CN87106235A - Treat atherosclerotic method and base composition - Google Patents

Abstract

The invention provides a kind of method for preparing base composition, compositions can reduce plasma cholesterol in fact in order to the treatment atherosclerosis, can reverse arterial plaque dirt deposition and the vascular degeneration relevant with atherosclerosis.The step of preparation method comprises the amino-acid mixed pH value that lumps together and regulate compositions within human blood pH allowed band of biological activity.Base composition also comprises biological activity Aminosteril KE solution as antiatherosclerotic.

Description

The present invention relates to atherosclerotic compositions of treatment and method, especially the atherosclerotic method of related treatment can solve the many different problems relevant with disease with base composition, has alleviated symptom in fact even has cured disease to a certain degree.The present invention is to use biological activity Aminosteril KE (L-formula) to achieve the goal.

In the U.S. and West Europe, cardiovascular diseases and disease associated with it, malfunction and complication are permanent disability and main causes of death.A kind of special disease that obviously belongs to the physiological pathology aspect is that atherosclerosis it is generally acknowledged that this is the reason that causes mortality rate and key health expenses to increase.The number that the U.S. dies from coronary artery disease every year merely in the past per 5 years has just surpassed 550,000.In addition, annual number because of atherosclerotic complication-myocardial infarction hospitalization has also surpassed 680,000, and number is also growing steadily.In the last few years, dying from atherosclerotic number in the U.S. has surpassed and has died from cancer, the summation of wound and infectious disease number.

Nineteen eighty-three, be directly used in the expense of handling aspect patients with coronary heart disease healthy in the U.S. and surpassed 8,000,000,000 dollars.Same time, this country singly was used for the atherosis total expense of coronary heart disease medium-sized artery above 60,000,000,000 dollars, and estimated in 1987 to arrive 96,000,000,000 dollars.These expenses even do not reflect that also those are used to handle the cost of many different non-heart disease situations, these diseases are also caused by atherosclerosis.

Atherosclerotic genius morbi is that fatty material (mainly being cholesterol) deposits also fibrosis then at the arteries internal layer, causes the speckle dirt in arterial wall surface deposition and degeneration.Ubiquitous tremulous pulse fatty spew dirt is atherosclerotic early stage infringement (even also often finding this kind symptom in the child), the speckle dirt is a kind of stiff fat, the lipid sebum glandular sac of being made up of macrophage (leukocyte) and some smooth muscles fibers.Speckle dirt fibrosis is represented the development and change of atherosclerosis later stage, and it makes connective tissue matrix and contain in the cell of variable and extracellular lipid gas has been lived the smooth muscles cell of tunica intima.Thisly be positioned at being covered by the dense fibrous cap of smooth muscles or connective tissue usually of lumen of artery surface.Under fibrous cap, the high cyton that damage is made up of macrophage, other leukocyte and smooth muscles cell is a cholesterol crystal in the deep at this a large amount of cell aggregationes position, the downright bad fragment and the zone of calcification material.

If disease continues development, will cause the narrow and obstruction of arterial blood tube chamber, cause blood flow to reduce or obturation, cause the main organs or the region of anatomy then, as brain, heart, partial ischemia of intestinal or extremity or infraction.Consequently loss of function, the forfeiture cellular material causes and adopts first aid medicine and/or surgical operation, even and can cause permanent disability dead.In addition, lipid (cholesterol), inflammatory leukocyte, connective tissue and calcification material soak into Musclar layer, have seriously weakened the arterial blood tube wall, cause some position deliquescing of blood vessel wall and/or become fragile, form demi-inflation (hemangioma) and break, and cause organ, the hemorrhage even life-threatening of limbs.

And atherosclerotic cause is not also got clear fully, and is relevant with plasma cholesterol and lipid content according to many research worker and clinician's this imbalance of clinical observation experience inference.The better mode that the general therapeutic arteries is atherosis comprises: Drug therapy, put somebody on a diet, and change the action mode and carry out motion exercise with control and minimizing blood plasma cholesterol level.

The medicine that is generally used for reducing blood plasma cholesterol level comprises clofibrate, gemfibrozil, dextrothyroxine sodium, cholestipol, probacol, nicotinic acid and cholestyramine.These medicines only are to treat and inoperative to the atherosis result of arteries at the cause of disease in general.And to the speckle dirt deposition being reversed and the degeneration reverse aspect in the arterial blood tube wall not being acted on.These medicaments also have many other shortcomings, as: deleterious pair of effect (hypertension, arrhythmia, gastrointestinal upset, headache, irritated or the like), contraindication (heart disease, hepatopathy or nephropathy, gestation or the like), need conscientiously to take medicine all the life, patient accomplishes it is difficult consistently, durability often changes, and medicine expense height.

In case PD is to the remarkable stage that continues symptom and jeopardize cardiac function, next step therapy is taked artery bypass grafting to transplant usually to repair and/or is replaced the pathological changes tremulous pulse.Though coronary bypass-forming operation has become a kind of in many common cardiovascular surgical procedures in the U.S., but clearly surgical operation does not solve pathologic problems, because it does not play and stops or twisting action on PD, and only is possible where necessary by arterial shunt is overcome the most critical pathological changes tremulous pulse momently.Further, the inadequate surgical operation of accepting of patient is with the obvious risk of M ﹠ M.Really, when operation was carried out, the state of an illness may continue in development, and vein or the tremulous pulse of itself often crossed the tremulous pulse of disease infringement after the operation, and it causes that atherosclerotic speed is faster than original pathological changes tremulous pulse on the contrary.In addition, by national heart, the conclusion that the research of coronary artery surgery that lung and Blood Research Institute (NHLBI) are sponsored draws is with the surgical operation therapy patient and heals with medicine between the patient at survival rate or develop into and generally do not have statistical significance aspect the myocardial infarction rate.

As the operating other method of crown shunting is to adopt some medicines and method to treat the result that atherosclerosis causes, rather than the treatment cause of disease.These therapies comprise the chelation therapy that has edta edta and the coronary angioplasty (PTCA) of skin transfer chamber.Yet the EDTA therapy still is in the experiment, and their benefit and ill effect also imperfectly understand and remain further to be familiar with.The PTCA therapy is because harmfulness has limited application, and it produces the lethal complication sometimes.The application of the vaporific carburator of senior experiment intra-arterial laser beam speckle is restricted, and operation is with near the pathological changes vascular because it need be begun to speak.

Find unexpectedly now that non-intestinal takes the solution that contains some biological activity ispols and can reduce blood plasma cholesterol level (concentration) significantly arterial plaque is deposited and take a turn for the worse with the vascular degeneration relevant with atherosclerosis.

Because medically all, non-intestinal vein has used some Freamines in 30 to 40 years in the past.

For whole non-enteral nutrition thing (TPN) or intravenous supernutrition, the existing existing technology that extensively is suitable for solves patient's nutrition and metabolism problem, and this class patient can not or should not absorb and absorbs enough best nutritional substrate by digestive tract.Really, this technology of being created by the present inventor has been successfully used to support a baby and a child's more than 15 years old normal development and growth.

At present, have many standard TNP solution to have bought on market in the U.S., it comprises the TPN solution TRAVOSOL(Travenol laboratory product of following trade name), EREAM INE(Mc Gaw Laboratory Production).AM INO SYN(Abbott Laboratory Production) and NO-VAM INE(Cutter Medical, Divisian of Miles laboratory).These standard intravenous nutritional solutions are balanced in nutrition, with they be made into can provide that general patient needs contain heat, protein (aminoacid), vitamin, mineral, the nutritional solution of water and trace element.Composition in these solution can use according to a certain percentage, and can in the course of treatment, the special requirement according to patient be made into special special solution by doctor and pharmacists, in order to satisfy the special nutritional need of patient, the calorie of essential fatty acid and increase also can lipids form be used to patient respectively by vein as the reinforcement Emulsion of Semen sojae atricolor or Oleum Helianthi.For suffering from nephropathy, the patient of hepatopathy or serious symptoms, special-purpose aminoacid vein ingredients also can have been bought in market, and it is to handle these situations by adding adjuvant.For example, United States Patent (USP) N _o.3,832,456 have introduced aminoacid uses United States Patent (USP) N as nutrient _o.3,950,529 introduced the aminoacid that the hepatopath uses.

But the biological activity Freamine that nobody proposed parenterai administration can be used to treat atherosclerosis, especially is used for reversing the harmful complication that links to each other with this disease.

Therefore, the purpose of this invention is to provide a kind of preparation and be used for treating atherosclerotic aminoacid prescription method, this prescription can not only reduce blood plasma cholesterol level (concentration) (causing pathogenic factor), and can suppress, reverse even cure speckle calm and degeneration tremulous pulse (result) and the secondary complication that links to each other with this disease to a certain extent.

The present invention also provides a kind of preparation to be used for treating atherosclerotic aminoacid prescription method, and this prescription does not produce many pairs of effects of general Drug therapy and can reduce even eliminate surgical operation or other therapeutic method of surgery that most of atherosclerotic adopts effectively.

The invention provides preparation and be used for the treatment of atherosclerotic prescription, this disease with following described be feature: the fatty material calmness causes speckle calmness and arteriasis in endarterium and fibrosis.The concrete advantage of the present invention prescription is that they can reduce blood plasma cholesterol level significantly, can suppress again, reverses even cures arterial plaque calmness and the vascular wall degeneration relevant with atherosclerosis to a certain extent.

The invention provides preparation atherosclerosis formulation method especially, this reagent can reduce blood plasma cholesterol level and reverse arterial plaque calmness and the vascular degeneration relevant with atherosclerosis, and it contains biological activity aminoacid, and is made into by following step:

(A) make up following material:

3% to 10% isoleucine

3% to 10% leucine

About 2.5% to about 7.5% lysine

About 2.5% to 7.5% methionine

About 3% to about 10% phenylalanine

About 1% to about 4% threonine

About 1% to about 3% tryptophan

About 3% to about 10% valine

About 2% to about 20% alanine

About 7% to about 20% arginine

About 1% to about 4% histidine

About 0% to about 4% proline

About 0% to about 8% serine

About 0% to about 1% tyrosine

About 0% to about 10% glycine

About 0% to about 6% glutamic acid

About 0% to about 6% aspartic acid

About 0% to about 1% cysteine

Its percentage by weight is meant and accounts for the amino acid whose percentage by weight of whole described biological activity that said aminoacid preferably is selected from acetate, the crystallization of chloride and hydrochlorate;

(B) balance is used for the ion of described salt.

(C) add non-toxic organic compounds with the PH that regulates medicament in the scope that human blood PH allows.

The present invention also provides the method for preparing the aqueous solution of the antiatherosclerotic agent that is used for parenterai administration.

According to general plotting, the of the present invention prescription to small part comprises a kind of active antiatherosclerotic agent, and this medicament contains the amino acid whose compositions of biological activity (L-type) in addition.This aminoacid prescription preferably contains arginine and branched-chain amino acid at least, isoleucine, and leucine and valine, wherein arginine preferably is present in the mixture with the maximum percentage by weight that accounts for whole aminoacid weight.Better prescription also comprises lysine, methionine, phenylalanine, threonine, tryptophan, and histidine.Best prescription comprises alanine, proline, serine, tyrosine, glycine, glutamic acid, aspartic acid and cysteine.

The prescription of this method also comprises other aminoacid according to patient's special requirement, other nutrient or additive, and as vitamin, mineral, electrolyte, carbohydrate, antibiotic, anticoagulant etc.

The compositions of this method is preferably passed through a central vein conduit parenterai administration with the aqueous solution form, because suitable aqueous solution has hypertonicity.Preferably every day quantitative aqueous solution is imported administration by a venoclysis pump continuously consistently from vein.

This method product major advantage that is used for the treatment of the atherosclerotic and contains other compositions comprises as follows:

Blood plasma cholesterol level can reduce quickly and fall than any earlier Drug therapy is arranged and reached bigger; Degree that atherosclerotic plaque disappears and scope are than previous once showed bigger; Reverse treatment time that atherosclerotic plaque needs and speckle from original compare to the time that grows up to relative short; In the dosage range of doctor's advice during administration, all solution compolisions all are the toxicity and pay the biological activity nutrient of reaction of can ignoring; With the present composition and other medicines and surgical operation cost and effectiveness and benefit ratio relatively from paying, aspect the treatment atherosclerosis the former both are more favourable than the back; This therapy can begin and carries out fully the outpatient; The treatment of this method and at be atherosclerotic basic pathology physiology, be reach therapeutic purposes with approach biochemistry by initial, rather than by pharmacology or treat by the surgical operation approach that only relates to the atherosclerosis complication.

These and other feature and advantage of the present invention can make the very fast understanding of those people that know this area by following detailed and the embodiment that has with reference to figure.

What Fig. 1 represented is the daily total cholesterol density of blood plasma of patient, and these patients treat by the method that embodiment 2 describes, and the reaction result of demonstration obtains by the composition that changes injectant.

According to described, this method provides treatment atherosclerotic substrate composition, and above-mentioned atherosclerosis is with fatty material, initial cholesterol as speckle then the fibrosis calmness be the disease of feature on endarterium.According to described, it is relevant with plasma cholesterol and lipid levels to small part that atherosclerosis is considered to.

The compositions and methods of the invention can reduce blood plasma cholesterol level (promotion reason) and reach by reversing arterial plaque calmness and vascular wall degeneration (result) thereby inhibition respectively, slow down so that this disease of healing to a certain degree, solving many problems relevant with this disease, aspects such as situation and secondary disease are effective especially.

According to general plotting, compositions of the present invention contains biological substrate, and this biological substrate comprises a kind of atherosclerosis preparation at least in part.Atherosclerosis preparation used herein has the Denaturation that reduces blood plasma cholesterol level and inhibition and reverse arterial plaque calmness and arterial wall.Specifically, active atherosclerosis preparation is that biological activity is amino acid whose, especially L-type aminoacid.

Biological activity aminoacid is divided into essential with nonessential usually.Essential amino acids refers to that those can not synthesize and must absorb the aminoacid of q.s in vivo from food.Non essential amino acid is meant the biosynthetic in vivo aminoacid of those available other substrates.Usually being divided into essential amino acid has: isoleucine, leucine, and lysine, methionine, phenylalanine, threonine, tryptophan, and valine.Non essential amino acid has: alanine, arginine, histidine, proline, serine, tyrosine, glycine, glutamic acid, aspartic acid, cysteine.Arginine and histidine are considered to half and essential are that they are essential for the baby and also are essential to a certain extent to the kidney patient.

These biological activity aminoacid have dextrorotation D-type and left-handed L-type.The L-type is considered to than D-type higher biological activity is arranged, and therefore, preferably the L-type is used for the atherosclerosis preparation.

Substrate composition of the present invention places aqueous solution, then as the therapeutic agent parenterai administration in the patient.When taking this administration, compositions of the present invention has reduced blood plasma cholesterol level really and has reversed arterial plaque calmness and vascular wall degeneration.

The atherosclerosis preparation preferably contains arginine at least, isoleucine, and the mixture of leucine and valine, wherein arginine preferably accounts for the maximum percentage by weight of whole biological activity aminoacid weight in the mixture.These aminoacid preferably account at least aminoacid heavy 25%, but be used for of short duration infusion during the cycle, can be unique active ingredient.This mixture also comprises various other aminoacid.Thereby preferably all aminoacid above-mentioned are present in all aminoacid other composition in nutritive equilibrium liquid are used.All these compositions all are TPN solution parts, but be to increase branched-chain amino acid and arginine concentration unexpectedly, usually be accompanied by the minimizing of histidine amount in the ispol, the result causes blood plasma cholesterol level (an about week) significantly (common 40% to 60%) reduction in time.Another is noted that simple amino acid whose minimizing in the TPN solution, especially refers to alanine and glycine, particularly glycine.

Below the approximate weight percentage range that is contained in the aminoacid in the better ispol and accounts for whole aminoacid weight in the mixture is listed in the table I.

The table I

Aminoacid approximate weight % aminoacid approximate weight %

Isoleucine 3-10 alanine 2-20

Leucine 3-10 histidine 1-4

Lysine 2.5-7.5 proline 0-10

Methionine 2.5-7.5 serine 0-8

Phenylalanine-3,4-quinone-10 tyrosine 0-1

Threonine 1-4 glycine 0-10

Tryptophan 1-3 glutamic acid 0-6

Valine 3-10 aspartic acid 0-6

Arginine 7-20 cysteine 0-1

It should be noted that the non essential amino acid listed is above recovering littler than the effect of other kind amino acid as the sensu lato any composition of the present invention to atherosclerosis, for alanine with not have the aminoacid of side chain also be same in fact.When patient needed time several months, from nutritional point, these aminoacid were important.According to the above, these aminoacid add than on the listed character and the advantage of Duo or can not influencing or change this solution less of table, therefore, do not influence enforcement of the present invention.Like this, table II below the approximate weight percentage range that is contained in the following aminoacid in the better ispol and accounts for whole aminoacid weight in the mixture is listed in.

The table II

Aminoacid approximate weight percentage ratio aminoacid approximate weight percentage ratio

Isoleucine 4-10 alanine 7-16

Leucine 5-10 histidine 1.5-3.5

Lysine 4.5-6.5 proline-4 .5-3.5

Methionine 3.5-5.5 serine 2.5-8.5

Phenylalanine 4.5-7.5 tyrosine 0-1

Threonine 2-3.5 glycine 3-8

Tryptophan 1-2.5 glutamic acid 3.5-5.5

Valine 4-9 aspartic acid 2-4

Arginine 9-18 cysteine 0-1

Above-mentioned ispol preferably is prepared by the method that the aminoacid of crystal form (normally acetate, chloride or hydrochlorate) is mixed.Used each ion should reach balance and broken to avoid the intravital acid-base balance of patient in the salt, often adopts about 80% acetate, 20% chloride and hydrochlorate.The pH value of solution of the present invention generally can be about 5.0 to about 7.8 scopes, but preferably be adjusted to identical with the pH value of blood, promptly about 7.39; Can adopt the method that adds a kind of suitable avirulence organic compound during adjusting.The aminoacid of selecting crystal form for use is because of its purity height, and can accurately regenerate corresponding aminoacid by the aminoacid of crystal form.Moreover the solution made from the aminoacid of crystal form can directly assimilate in vivo, needs every day in vivo earlier through biological agent.Above-mentioned ispol also can be prepared like this, and nutrition (TPN) liquid that adopts commercially available parenteral to use adds aminoacid therein, preferably adds the aminoacid of crystal form, promptly obtains solution of the present invention.Available TPN liquid comprises that trade mark is a class TPN liquid of " Travasol ".

In addition, can contain some other basic nutrient in the present composition, have the composition of nutrition, antibiotic, anticoagulation and some other biological support substance of being understood for the ripe refining personnel in present technique field as vitamin, mineral, electrolyte, carbohydrate, antibiotics, anticoagulant etc.But the best group compound depends on patient's concrete condition, and this all is the same in nearly all biological applications field; That is to say that the ispol of practical application can be adjusted according to the following general compositions of administration and the factor of dosage of determining, for example, concrete patient is to the reaction of composition therefor; Concrete patient is to toleration single and that mix composition; Disease progression stage and ill degree; Major organs that disease is damaged (one or more organ) or system (one or more system); By the main biological function of disease and/or the infringement of its complication, patient's occurring together property malnutrition, existence, character and the intensity of clinical syndrome; The recovery stage and for palliate a disease and/or the symptom of its complication and symptom and taking performed the operation or other method after stage; Patient's age, sex and general situation; The generation of other occurring together property disease (diabetes, familial hyperlipemia etc.); And the factor that other one skilled in the art understood.

Above-mentioned factor all use with the patient or the tolerance present composition in ispol and the ability of other composition relation is arranged.In other words, because one or more above-listed factors, to each patient, the different phase in treatment all may need some concrete compositions are done certain adjustment.For example, perhaps patient that diabetes are arranged can not tolerate and not have the heat production composition of the as many sugar form of patient of diabetes.Again for example, the people's of known patient's kidney or liver failure amino acid requirement is different with the people who does not have these symptoms.Give an example, with mn physiognomy ratio, underfed people may need more with different aminoacid and other nutrient again.Those skilled in the art can recognize these special requirements, also can adjust compositions of the present invention in view of the above.

Can also carry out other adjustment to amino acid whose mixture according to the aminoacid distribution situation of blood or urine.These scattergrams can reflect that health is to every kind of concrete amino acid whose situation of utilizing; According to these scattergrams, can determine to lack in the body that seed amino acid, perhaps.The sort of aminoacid is excessive, thereby can be compensated by adjusting above-mentioned ispol.This seed amino acid scattergram is once making needed adjustment according to it through definite those skilled in the art.Determine that by blood and urinalysis patient body utilizes amino acid whose situation, and according to analysis result aminoacid is distributed and to adjust.We find that antiatherogenic effect depends on the aminoacid and the arginic amount of the side chain that uses to a great extent in treatment.Up to the present, ignored by people as a kind of arginic Special Significance of important amino acid always, and unexpectedly appeared in practice of the present invention: arginine is a kind of aminoacid that significant contribution is arranged.

The present composition is preferably with quiet water filling solution form parenteral.Therefore this aqueous solution contains as the above-mentioned composition and a kind of aqueous solvent substrate that are added on the solute in the solution.The deionized water substrate that aqueous solvent substrate is preferably aseptic wherein can add some compositions, and this depends on the composition of ispol and the concrete needs of individual patient.For example, if the calorific value of compositions is not enough, and needs of patients picked-up more heat, then this aqueous solvent substrate can be glucose-water, fructose-water or Nulomoline-water (glucose and the fructose that contain equivalent), the carbohydrate substrate that wherein contains variable concentrations, these substrates are for satisfying the patient demand of heat to be selected for use.Above-mentioned solution can adopt aseptic, the anticorrosion and pharmaceutical chemistry method that right and wrong Changshu is known the those of skill in the art in this area that have been shaped to prepare, to guarantee that each composition can dissolve fully, simultaneously can keep stability, aseptic, safety, and to guarantee to obtain to individual patient be preparation preferably.

The antiatherosclerotic that preferably contains effective dose in the solution, it is ispol, so that after the supernutrition method of knowing with those skilled in the art is with the solution parenteral, in the short period of time, normally in two to six months, (supplying with the needed nutrition that earns a bare living during this period in patient's body) can produce following effect: plasma cholesterol is obviously descended, the degeneration change procedure of artery plaque deposition and arterial wall is significantly reversed.The concentration of ispol can have only 4 grams (account for solution weight 4%) in the scope of the solubility limit of concrete ispol in specific aqueous solvent (sometimes up to solution weight 20%) in aminoacid gross weight from low per at least hundred ml solns in the aqueous solution.The concentration of ispol is preferably in the following ranges in the solution, and the aminoacid gross weight is about 7.5 to about 12 grams (account for solution weight 7.5～12%) in per hundred ml solns.Adopt above-mentioned concentration can make a kind of hyperosmotic solution (every liter 800～1100 milliosmolarity), promptly the osmotic pressure of this solution is greater than blood (every liter 290～310 milliosmolarity), and its meaning is the discussion of face as follows.For above-mentioned concrete compositions useful, the concentration of ispol is preferably in per hundred ml solns about 9 to about 11 grams in the solution, is more preferably about 10 to the amino acid whose scope of about 11 grams.

The administering mode of aqueous solution of the present invention is a parenteral but not oral because oral many shortcomings are arranged, oral after, aminoacid is subjected to the modification Digestion of stomach, intestinal, pancreas regulating liver-QI; Endogenous cycle produces a kind of cushioning effect to the composition in the preparation; Determine a kind of model of solution for oral use, the concentration of atherosclerosis activating agent in the blood of oral back is reached and direct vein titration after produce the same, this is difficult; Be difficult to set up and keep accurately controlling the method for intake.Adopt the parenteral mode, can the direct aggression target tissue, in some cases, even the part that can isolate health is poured into it with Freamine, infusion time can be several hours, several days or a few week, and can acutely not change patient's normal nutrition pattern.In addition, adopt parenteral can also realize the constant administration of control, can guarantee the persistence of curative effect like this, thereby can avoid the big rise and big fall of curative effect, and this phenomenon to occur in the absorption carried out after oral or the enteral administration and the assimilation process be inevitable.

Selected aqueous solution can be (about 800 to about 1100 milliosmolaritys/liter) that height oozes, so should make this class solution enter the high major diameter blood vessel of blood flow during intravenous administration, thereby reach the effect of diluting at once basically, preferably solution being imported this conduit of central vein conduit during quiet notes is any proper method of knowing according to those skilled in the art, and it is endovascular that percutaneous is inserted into superior vena cava.In one piece of article of O ' Donnell, Clague and Dudrick, introduced a kind of good intubation, this article exercise question is " Percutaneous Insertion of a Cuffed Catheter with a long Subcutaneous Tunnel for Intravenous Hyperalimentation ", be published in southern medical science magazine the 76th volume, o.11 (1983), the 1344-1348 page or leaf, this article incorporates its full content in this into own forces by reference.

Conduit just can begin to carry out continual instillation with the atherosclerosis aqueous solution after inserting.The day instillation total amount of solution for single patient, is to be enough to reach to per kilogram of body weight, provides about 0.25～3.5 gram in per 24 hours, is more preferably the amino acid whose amount of about 1～2 gram.It also is comparatively ideal that above-mentioned solution consumption per day adopts commercially available quiet notes pump to feed from intravenous continuously and consistently, can make the vivo acid level keep stable like this.

In the process of the infusion of therapeutic that continues, generally be about two months to about eight months, had better not allow the patient absorb can influence vivo acid balance or metabolic other Nutrition thing.The patient can drink the liquid of no nutrition, may need some medicaments that use in also can the oral medication process.For some particular patients ', can be according to not lying in bed or outpatient's way, use pocket lightweight pump and support the instillation that device carries out solution of spreading that solution, drip tube and pump use.Even to some patient more specifically, the titration in 12～16 hours of 24-hour a day day dropped amount, allow the patient break away from quiet notes pump and drop instillator every day 8～12 hours, make they in the non-instillation time, have bigger freedom and can activity once, doing like this may be better.When the patient breaks away from infusion tube,, be necessary in centre pipe, to inject 1～2 milliliter every milliliter heparin solution that contains 100 units approximately, use asepsis plug (for example Luer-lock) then its jam-pack for the prevention conduit is stopped up by blood clot.

In the first few weeks of infusion atherosclerosis solution, should patient's situation be monitored by blood sample or urine sample biochemical method, hematology's method and metabolic approach every one to three day.Can make the blood and/or the urine amino acid scattergram of sample when needing, according to this figure ispol be adjusted then.If any above-mentioned adjustment that can carry out along with the infusion of above-mentioned aqueous solution and to the initial composition of solution in these aminoacid indexs of beginning and become stable just can be being extended for for 1～2 week the blanking time of monitoring.

Other index to be monitored comprises: serum cholesterol; cholesteryl ester; apolipoproteins A; apolipoproteins B; high density lipoprotein (HDL); cholesterol; triglyceride; sodium; potassium; chloride; bicarbonate; kreatinin; calcium; Phos; glucose; urea nitrogen; uric acid; total protein; albumin; the gallbladder sanguinin; alkali phosphatase; lactic acid dehydrogenase (LDH); serum glutamic oxalacetic transaminase (SGOT); serum glutamic pyruvic transaminase (SGPT); gamma glutamyitransferase (GGT); creatine phosphokinase (CPK); magnesium; zinc; copper; blood coagulation zymogen time (blood prothrombin time); the portion of tissue thrombokinase time (partialthromboplast in time); numeration of leukocyte; red blood cell count(RBC); hemoglobin; leucocrit; mean corpuscular volume; average grain shape hemoglobin (mean corpuscular hemoglobin); average grain shape hemoglobin concentration); differential blood count and platelet count.These code tests can be carried out separately.Grouping is carried out or is carried out together, to guarantee safety and curative effect, the maintenance homoiostasis for the treatment of and further to help the clinicist to carry out the adjustment of solution at individual patient.

Gone through the present invention above, enumerated some instantiations below again it is described further.These examples are explanation rather than restriction foregoing invention just.

Embodiment 1

The proof cholesterol is that the trial that causes one of atherosclerotic principal element is subjected to certain always and hinders, because single-pass is crossed and adjusted diet and/or adopt chemical therapeutic method can not reduce serum cholesterol level and keep the serum cholesterol level that has reduced.In a series of tests in advance, by adjusting the diet of New Zealand albinism rabbit, turn out a kind of atherosclerosis animal model with several years.In some researchs, use a hundreds of adult male rabbit and female rabbit, continuously and meet and logically adjust its diet, the result turns out a collection of neat reliable animal model, is used in these albefaction rabbits and brings out atherosclerosis on one's body; The atherosclerosis of bringing out out distribute, each pathology stage and aspects such as seriousness, gross morphology and histological characteristic, basic pathology physiology, secondary complication and clinical manifestation are all similar with the human atherosclerosis put down in writing on viewed and the document.

As herbivore, rabbit generally can only digest cholesterol contained in a bit and a sup.Because the liver of rabbit can not be removed a large amount of food cholesterol by biochemical process, causes plasma cholesterol concentration to increase rapidly.Plasma cholesterol concentration increases and causes reproducible, the atherosclerosis of high-stage more within a certain period of time; Atherosclerotic degree, outward appearance and scope are all consistent with the raising and the hypercholesteremia persistent period of plasma cholesterol concentration.

In above-mentioned research in advance, make and a kind ofly cause atherosclerotic food and use it for an other hundreds of rabbit and bring out atherosclerosis on one's body; These rabbits are used as the main body in the later research.In a cross-section study, 40 New Zealand's albinism adult male rabbit and female rabbit all feed with a kind of basic experiment rabbit food (Teklad T.D.82135); This rabbit food is heavy by being used as 2%() the 8%(of carrier of crystallization cholesterol heavy) the reinforced high fiber Purina Labchow 5326 of Oleum Arachidis hypogaeae semen constitutes.After beginning to feed to above-mentioned experimental rabbit food, at ten days in two weeks, the blood plasma cholesterol level of rabbit rises to more than 1000 milligrams/deciliter, and in all the other times in initiation atherosclerosis period in six weeks altogether it is remained between 1000 and 2000 milligrams/deciliter.

Six time-of-weeks, one mistake is killed 10 rabbits, and is made necropsy, to describe, to write down the observed development degree of atherosclerotic macroscopic view and microscopically, stage and scope, as a datum mark.All the other 30 rabbits in the preliminary examination group are divided into three seminar randomly.10 experimental animals are arranged in first group, they are continued to feed with the above-mentioned atherosclerosis food that causes, continue other six time-of-weeks.10 experimental animals of second group are fed with code test rabbit (Teklad T.D.82135) food, wherein do not contain Oleum Arachidis hypogaeae semen and crystallization cholesterol, continue for six weeks.To a kind of six weeks of atherosclerosis solution of 10 animal continuous infusions of the 3rd group; Infusion is to be undertaken by the central vein conduit that is inserted in the superior vena cava; The insertion method of conduit is that those skilled in the art are known.It is heavy to contain 4.25%() aminoacid and 25%(heavy) the aminoacid of atherosclerosis solution of glucose form the III (A hurdle) that is listed in the table below.The administered dose of this solution should satisfy can provide the aminoacid of 1.5 grams and the heat of 35 cards to per kilogram of body weight every day; Go back vitaminize, mineral and trace element in the solution, to make the mixture of nutritive equilibrium.

The table III

Aminoacid weight % aminoacid weight %

A B A B

Isoleucine 4.7 6.3 alanine 20 15.8

Leucine 5.9 7.4 histidine 4.1 3.2

Lysine 5.9 6.3 proline 9.4 8.4

Methionine 5.9 5.3 serines 7.0 6.3

Phenylalanine 5.9 6.3 tyrosine 0.5 0.4

Threonine 3.5 3.2 glycine 9.4 6.3

Tryptophan 2.4 2.1 glutamic acid-3.2

Valine 4.7 6.3 aspartic acids-2.1

Arginine 10.0 10.5 cysteine 0.7 0.6

In the research end of term in second six week, 30 rabbits are all put to death and dissect corpse to determine and to trace atherosclerotic seriousness, period and distribution.In first group of rabbit, induced baroque atherosclerotic lesion; This focus can repeat and as one man involve 85%～95% and originate from heart and lead to the ramose aorta of common iliac artery, has the surperficial speckle dirt pattern and the arterial wall characteristic distributions of viewed atherosclerotic lesion in the people.There are indications that several rabbits in first group suffer from the anthropoid myocardial infarction of class, cerebral thrombosis, intestinal ischemia and intestinal obstruction, and hind leg ischemia and blood vessel infraction.

Fed the rabbit in six weeks with standard test rabbit food for second group, compared, do not demonstrated the degeneration of atherosclerotic plaque dirt with initial those sacrificed 10 rabbits in group feed atherogenicity diet six weeks back.On the contrary, during this second six week, the atherosclerosis of second group of rabbit also slightly gets along with.

Yet in accepting the 3rd group of rabbit of above-mentioned special atherosclerosis preparation venous, the significant degeneration appears in the atherosclerotic plaque dirt.In fact, about 90% aorta does not have any atherosclerotic sign, measure the blood plasma of the 3rd group of rabbit and the amino acid concentration of urine week about, intravenous aminoacid quantity delivered was increased to every kg body weight 17 grams and adds glutamic acid and aspartic acid preparation from every kg body weight 1.5 grams every day.The final aminoacid that has provided the preparation that gives the 3rd group of rabbit in the B hurdle of table III is formed.Attention branched-chain amino acid in this composition increases at most, and arginine has increase slightly.Repeat these experiments, up to the result of study of whole 200 rabbits in per three groups all with till The above results is consistent.

This experiment shows, the degeneration without exception of atherosclerotic plaque dirt is to carry out the amino acid-treated result of intravenous separately, and these researchs were for further carrying out patient's experimentation afterwards and lay a good foundation and having avoided fault.

According to chronological order, study this and begin to change the atherosclerosis solution of using the same prescription that injects 40 rabbits of last batch of over to, patient has been experimentized.

Embodiment 2

A patient who suffers from serious familial II type hyperlipidemia Secondary cases systemic atherosclerosis of 40 years old, in the past in a lipid research clinic, be that the method for using the diet that gives low cholesterol/fat, (1400 card) low in calories to be used in combination cholesteric cheese amine is treated, consider now to treat with solution of the present invention.With preceding a kind of method treatment, even the blood plasma cholesterol level of having treated patient after 5 months also can only drop to 409 milligrams/deciliter (the normal plasma cholesterol levels is up to 260) from 496 milligrams/deciliter baseline, and the patient does not feel alleviating of any following symptom.The patient stops after this daily life system in two weeks voluntarily, and its blood plasma cholesterol level is got back to the level of 490-536 milligram/decilitre again.

Patient's myocardial infarction is fully recovered the year before, but this patient still suffers from angina cordis, and it is lame behind the block of only walking serious shank spasm and lower limb just to take place, and often takes place to stick up and numb limbs and tense tendons dusk, and this is relevant with its main artery blood flow poorness.Generally can on arm and lower limb, touch 8 do not hold pulsation have 4 touch less than, all the other pollex intensity of 4 approximately reduce 50%.Coronary angiography shows that the right main total occlusion of coronary artery of atherosclerosis Secondary cases fills the air contraction and blood flow minimizing with left front descending and annular coronary artery.There is not tangible myocardium side Zhi Xunhuan, and because the general diffusion of the state of an illness, he can not carry out the coronary artery bypass surgical operation.

His life expectancy was less than 2 years.Its plasma cholesterol concentration is 540 milligrams/deciliter.He can only walk reluctantly, stick up attack times and the order of severity increase dusk, so he falls down and injured several.Its ventral aorta, iliac artery and carotid magnetic resonance image (MRI) further confirm, the tube chamber of these blood vessels has 80% to be blocked by the atherosclerosis speckle.The doppler ultrasound of two lower limb studies show that the both sides artery blood flow significantly reduces.

A percutaneous central vein conduit is inserted in the superior vena cava by right subclavian vein, has the quiet notes solution that the listed aminoacid in top table III B hurdle is formed for earlier then patient's continuous infusion.The every kg body weight of initial patient is accepted 1.35 gram aminoacid or is just supplied with the aminoacid that patient 95 restrains in the above-mentioned preparation every day.The every kg body weight of patient is also accepted the heat of 35 card glucose forms, with and vitamin, mineral and the trace element of daily requirement, these materials will adopt the intravenous additive of standard.Through six months treatments and clinical research, some basal metabolism data have been obtained gradually.In whole research process, require the patient not take in any food outside dewatering.

The patient being carried out in the process of atherosclerosis infusion treatment and research,, initial solution formula has been carried out repeatedly adjusting according to blood plasma cholesterol level shown in Figure 1.

As seen from Figure 1, plasma cholesterol concentration just dropped to 450 milligrams/deciliter from 508 initial milli Grams Per Minutes within two days.On the 1st, in mixture every day total amount of heat from 2500 cards (35 card/kilogram) reduce to 2100 cards (30 card/kilograms because patient's activity is less, required do not have to estimate at first so high.At the 8th day of treatment, blood plasma cholesterol level further dropped to 370 milligrams/deciliter, but rises to 393 milligrams/deciliter again at the 9th day.On the 2nd, with branched-chain amino acid-lysine, isoleucine and valine-daily dose increase by 2 grams.In this, it is as follows that following aminoacid respectively accounts for the approximate weight percentage ratio of aminoacid gross weight in the mixture: isoleucine: 7.9%; Leucine: 8.9%; Lysine: 5.9%; Methionine: 5.0%; Phenylalanine: 5.9%; Threonine 3.0%; Tryptophan; 2.0%; Valine: 7.9%; Alanine: 14.9%; Arginine: 9.9%; Histidine: 3.0%; Proline: 7.9%; Serine: 5.9%; Tyrosine: 0.4%; Glycine: 5.9%; Glutamic acid: 3.0%; Aspartic acid: 2.0%; Cysteine: 0.6%.The aminoacid consumption of every kg body weight every day is increased to 1.45 from 1.35 grams; The total amount that gives amino acid whose day in the above-mentioned preparation is 101.5 grams.

Within 10 days behind the begin treatment, blood plasma cholesterol level acutely is reduced to 220 milligrams/deciliter, has promptly reduced by 57% from 508 milligrams of/deciliter base levels.On the 3rd point, the 4th and the 5th,, the concentration and the glucose card number of various amino acid compositions changed a little according to the results of biochemical of serum and urine samples.More particularly, on the 3rd, in the amino acid salts of day total supply, increase by 1 restrains phenylalanine and reduces by 1 gram glycine.On the 4th, the quantity delivered that increases glucose every day is to providing 35 card/kilogram heats, because patient's activity increases and the beginning loss of weight.On the 5th, in the aminoacid of total supply every day, alanine has been reduced by 3 grams, and glutamic acid and aspartic acid respectively increase by 1.5 grams.

On the 6th, at 10% of the single 500 milliliters of dosage of quiet notes.Afterwards, blood plasma cholesterol level acutely rises to 370 milligrams/deciliter from 260 milligrams/deciliter to Oleum Glycines Emulsion (selling with registered trade mark Intralipid).The total amount of heat of the 7th and the 8th the expression glucose form of giving reduces to 34 card/kilograms and 33 card/kilograms respectively.Cholesterol in the blood plasma behind the fat infusion Emulsion at least around time dimension be held in and be significantly higher than on the level of carrying out the plasma cholesterol floor level that reaches before the above-mentioned fat transfusion.Keep after the phase, plasma cholesterol rolls back 300 milligrams/deciliter again.On the 4th, after vein is imported 20% Oleum Glycines Emulsion (Intralipid) of single 500 milliliters of dosage, the serum blood plasma cholesterol level rises to 345 milligrams/deciliter, and this further confirms even import essential fatty acid (as Oleum Glycines Emulsion) and also plasma cholesterol is produced illeffects.On the 10th, every day, glucose card number reduced to 30 card/kilograms, and the daily dose of proline and serine respectively reduces by 2 grams.Because the patient feels energy and weight loss, thus on the 11st, with glucose day quantity delivered return to 35 card/kilograms.On the 12nd, the concentration of arginine in solution is almost doubled, reduce the amount of histidine simultaneously.The table IV of plasma cholesterol below 306 milligrams of/deciliter compositions that obviously drop to 245 milligrams of/deciliter ispols in this are listed in.Aminoacid consumption at that point is increased to 1.5 grams from every kg body weight gram every days 1.45, and aminoacid aggregate supply every day is 103.5 grams.

The table IV

Aminoacid weight % mole % aminoacid weight % mole %

Isoleucine 7.7 7.8 alanine 11.6 17.0

Leucine 8.7 8.6 histidine 2.4 1.5

Lysine 5.8 4.2 proline 5.8 6.6

Methionine 4.8 4.3 serines 3.9 4.8

Phenylalanine 6.8 5.3 tyrosine 0.4 0.3

Threonine 2.9 3.2 glycine 4.8 8.4

Tryptophan 1.9 1.3 glutamic acid 4.4 3.9

Valine 7.7 8.6 aspartic acids 3.4 3.3

Arginine 16.4 10.2 cysteine 0.6 0.6

In next week, repeat coronary angiography, the magnetic resonance image (MRI) of patient's aorta, carotid artery and iliac artery, and the research of the doppler ultrasound of two lower limb.Stopped treatment and research then, the patient recovers to take food and contains the diet of cholesterol, every day cholesterol to limit the quantity of be 100 milligrams.

In six months therapeutic process, the patient's angina cordis or the not generation of fainting; Touched in the past less than four terminal pulsations have three can touch now; Four terminal pulsation strength can touching in the past increase 50-100%; Static doppler ultrasound studies show that the blood that flows to shank is stable and is increased to 250-300%, and the patient can with 4 miles speed per hour walk the 3-4 mile every day and the lower limb spasm does not take place or lower limb lame.

Six months the treatment end of term, magnetic resonance image (MRI) showed that ventral aorta, common iliac artery and carotid arterial atherosclerosis speckle dirt reduce 40-50%.Repeat coronary angiography, it is wide clog-free to demonstrate left front descending and belt coronary artery, and the multiple collateral artery that leads to right coronary artery also is wide choke free except the former part of entirely shutting of its originating point.

Except that demonstrating the phenomenon that these miraculous atherosclerotic plaque points disappear and the blood of the in the past impaired multiple tremulous pulse of flowing through increases, show on evidence that also the patient body function is improved.This patient can participate in 18 cave golf range games and beat 18 holes with 70 bars, and the tame building construction company that can be hired by works as the carpenter.Since beginning to receive treatment, he has kept asymptomatic and positive movable more than 15 months.For confirming that achievement that Fadeaway of Atherosclerosis and artery blood flow and body function improve (as mentioned above, this disappear and just improve obviously show on one's body this patient) and proceeded periodically to observe and study, the result shows, this disappear and improve effect be before any medication of utilization and Dietotherapy method institute inaccessiable.

Later on again this patient is carried out during six months the treatment research institute gradually the last solution of formation be infused in other 10 rabbits, these 10 rabbits be with other content all with the part of adding group of 40 rabbits of the identical method research of method as mentioned above.This add the atherosclerosis that confirms in these 10 rabbits of group degenerate in the atherosclerosis of the animal of being studied is degenerated be the most effective, at last make peace the most completely, and atheromatous disappearance rate is 98%-99%.

Embodiment 3

Obtain the other evidence of this method effectiveness by the central vein situation of volunteers that conduit accepted two months to 8 years the full nutrition supply of parenteral of feeding according to 30, and made the atherosclerotic compositions of treatment.Within the week after infusion aqueous (aqueous solution infusate) being changed into the listed amino acid composition of infusion table III or table IV, the blood plasma cholesterol level of all curers, all on the basis of its common cholesterol levels, no matter its order of magnitude has reduced 40%-60%.These discoveries have very high significance, because the order of magnitude that shown blood plasma cholesterol level reduces in these curers is very big, and the positive reaction rate is 100%.The venous transfusion that all these patients accepted before this for a long time, use the ispol that contains conventional TPN substrate to carry out, but blood plasma cholesterol level is without any tangible decline.And the transfusion compositions of table IV can cause blood plasma cholesterol level significantly to reduce.

The described solution of table IV at an outstanding example aspect the cholesterol effect of reduction blood ravine is, within a week, the plasma cholesterol concentration that just makes a patient was from dropping to 50 milligrams/deciliter with regard to 83 milligrams/deciliter not high baseline concentrations originally, and the aqueous solution that this explanation utilization has the listed aminoacid composition of table IV makes plasma cholesterol reduce by 40%.

These data show that mechanism of action of the present invention may be a kind of positive biochemical process, rather than the result of the cholesterol in the strict dietary restriction, cholesterol precursor and other lipid.These data have also proved effect of the present invention.The present composition and method as previously mentioned and described in an embodiment, provide a kind of unique, strong and effective treatment of atherosclerosis method.The last reduction blood cholesterol levels that confirms is carried out, is intended to the lipid research of being undertaken by the AHI's tissue consultation of doctors of finishing recently and the test of coronary heart disease primary prevention to the mankind can reduce the research first of heart attack and heart attack death.Yet although strengthen diet control and take falling the plasma cholesterol medicament, during research in 10 years, the average level of plasma cholesterol has only reduced by 8.6%, and the reduction of reacting best patient's plasma cholesterol is not higher than 19% yet.Yet with common people's faciation ratio, the incidence rate of the myocardial infarction in this seminar has also reduced by 19%.If make blood plasma cholesterol level reduce 40-60%, then the incidence rate of myocardial infarction can also descend more significantly, and adopt the present invention, and is verified as the front, can realize the blood plasma cholesterol level reduction of above-mentioned intensity.

Be noted that many improvement and adjustment beyond the embodiment that can specifically provide in front above-mentioned composition and method, and do not break away from spirit of the present invention.Therefore, should be well understood to, the present invention of Miao Shuing is illustrative in this manual, can not limit scope of the present invention.

Claims (21)

1, a kind of method that reduces blood plasma cholesterol level and the antiatherosclerotic that reverses arterial plaque dirt deposition relevant and vascular wall degeneration situation of preparation with atherosclerosis, this agent contains biological activity aminoacid, and the step of this method comprises:

Isoleucine and the leucine of about 3%-10% weight and the lysine of about 2.5%-7.5% weight and the methionine of about 2.5%-7.5% weight and the phenylalanine of about 3%-10% weight and the threonine of about 1%-4% weight and the tryptophan of about 1%-3% weight and the valine of about 3%-10% weight and the alanine of about 2%-20% weight that (A) will account for about 3%-10% weight of said biologically active amino acid gross weight combine the salt of any crystal form that said amino acid preferably from acetate, chlorination compound salt and hydrochloride select with the aspartic acid of about 0%-6% weight with the cysteine of about 0%-1% weight with the glutamic acid of about 0%-6% weight with the glycine of about 0%-10% weight with the tyrosine of about 0%-1% weight with the serine of about 0%-8% weight with the proline of about 0%-10% weight with the histidine of about 1%-4% weight with the about arginine of 7%-20% weight.

(B) be equilibrated at employed ion in the said salt; And

(C) in medicament, add atoxic organic compound to regulate pH value, make it within the PH of human blood scope.

2, the method for claim 1, wherein said aminoacid combines with following weight:

Account for isoleucine and the leucine of about 5%-10% weight and the lysine of about 4.5%-6.5% weight and the methionine of about 3.5%-5.5% weight and the phenylalanine of about 4.5%-7.5% weight and the threonine of about 2%-3.5% weight and the tryptophan of about 1%-2.5% weight and the about valine of 4%-9% weight of about 4%-10% weight of said biologically active amino acid gross weight, with the glycine of the tyrosine of the alanine of about 7%-16% weight and the arginine of about 9%-18% weight and the histidine of about 1.5%-3.5% weight and the proline of about 4.5%-8.5% weight and the serine of about 2.5%-6.5% weight and about 0%-1% weight and about 3%-8% weight and the glutamic acid of 3.5%-5.5% weight and the aspartic acid of about 2%-4% weight and the about cysteine of 0%-1% weight.

3, claim 1 or 2 method, wherein the arginine amount of Jia Ruing accounts for the percentage by weight maximum of said biological activity aminoacid gross weight.

4, claim 1,2 or 3 method, wherein said biological activity aminoacid contains their anticlockwise form.

5, preparation is a kind of contains active antiatherosclerotic and is used for the treatment of atherosclerotic compositions method, and its step comprises:

(A) with following at least a few seed amino acid isoleucine in the biological activity aminoacid, leucine, valine and arginine combine with effective dosage; And

(B) add non-toxic organic compounds is regulated said compositions within people's blood PH value scope pH value in addition;

Said compositions can be reduced plasma cholesterol content with the form parenterai administration of aqueous solution in the valid period, reverse arterial plaque dirt precipitation and the vascular wall degeneration relevant with atherosclerosis, the weight that arginine is joined in the said compositions is the largest percentage that accounts for said biological activity aminoacid gross weight.

6, the method for claim 5, lysine wherein, methionine, phenylalanine, threonine, tryptophan and histidine further are added in the said compositions and go.

7, claim 5 or 6 method, alanine wherein, proline, serine, tyrosine, glycine, glutamic acid, aspartic acid and cysteine further are added in the compositions and go.

8, claim 5,6 or 7 method, wherein said biological activity aminoacid is the left handed crystal form that is selected from them.

9, the method for claim 7, wherein said aminoacid is added in the said solution with following amount and goes:

Account for the isoleucine of the 3.5%-10% weight of said biological activity aminoacid gross weight greatly, the leucine of 3%-10% weight, the lysine of 2.5%-7.5% weight, the methionine of 2.5%-7.5% weight, the phenylalanine of 3%-10% weight, the threonine of 1%-4% weight, the tryptophan of 1%-3% weight, the valine of 3%-10% weight, the alanine of 2%-20% weight, the arginine of 7%-20% weight, the histidine of 1%-4% weight, the proline of 0%-10% weight, the serine of 0%-8% weight, the tyrosine of 0%-1% weight, the glycine of 0%-10% weight, the glutamic acid of 0%-6% weight, the aspartic acid of 0%-6% weight, the cysteine of 0%-1% weight.

10, the method for claim 9, wherein said aminoacid are that following column weight amount is added in the said solution:

Account for the phenylalanine therewith approximately glycine of the tyrosine of the threonine of 2%-3.5% weight and the tryptophan of about 1%-2.5% weight and the valine of about 4%-9% weight and the alanine of about 7%-16% weight and the arginine of about 9%-18% weight and the histidine of about 1.5%-3.5% weight and the proline of about 4.5%-8.5% weight and the serine of about 2.5%-6.5% weight and about 0%-1% weight and about 3%-8% weight and the glutamic acid of 3.5%-5.5% weight and the aspartic acid of about 2%-4% weight and the about cysteine of 0%-1% weight of isoleucine and the leucine of about 5%-10% weight and the lysine of about 4.5%-6.5% weight and the methionine of about 3.5%-5.5% weight and about 4.5%-7.5% weight of about 4%-10% weight of said biologically active amino acid gross weight.

11, send out among the claim 5-9 method any, its further method comprises and adds the nutritional supplementation composition.

12, a kind of method that is used for the treatment of atherosclerotic aqueous solution of preparation, this disease is characterised in that fatty material is deposited on arteries internal layer and fibrosis, causes speckle dirt deposition concurrent changing property on blood vessel wall.Preparation method comprises and will contain from isoleucine, leucine, the interpolation solution of active amino acid of selecting in valine and the arginine and their mixture joins in the aqueous matrix and regulate the pH value of this solution within people's blood PH value scope, said interpolation solute is effectively measured with one and is joined in the solution, effective dose is represented said solution parenterai administration can be reduced plasma cholesterol content before the deadline, reverses the arterial plaque dirt deposition and reverses the vascular degeneration situation relevant with atherosclerosis.

13, the aqueous solution of claim 12, its further step comprise and add lysine again in aqueous solution, methionine, phenylpropyl alcohol aminoacid, threonine, tryptophan and histidine.

14, the aqueous solution of claim 13, its further step comprise interpolation alanine proline, serine, tyrosine, glycine, glutamic acid, aspartic acid and cysteine in aqueous solution again.

15, claim 12,13 or 14 aqueous solutions, wherein said arginic adding weight is the maximum percentage by weight that accounts for biological activity aminoacid gross weight.

16, any one method among the claim 12-15, wherein said biological activity aminoacid contains their levorotatory form.

17, any one method among the claim 12-15, wherein said biological activity aminoacid comprises their crystal form.

18, any one method among the claim 12-17, wherein said solution contains:

Account for glycine and the glutamic acid of 0%-6% weight and the aspartic acid of about 0%-6% weight and the about cysteine of 0%-1% weight of serine and the tyrosine of about 0%-1% weight and about 0%-10% weight of isoleucine and the leucine of about 3%-10% weight and the lysine of about 2.5%-7.5% weight and the methionine of about 2.5%-7.5% weight and the phenylalanine of about 3%-10% weight and the threonine of about 1%-4% weight and the tryptophan of about 1%-3% weight and the valine of about 3%-10% weight and the alanine of about 2%-20% weight and the arginine of about 7%-20% weight and the histidine of about 1%-4% weight and the proline of about 0%-10% weight and about 0%-8% weight of about 3%-10% weight of said biologically active amino acid gross weight

19, any one method among the claim 12-18, wherein said solution contains:

Account for serine and the tyrosine of about 0%-1% weight and the glycine of about 3%-8% weight and the glutamic acid of about 3.5%-5.5% weight and the aspartic acid of about 2%-4% weight and the about cysteine of 0%-1% weight of isoleucine and the leucine of about 5%-10% weight and the lysine of about 4.5%-6.5% weight and the methionine of about 3.5%-5.5% weight and the phenylalanine of about 4.5%-7.5% weight and the threonine of about 2%-3.5% weight and the tryptophan of about 1%-2.5% weight and the valine of about 4%-9% weight and the alanine of about 7%-16% weight and the arginine of about 9%-18% weight and the histidine of about 1.5%-3.5% weight and the proline of about 4.5%-8.5% weight and about 2.5%-6.5% weight of about 4%-10% weight of said biologically active amino acid gross weight.

20, any one method among the claim 12-19, its further step comprise the nutritional supplementation composition is added to adds in the solute.

21, any one method among the claim 12-20, wherein said solvent comprises disinfectant deionized water substrate.

22, any one method among the claim 12-21, the content concn of wherein said interpolation solute in said water-based are the biological activity aminoacid that contains at least 4 grams in per 100 ml solns, better are to contain the 7.5-12 gram, preferably contain the 9-12 gram.

Images