertension then is the various factors combined influence, causes the regulatory function imbalance of blood pressure and produces.

According to above-mentioned Chinese and western medical scientific principle opinion, the composition and the proportioning of the SHANHAI PILL medicine series " Gao Guanping " of the treatment coronary heart disease with hypertension of the present invention's development are as follows:

The Radix Astragali 300～400 gram Radix Ginseng Rubra 60～80 gram Radix Salviae Miltiorrhizaes 60～80 grams

Yellow 50～70 grams of Radix Notoginseng 60～80 kairine sesames 60～80 grams

The Radix Paeoniae Alba 60～80 gram Flos Carthamis 60～80 gram Radix Puerariaes 20～40 grams

Radix Achyranthis Bidentatae 20～40 gram Semen Cassiaes 20～40 gram Fructus Citri Sarcodactylis 40～60 grams

Rhizoma Cyperi (processed) 60～80 gram Radix Persicae 40～60 gram Radix firmianaes 40～60 grams

Radix Polygoni Multiflori Preparata 40～60 gram Sargassums 40～60 gram Herba Epimedii 40～60 grams

Semen sojae atricolor 40～60 grams

The present invention is made up of said medicine, for the ease of clinical practice, has carried out screening, process rationality research and the study on the stability thereof of preparation.Through research, this product should adopt capsule formulation, both can cover bitterness, raising bioavailability and the medicine stability of medicine, characteristics such as have taking convenience again, be easy to carry about with one.Preparation technology's Rationality Study be according to each medicine physicochemical property, pharmacological action, in conjunction with the decision of combined factors such as clinical practice and production, be valuable medicinal as Radix Ginseng Rubra, Radix Notoginseng, if extract, composition easily loses, directly pulverize and be used as medicine, can reduce the loss, again can be as the excipient of preparation.The Rhizoma Cyperi main chemical compositions is a volatile oil, other contains alkaloid, cardiotonic glycoside, flavonoid etc., water of Rhizoma Cyperi or ethanol extraction have the effect of heart tonifying and decreased heart rate to the frog heart, and obvious hypotensive effect arranged, therefore should use distillating extracting oil, the reuse decocting boils once, to carry most effective ingredient, extraction time was advisable with 6 hours, and extractible volatile oil total amount is more than 95%.Monarch drug in the Radix Astragali side of being, its chemical constituent are chemical compounds such as pyrite class, Saponin class, polysaccharide, and main component is an astragaloside, and tool water solublity, polysaccharide are also water-soluble, so adopt water boiling and extraction; Flos Carthami contains Flos Carthami glycoside, Flos Carthami polysaccharide and organic acid, and its water extract can increase coronary flow, and alcohol extract does not then have obvious effect, and the water extract can obviously reduce the blood pressure of anesthetized cat and dog; Sargassum contains alginate jelly, mannitol, crude protein, iodine, potassium etc., and is all water-soluble; It is all water-soluble that Radix Achyranthis Bidentatae contains molting hormones such as ecdysterone, inokosterone, triterpenoid saponin, first salt etc.; Radix firmianae, Radix Persicae, Semen sojae atricolor are all water-soluble, so above-mentioned 7 kinds of medical materials are all selected water extraction.In the process that water is carried, amount of water, decocting time, decoction number of times are to influence the principal element that water is put forward effect, the present invention has carried out water and has proposed the conditional filtering test, take by weighing the recipe quantity medical material, test with Lg (3) orthogonal table, with astragaloside content serves as to detect index, adopts thin layer chromatography scanning to detect.Its result is: the secondary factors that influences astragaloside content is followed successively by and decocts number of times (C)＞amount of water (A)＞decocting time (B).So extraction process by water is defined as: decoct with water three times, each 0.5 hour, amount of water was 6 times of medical material total amount.Radix Salviae Miltiorrhizae in the medicine of the present invention, Pollen Typhae, Ganoderma, the Radix Paeoniae Alba, Radix Puerariae, Radix Polygoni Multiflori Preparata, Herba Epimedii, Fructus Citri Sarcodactylis, Semen Cassiae 9 flavor medical materials contain flavone, monoterpene composition paeoniflorin, volatile oil, Fructus Citri Limoniae Fructus Citri tangerinae lactone, foreign Herba Coriandri glycoside, hesperidin, ergosterol, fungal lysozyme, acid protease, anthraquinone analog compound etc. respectively, this constituents all has pure dissolubility, so select alcohol extraction.The Lg that the present invention carries out alcohol extraction process (2) orthogonal test, with the total flavones is to detect index, detect with colorimetry, its result is: the secondary factors that influences general flavone content is followed successively by: extraction time (D)＞extraction time (A)＞determining alcohol (B)＞alcohol adding amount (C), obtain preferred plan and be medical material with 70% alcohol reflux three times, each 2 hours, alcohol adding amount was 8 times.In addition, the present invention has carried out pilot scale to the technology that laboratory screening goes out, and has carried out the technology stability investigation by " provisions for new drugs approval ", through three batches of pharmaceutical factory pilot plant duplications of production and reserved sample observing, the result shows that this technology is stable, is fit to suitability for industrialized production.The preparation technology that the present invention determines is as described below:

More than 19 the flavor medical materials, Radix Ginseng Rubra and Radix Notoginseng powder are broken into fine powder, sieve; Rhizoma Cyperi (processed) extracted volatile oil 6 hours, and last medicinal residues add 5 times of water gagings and decocted 1.0 hours again, filtered, and the aqueous solution after filtrate and the distillation merges, and device is collected in addition; The Radix Astragali, Flos Carthami, Sargassum, Radix Achyranthis Bidentatae, Radix Persicae, Radix firmianae, Semen sojae atricolor decoct with water three times, and each 0.5 hour, amount of water was 6 times, and collecting decoction filters, and the medicinal liquid behind filtrate and the said extracted volatile oil merges, and is condensed into thick paste shape (relative density 1.20; 80 ℃), add ethanol, make that to contain the alcohol amount be 70%, stir evenly, cold preservation was left standstill 48 hours, filtered filtrate recycling ethanol; All the other nine flavor medical materials such as Radix Salviae Miltiorrhizae, Pollen Typhae were with 8 times of amount 70% alcohol reflux twice, each two hours, merge alcohol extract, filter filtrate recycling ethanol, water extract behind medicinal liquid and the above-mentioned recovery ethanol merges, and is concentrated into relative density 1.20～1.30 (40 ℃), after the spray drying, add Radix Ginseng Rubra, Radix Notoginseng fine powder, mixing sprays into volatile oil, and is encapsulated, make 1000 altogether, promptly.

" animal acute toxicity test report " of the present invention, " the Pharmacodynamic test of active extract report relevant with therapeutical effect ", " preparation preliminarily stabilised test report ", " preparation quality standard research report ", " clinical 200 routine case observation of curative effect report " provide (seeing Appendix 1,2,3,4,5) as the adnexa data of the present patent application.

The present invention belongs to the compound recipe pure Chinese medicinal preparation for the SHANHAI PILL medicine series " Gao Guanping " of treatment coronary heart disease with hypertension, effect with benefiting QI and nourishing blood, blood circulation promoting and blood stasis dispelling, collateral dredging YANG hyperactivity suppressing, effective coronary artery dilator, increase cerebral arteries and crown blood flow volume, improve myocardial oxygen delivery, reduce myocardial oxygen consumption, reduce peripheral vascular resistance, adjust blood pressure reduces the blood ester, enhancing immunity.Medicine effect of the present invention relaxes and lastingly, has near preferably, late result.

Claims (1)

1, the medicine of treatment coronary heart disease with hypertension is the compound recipe pure Chinese medicinal preparation, and it is characterized in that: its crude drug and proportioning are:

Radix Astragali 300-400 gram Radix Ginseng Rubra 60-80 gram Radix Salviae Miltiorrhizae 60-80 gram

Radix Notoginseng 60-80 kairine sesame 60-80 gram Pollen Typhae 50-70 gram

Radix Paeoniae Alba 60-80 gram Flos Carthami 60-80 gram Radix Puerariae 20-40 gram

Radix Achyranthis Bidentatae 20-40 gram Semen Cassiae 20-40 gram Fructus Citri Sarcodactylis 40-60 gram

Rhizoma Cyperi (processed) 60-80 gram Radix Persicae 40-60 gram Radix firmianae 40-60 gram

Radix Polygoni Multiflori Preparata 40-60 gram Sargassum 40-60 gram Herba Epimedii 40-60 gram

Semen sojae atricolor 40-60 gram.