CN100394924C - Application of high permeability medicine composition in preparing pre-nacrosis medicine - Google Patents
Application of high permeability medicine composition in preparing pre-nacrosis medicine Download PDFInfo
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- CN100394924C CN100394924C CNB2005100299724A CN200510029972A CN100394924C CN 100394924 C CN100394924 C CN 100394924C CN B2005100299724 A CNB2005100299724 A CN B2005100299724A CN 200510029972 A CN200510029972 A CN 200510029972A CN 100394924 C CN100394924 C CN 100394924C
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- sodium chloride
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- 239000003814 drug Substances 0.000 title claims abstract description 27
- 239000000203 mixture Substances 0.000 title claims abstract description 14
- 230000035699 permeability Effects 0.000 title abstract 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 102
- 206010002091 Anaesthesia Diseases 0.000 claims abstract description 61
- 230000037005 anaesthesia Effects 0.000 claims abstract description 61
- 235000002639 sodium chloride Nutrition 0.000 claims abstract description 48
- 239000011780 sodium chloride Substances 0.000 claims abstract description 47
- 229920001612 Hydroxyethyl starch Polymers 0.000 claims abstract description 23
- 238000002347 injection Methods 0.000 claims abstract description 19
- 239000007924 injection Substances 0.000 claims abstract description 19
- 229920000159 gelatin Polymers 0.000 claims abstract description 15
- 235000019322 gelatine Nutrition 0.000 claims abstract description 15
- 229920002472 Starch Polymers 0.000 claims abstract description 13
- 239000008107 starch Substances 0.000 claims abstract description 13
- 235000019698 starch Nutrition 0.000 claims abstract description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims abstract description 10
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims abstract description 10
- 108010010803 Gelatin Proteins 0.000 claims abstract description 9
- 239000008273 gelatin Substances 0.000 claims abstract description 9
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 9
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 9
- 239000000084 colloidal system Substances 0.000 claims abstract description 8
- 229920002307 Dextran Polymers 0.000 claims abstract description 7
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 7
- 239000013078 crystal Substances 0.000 claims abstract description 7
- 229910001415 sodium ion Inorganic materials 0.000 claims abstract description 7
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims abstract description 5
- 239000001110 calcium chloride Substances 0.000 claims abstract description 5
- 229910001628 calcium chloride Inorganic materials 0.000 claims abstract description 5
- 235000011148 calcium chloride Nutrition 0.000 claims abstract description 5
- 239000004227 calcium gluconate Substances 0.000 claims abstract description 5
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- 229960004494 calcium gluconate Drugs 0.000 claims abstract description 5
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 claims abstract description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims abstract description 5
- 235000019341 magnesium sulphate Nutrition 0.000 claims abstract description 5
- 239000001103 potassium chloride Substances 0.000 claims abstract description 5
- 235000011164 potassium chloride Nutrition 0.000 claims abstract description 5
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 55
- 229940027278 hetastarch Drugs 0.000 claims description 22
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 15
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 13
- 239000008103 glucose Substances 0.000 claims description 13
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- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 8
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- 239000001632 sodium acetate Substances 0.000 claims description 8
- 235000017281 sodium acetate Nutrition 0.000 claims description 8
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 7
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- 239000000661 sodium alginate Substances 0.000 claims description 7
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- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000001828 Gelatine Substances 0.000 claims description 6
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 239000001540 sodium lactate Substances 0.000 claims description 6
- 235000011088 sodium lactate Nutrition 0.000 claims description 6
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- 239000005715 Fructose Substances 0.000 claims description 5
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 5
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- 235000010447 xylitol Nutrition 0.000 claims description 5
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 5
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- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 claims description 4
- 239000001527 calcium lactate Substances 0.000 claims description 4
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 3
- 239000003708 ampul Substances 0.000 claims description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 3
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to an application of a high permeability medicine composition before preparing anesthesia medicine. The composition comprises 1.5 to 6.9% (w/v) of crystal selected from one or a plurality of substances of sodium chloride, sodium bicarbonate, potassium chloride, magnesium sulfate, calcium chloride, calcium gluconate, etc., 3 to 18%(w/v) of colloid selected from one or a plurality of substances of hydroxyethyl starch, dextran, carboxymethyl starch, polyvinylpyrrolidone, gelatin derivatives, etc., and conventional injection as the rest, wherein the content of the sodium chloride can not be less than 1.5% (w/v), and the concentration of sodium ions can not exceed that of the sodium ions equivalent to 6.9% (w/v) in the sodium chloride. Before anaesthesia, the high permeability medicine composition is injected as transfusion; the dosage is from 100 to 500 ml/person. After the high permeability medicine composition is used, the disturbance of cardiovascular functions caused by the anaesthesia can be obviously reduced. The high permeability medicine composition has the advantages of safe and convenient usage, quick curative effect, favorable effect, long holding time, etc., and can be widely and previously used for various types of anaesthesia.
Description
Technical field
The present invention relates to the application in the medicine of a kind of high sepage pharmaceutical composition use before preparation anesthesia.
Background technology
Anesthesia is the important component part of medical science, does not have the development of anesthesia, does not just have the development of modern surgery.Just paid attention to very much the effect of anesthesia in Huatuo's epoch.The W.T.G.Morton of Britain odontologist (1819～1868) has at first adopted the ether inhalation anesthesia method in 1846.In the same year, American J.C.Warren (1778～1856) has adopted etherization to do major operation under Morton assists.Along with the progress of science, developed multiple anesthesia later on again.
The purpose of anesthesia is when patient is carried out surgical operation, makes patient's peace and quiet painless, of flaccid muscles, can recover smoothly after the operation.It is very important wherein making patient painless when performing the operation, otherwise anesthesia has just lost meaning.Accomplish the painless pain sensation conduction that then must block patient, in pain sensation conduction block, also blocked other neural conduction, even can have influence on patient's central nervous system.Therefore except the local anesthesia of some minor operations, other anesthesia all have in various degree influence to patient, and general anesthesia such as intravenous anesthesia, to suck anesthesia, combined anesthesia etc. will be more obvious to the influence of patient's cardiovascular system.Shi Yushu (Shi Yushu, Deng Is seals the chief editor, " human recycle system and anesthesiology ", and the 1st edition, Beijing, Chinese Medicine science and technology publishing house publishes 1990) and point out: anesthesia can make ECG change, blood pressure drops (rising), heart pump failure ...Illustrate that not only anesthesia influences blood vessel, heart, blood volume, but also influence electrocardio-activity.Containing tall and erect people (Sheng Zhuoren chief editor, " practical Clinical Anaesthesiology ", the 1st edition, Liaoning, Liaoning science tech publishing house, 1987) thinks: anesthesia can influence central nervous system, breathing, circulation, liver and kidney.Obviously, anaesthetizing general anesthesia especially is comprehensively and significantly to the influence of human body.Wang Yunming (Wang Yunming, China's medical science today, 2003,3 (8): 82) summarized of effect and the influence of anaesthetic propofol to cardiovascular system, the proof propofol has direct inhibitory action to the heart papillary muscles, show as the decline of left ventricular end diastolic presssure and left ventricular filling pressure, cause degradation under myocardial contraction decline and vasodilation (and vein is than the easier expansion of tremulous pulse), the arterial pressure.Wang Yunming points out that simultaneously the prevention propofol prevents the hypotension except giving vaso-excitor material thing such as ephedrine in advance that to the method for cardiovascular system influence other method is the preceding fluid infusion of anesthesia.Because Herba Ephedrae have significant side effects and contraindication, therefore adopting clinically at present and replenishing isotonic solution is method with the most use, but the consumption of isotonic solution is difficult to control, under narcotism, cause tissue edema such as pulmonary edema etc. easily, so (Veroli P et Al. such as Veroli, Br J Anaesth, 1992,69:461) before anesthesia, give 5% sodium chloride solution in advance, though the result shows the amount infused of experimental group and obviously is less than matched group (normal saline and ringer's solution), but the operation in order to keep the ephedrine consumption and the there was no significant difference of mean arterial pressure, they think that it is being feasible aspect the quick liquid make-up of anesthesia that height oozes sodium chloride, and it is also unnecessary to keep the skin wet in a large number.(Scalabrini A et al. such as Scalabrini, Circ Shock, 1992,36 (2): 231) give 7.5% sodium chloride, 5.4% lithium chloride, 50% glucose and 20% mannitol (osmotic pressure of four kinds of high sepages is identical) respectively before bupivacaine anesthesia, the result shows that heavy dose of bupivacaine can cause to quiver in tangible sinus node dysfunction, ventricular arrhythmia, chamber, bradycardia even heart beating stop.Though height oozes the sodium chloride group tachycardia also takes place, routine number reduces, the time shortens, it is dead not have.Quiver etc. in sinus node dysfunction, tachycardia, the chamber that the many cases numbers have but taken place other high sepage groups, and longer duration and with death.Experiment shows that also height oozes the sodium chloride group and can alleviate the reduction of anesthetic stage cardiac index and the reduction of mean arterial pressure.Therefore they think toxicity, the protection heart that sodium ion can the antagonism bupivacaine.Though definite mechanism is also unclear, the high sodium chloride that oozes has obtained preliminary manifesting to the protective effect of anaesthetizing.
Use the concentration that height oozes sodium chloride to concentrate on 7.0%～7.5% over nearly more than 20 years, its main foundation is (Velasco IT et al. such as velasco, Am J Physiol 1980,239 (5): the H664-H673) article of delivering in 1980 is that the experiment of the Concentraton gradient of non-sodium chloride is foundation but velasco etc. admit to use this concentration.Therefore high in the past sodium chloride very significantly complication (Zhao Chaoying etc., PLA's medical journal, 2002,27 (12): 1069-1070 of oozing have deeply been found along with research; Hope booth pine etc., PLA's medical journal, 2003,28 (12): 1102-1103), as the hypotension during the administration, cardiac arrhythmia, tic, obviously support potassium, high sodium, high chlorine, renal failure and high mortality etc., even foreign literature has report to show that height oozes the antishock final effect of sodium chloride not as isotonic solution (Maningas PA et al., Ann Emerg Med, 1986,15 (10): 1131).(Zhao Chaoying etc., The 2nd Army Medical College journal, 1999,20 (11): 918-919 such as Zhao Chaoying; Zhao Chaoying etc., the practical surgical magazine of China, 2000,20 (7): 439--440) further research has been done in high sepage, pointed out the problems of present existence, wherein particularly concentration problems and intravenous injection inject problem (US5443848 and US 4927806) fast.Through deep research, the applicant proposes disclosed high sepage pharmaceutical composition in oneself the Chinese patent (ZL98108902.X), and it is compared with the high sepage of external report, shows very big-difference as follows:
This high sepage pharmaceutical composition and the comprehensively comparison of the high sepage of foreign literature report
This high sepage pharmaceutical composition is the proper ratio that has found under mathematical model between colloid and crystal, thereby can reduce the concentration of sodium chloride, can utilize colloidal characteristic to keep blood volume again, therefore its effect is obviously used sodium chloride above single, also can reduce the generation of toxicity.Therefore this hyperosmotic fluid composition is to have accomplished the safety of medicine and the harmony of effectiveness in treatment.On the basis of Chinese patent (ZL98108902.X), a kind of high sepage " height oozes sodium chloride hetastarch 40 injection " with China's independent intellectual property right is formally produced.The characteristics of being somebody's turn to do " injection " are that safety is big, effective.Use result after clinical trial and the list marketing shows that also shock is had good rescue and therapeutic effect, and does not see tangible toxicity.
Because the height of above-mentioned bibliographical information oozes that sodium chloride uses before anesthesia all only is breadboard research discussion, does not also have so far and can also be to use isotonic solution usually before anaesthetizing clinically at present clinically as the report of drug use before the anesthesia.For this reason, new purposes of the high sepage pharmaceutical composition redevelopment of the application people first.
Summary of the invention
The invention provides a kind of high sepage pharmaceutical composition is that cardiovascular system is protected the application in the medicine at preparation anesthesia previous crops.
When patient carried out surgical operation, anesthesia can influence patient's cardiovascular function, and the effective ways that this influence degree can be alleviated are transfusions.The invention provides a kind of high sepage pharmaceutical composition as the preceding medication infusion that uses of anesthesia, can accomplish the safety of medicine and the harmony of effectiveness.Can obviously reduce anesthesia patient's cardiovascular function disorder, have safe and convenient to use, curative effect is fast, effective, hold time long and can be widely used in various types of anesthesia before advantage such as use.
The action principle of middle and high infiltration liquid pharmaceutical composition of the present invention is to utilize the moisture of its hetero-organization that the osmotic pressure gradient of high sepage will temporarily not play an important role and a matter to be drawn onto to play fluid infusion and expanding blood volume effect in the blood vessel, utilize contained colloid, for example hetastarch is stored in the blood vessel moisture of being drawn to keep blood volume.Therefore the amount of infusion that uses is few, effective.Utilize this action principle that high sepage pharmaceutical composition is not appeared in the newspapers as yet as the preceding medicine that uses of anesthesia.
Among the present invention as a kind of high sepage pharmaceutical composition that uses before the clinical anesthesia, its composition is to comprise that 1.5-6.9% (w/v) crystal is selected from sodium chloride, sodium bicarbonate, potassium chloride, magnesium sulfate, calcium chloride, calcium gluconate, calcium lactate, sodium lactate, one or more materials in sodium acetate and the Tris and 3-18% (w/v) colloid are selected from hetastarch, dextran, carboxymethyl starch, polyvinylpyrrolidone, gelatine derivative, polyglucose, glucose, fructose, lactose, glycerol, xylitol, sodium alginate, N-2-hydroxypropyl acrylamide, oxirane-polypropylene glycol, one or more materials in pectin and the pentahydroxy-ethyl starch, and the routine injection of surplus, condition is that sodium chloride is no less than 1.5% (w/v) in the compositions, and the concentration of sodium ion is no more than the Na ion concentration in the sodium chloride that is equivalent to 6.9% (w/v).
Preferred high sepage pharmaceutical composition is to contain 4.2 ± 0.2 gram sodium chloride and 7.6 ± 0.6 gram hetastarch in per hundred milliliters of liquid.
Wherein:
Having the molecular weight of 10% hetastarch in the described hetastarch at least is 25,000-45,000.
The molecular weight of described dextran is 40,000-230,000; The molecular weight of carboxymethyl starch is 30,000-80,000; The molecular weight of polyvinylpyrrolidone is 5,000-700,000; The molecular weight of polyglucose is 8,000-12,000; The molecular weight of sodium alginate is 20,000-26,000; The molecular weight of pectin is 20,000-40,000; The molecular weight of pentahydroxy-ethyl starch is 264,000.
The molecular weight of described gelatine derivative is 20,000-35, and 000, it is selected from urea interlinkage gelatin, improvement liquid gelatin, oxypolygelatin and degraded gelatin polypeptide.
Described routine is selected from water for injection, normal saline, balance liquid, glucose solution, sodium lactate solution, sodium acetate solution, tris solution and sugar-salt-water with injection.
Described high sepage pharmaceutical composition prepares by following method: 3-18 is restrained colloid be selected from hetastarch, dextran, carboxymethyl starch, polyvinylpyrrolidone, gelatine derivative, polyglucose, glucose, fructose, lactose, glycerol, xylitol, sodium alginate, N-2-hydroxypropyl acrylamide, oxirane-polypropylene glycol, it is 100 milliliters of waters for injection that are selected from conventional injection that one or more materials in pectin and the pentahydroxy-ethyl starch are dissolved in total amount, normal saline, balance liquid, glucose solution, sodium lactate solution, sodium acetate solution, one or more blended liquid in tris solution and the sugar-salt-water solution, add 1.5 gram sodium chloride and 0-5.4 gram crystal again and be selected from sodium chloride, sodium bicarbonate, potassium chloride, magnesium sulfate, calcium chloride, calcium gluconate, calcium lactate, sodium lactate, one or more materials in sodium acetate and the Tris obtain high sepage pharmaceutical composition by said ratio behind mixed dissolution.
High sepage pharmaceutical composition among the present invention is to inject for transfusion at the clinical anesthesia previous crops to use, with the protection patient.Using dosage is to decide according to patient's the state of an illness and body weight, and adult's using dosage generally is 100-500ml/ people, and more people uses 250-500ml/ people.As patient is shock patients, when rescue shock, used this high sepage pharmaceutical composition (referring to Chinese patent ZL98108902.X), the consumption of its rescue can reach 750ml (" height oozes sodium chloride hetastarch 40 injection description " of issuing referring to SFDA), therefore before operation, also can use this high sepage pharmaceutical composition 100ml-500ml, so the total amount of medication can reach about 1250ml.
The use of high sepage pharmaceutical composition described in the present invention is by the medication of instiling in intravenous drip or the bone before anesthesia.Anesthesia administration of anaesthetic routinely after the administration, anesthesia comprises: intramuscular anesthesia, local infiltration anesthesia and regional block anestesia, intravertebral anesthesia (comprising lumbar anesthesia and epidural anesthesia), plexus nervorum block anesthesia, intravenous anesthesia, suction anesthesia, combined anesthesia, acupuncture anesthesia and Chinese drug anesthesia etc.
The packing container that high sepage pharmaceutical composition uses described in the present invention can be plastic bag, plastic bottle, vial, glass ampoule bottles.The loading amount of container can be 50ml, 100ml, 250ml, 370ml or 500ml.Also can install in advance in the described packing container or subsidiary vein (or bone in) injection needle and/or tube for transfusion, pressure apparatus, infusion pump.
The medicine that the induction of anesthesia phase feeds is may be to nervous system inhibited or cardiac muscle had inhibitory action, cause myocardial contraction obviously to reduce, prenarcotic in addition fasting and make blood volume itself be in certain not enough state, therefore vasodilation take place easily cause the relative deficiency of blood volume, blood pressure drops, end-diastolic volume reduce, the oligemia etc. of whenever fighting thereby cause.Normally turn round in order to keep body, so heart rate, vasoconstrictive are accelerated to reach the blood supply that has enough cardiac outputs to come maintenance organization and organ in body reflexive ground, but, finally cause blood pressure obviously to reduce because the effect of anaesthetic has surpassed the reflection or the regulating power of body.The high sepage pharmaceutical composition of the present invention uses for transfusion at the anesthesia previous crops, proves that by animal experiment (seeing embodiment 12) protection of infusing in advance to cardiovascular system is effective.Shown this high sepage pharmaceutical composition of input before anesthesia, except the expanding blood volume effect that utilizes crystal such as sodium chloride, the work that has also utilized colloid such as hetastarch is in order to keep blood volume.Therefore, this high sepage pharmaceutical composition has the effect of transfusion replenishment of blood content, prevent the effect of blood pressure drops in addition, the more important thing is the regulating power that has strengthened cardiovascular system, the disturbance of cardiovascular system is reduced, shows: blood pressure does not have obvious decline, myocardial contraction is normal, cardiac output is normal or increase, no tangible vascular resistance rising; End-diastolic volume reduces, the oligemia of whenever fighting, hypovolemic degree alleviate, and experimental data shows that the effect of high sepage pharmaceutical composition is better than isotonic solution.
In addition, also chamber laboratory examination by experiment of the present invention (seeing embodiment 13) has proved that it is safe using another characteristics of medicine before the high sepage pharmaceutical composition of the present invention is as anesthesia.This high sepage pharmaceutical composition uses back glutamic oxaloacetic transaminase, GOT, renal function all normal.Medicine effect such as hemodilution effect that compositions embodied are very obvious, show: glutamate pyruvate transaminase, total protein, globulin and leukocytic minimizing, significantly low potassium, hypernatremia, hyperchloremia and osmotic pressure obviously raise.All pharmacological actions of laboratory examination caused unusually after 24 hours full recovery normal, illustrate that compositions has reached the effectiveness of medicine and the harmony of safety.
The present invention uses high sepage pharmaceutical composition and prior art to use isotonic solution to compare before anesthesia, has following outstanding characteristics and progress:
1. significantly reduce the consumption of the preceding transfusion liquid of anesthesia: generally speaking, the consumption of most patients is within 250 milliliters or 500 milliliters, and this can obviously reduce tissue edema, the OL incidence rate of cardiac function.
2. curative effect is fast, effective: experimental data shows that the effect of high sepage pharmaceutical composition is better than isotonic solution.
3. the length of holding time: from experimental result as can be known, import high sepage pharmaceutical composition after, even no longer give any other liquid and medicine, after the hematodinamics that is improved can be maintained until induction of anesthesia.
4. use simply, conveniently, can do to instil in intravenous drip or the bone, reduced the generation of complication; Convenient transportation need not the special installation and the special vehicles.
5. need not do blood group and cross matching, any blood group all is suitable for.
6. purposes is wide: before can be widely used in various types of anesthesia.
In sum, medicine was protected patient before the present invention adopted high sepage pharmaceutical composition as anesthesia, with prior art use isotonic solution compare unique beneficial effect and theoretic innovation, have positive effect.
The specific embodiment
Embodiment 1
Prepare by following proportioning:
Hetastarch 7.6 grams
Sodium chloride 4.2 grams
Water for injection is added to 100 milliliters
7.6 gram hetastarch are dissolved in 100 milliliters of waters for injection, add 0.5 gram activated carbon, 90 ℃ of following agitating heating 15 minutes, filter the back and add 4.2 gram sodium chloride (medical pure) stirring and dissolving, add 0.5～1.0 gram activated carbon, 90 ℃ of following agitating heating 10 minutes, more after filtration, by 0.6～0.8 micron microporous filter membrane.The filtrate of gained is filled in glass ampoule bottles, infusion solutions vial or the plastic bottle (bag) of 50 milliliters, 100 milliliters, 250 milliliters, 370 milliliters or 500 milliliters, capping is after 1.05kg/cm
2, 121-123 ℃ sterilization 15-30 minute, promptly obtain high sepage pharmaceutical composition.
Embodiment 2
Prepare by following proportioning:
Hetastarch 8 grams
Sodium chloride 4.1 grams
Normal saline is added to 100 milliliters
8 gram hetastarch, 4.1 gram sodium chloride are dissolved in 100 ml physiological salines, with activated carbon adsorption decolouring, filtration, fill and sterilization, obtain high sepage pharmaceutical composition according to embodiment 1 described method.
Embodiment 3
Prepare by following proportioning:
Sodium chloride 5.1 grams
Glucose solution (18%) is added to 100 milliliters
Above-mentioned sodium chloride is dissolved in glucose solution (18%), stirs the back dissolving, with activated carbon adsorption decolouring, filtration, fill and sterilization, obtain high sepage pharmaceutical composition according to embodiment 1 described method.
Embodiment 4
Prepare by following proportioning:
Hetastarch 6 grams
Gelatin 5 grams
Sodium chloride 5 grams
Water for injection is added to 100 milliliters
Above-mentioned hetastarch, gelatin, sodium chloride are dissolved in water for injection, with activated carbon adsorption decolouring, filtration, fill and sterilization, obtain high sepage pharmaceutical composition according to embodiment 1 described method.
Embodiment 5
Prepare by following proportioning:
Hetastarch 6.5 grams
Sodium chloride 3 grams
Sodium lactate 2 grams
Water for injection is added to 100 milliliters
Above-mentioned hetastarch, sodium chloride, sodium lactate are dissolved in water for injection, with activated carbon adsorption decolouring, filtration, fill and sterilization, obtain high sepage pharmaceutical composition according to embodiment 1 described method.
Embodiment 6
Prepare by following proportioning:
Polyvinylpyrrolidone (Bayer production) 12 grams
Sodium chloride 2 grams
Sodium bicarbonate 4 grams
Water for injection is added to 100 milliliters
Above-mentioned polyvinylpyrrolidone, sodium chloride, sodium bicarbonate are dissolved in water for injection, stir the back dissolving, with activated carbon adsorption decolouring, filtration, fill and sterilization, obtain high sepage pharmaceutical composition according to embodiment 1 described method.
Embodiment 7
Prepare by following proportioning:
Sodium alginate (production of Nanning pharmaceutical factory) 18 grams
Sodium chloride 1.5 grams
Water for injection is added to 100 milliliters
According to embodiment 1 described method above-mentioned prescription is prepared, obtained high sepage pharmaceutical composition.
Embodiment 8
Prepare by following proportioning:
Pectin (production of 185 hospitals of PLA) 3 grams
Sodium chloride 4 grams
Sodium lactate solution (2%) is added to 100 milliliters
According to embodiment 1 described method, pectin is dissolved in sodium lactate solution, add sodium chloride then to molten, stirring, filtration, fill, sterilization, get high sepage pharmaceutical composition.
Embodiment 9
Prepare by following proportioning:
Polyglucose (southwest, Chongqing pharmacy five factories produce) 7 grams
N-2-hydroxypropyl acrylamide 2 grams
Sodium chloride 5.2 grams
Water for injection is added to 100 milliliters
According to the method for embodiment 1, make high sepage pharmaceutical composition according to above-mentioned prescription.
Embodiment 10
Prepare by following proportioning:
Fructose (production of Shanghai reagent two factories) 5 grams
Xylitol (production of Liaoyang Organic Chemical Plant) 4 grams
Sodium chloride 4.8 grams
Water for injection is added to 100 milliliters
According to the method for embodiment 1, make high sepage pharmaceutical composition according to above-mentioned prescription.
Embodiment 11
Prepare by following proportioning:
Glycerol 2 grams
Lactose (production of Shanghai reagent two factories) 5 grams
Sodium chloride 5.3 grams
Water for injection is added to 100 milliliters
According to the method for embodiment 1, make high sepage pharmaceutical composition according to above-mentioned prescription.
Embodiment 12
Zoopery
(1) materials and methods
Animal: select qualified, as far as possible male and female half and half, 1～2 years old beasle dog for use.
The high sepage pharmaceutical composition that medicine: embodiment 1 makes.
Instrument: No. the 2210561st, CF-II type cardiovascular function diagnostic apparatus Shanghai pencil tool (standard) word 2002, Shanghai anti-star biomedical engineering institute company limited is produced.
Method: clear-headed beasle dog artery and vein intubate, make fundamental measurement, comprise cardiac function, biochemistry (potassium, sodium, chlorine, osmotic pressure, hepatic and renal function), routine blood test.The transfusion treated animal feeds test(ing) liquid earlier, enters the induction period of anesthesia then.The dog of induction of anesthesia phase feeds 1. midazolam hydrochloride 0.3mg/kg quiet notes administration in slow 30 seconds respectively by the step of general anesthesia induction; 2. atmosphere quiet notes of Buddhist nun's 1.5 micrograms/kg too; 3. quiet notes of propofol 2.0mg/kg (per 10 seconds administration 40mg); 4. quiet notes of Rocuronium Bromide 0.6mg/kg.Finish after the administration tracheal intubation immediately, artificial ventilation.It is clear-headed to dog to continue to monitor (per 5 minutes record once), recovers to pull out tracheal intubation after the autonomous respiration, pulls out arterio-venous catheter (extracting blood specimen respectively in inducing after finishing 5 minutes, 15 minutes), ligation blood vessel and sew up wound, and dog is steam again and raises.Extracted blood specimen in second day.
(2) experiment grouping (every group of 5 dogs, n=5)
First group (G1): sham operated rats (blank).Do not anaesthetize behind the venous incubation and do not treat, continue to monitor 3 hours.
Second group (G2): model group.Step substep administration by general anesthesia induction behind the venous incubation continues to monitor.
The 3rd group (G3): positive controls.Feed isotonic solution ringer's solution 4ml/kg (injection speed: 0.4ml/kg/min) before the general anesthesia induction.
The 4th group (G4): test group low dose.Feed high sepage pharmaceutical composition 2ml/kg before the general anesthesia induction.Injection speed is with the 3rd group.
The 5th group (G5): dosage in the test group.Feed high sepage pharmaceutical composition 4ml/kg before the general anesthesia induction.Injection speed is with the 3rd group.
The 6th group (G6): test group heavy dose.Feed high sepage pharmaceutical composition 8ml/kg before the general anesthesia induction.Injection speed is with the 3rd group.
Annotate: the administration of this experiment G4～G6 is slow vein and splashes into, and is different from the method for the quick administration of external high sepage (rapid infusion).
(3) date processing
Experimental data adopts mean ± standard deviation (x ± S) expression.Judge with the t check.P≤0.05 is for differing significantly, and P≤0.01 is for differing highly significant.
The result
The body weight of six groups of dogs, the time of pulling out tracheal intubation (beginning to start at from tracheal intubation) are as shown in table 1.
Body weight of six groups of dogs of table 1. and tracheal intubation time
(1) hemodynamic variation
The induction of anesthesia phase is to the obvious effect of cardiovascular function.First group (G1) is owing to give anaesthetic, and be noiseless to the cardiovascular function of animal, so its cardiovascular function do not have obviously change (P＞0.05) in the observation period, as shown in table 2.G3～G6 is at also no change of transfusion phase.And anesthesia all has in various degree influence to animal, respectively narration.
The variation of table 2. experiment blank group dog observation period cardiovascular function
Embodiment 13 lab testings
This tests in just often, checked hepatic and renal function, electrolyte, routine blood test etc. behind the anesthetic intubate in 5 minutes, 15 minutes, 24 hours respectively.Comprising glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, GOT, total protein, albumin, glucose, total bilirubin, creatinine, sodium, potassium, chlorine, blood osmotic pressure, leukocyte, erythrocyte and platelet.Sham operated rats reaches check in 24 hours after the intubate after respectively at intubate at once, and the result shows no obvious abnormalities.This experiment shows that high sepage pharmaceutical composition heavy dose (8ml/kg) is very obvious to the diluting effect of blood, as the glutamate pyruvate transaminase after the administration, total protein, albumin, leukocytic significant change, other causes that significantly low potassium, hypernatremia, hyperchloremia and osmotic pressure obviously raise.Other change does not have special clinical meaning.See Table 23～36.
Table 23 is respectively organized the variation (unit: mmol/L) of glutamate pyruvate transaminase
Annotate: vs is 1. P＜0.05 just often
Table 24. is respectively organized the variation (unit: mmol/L) of glutamic oxaloacetic transaminase, GOT
Table 25. is respectively organized the variation (unit: g/L) of total protein
Annotate: vs is 1. P＜0.05,2. P＜0.01 just often
Table 26. is respectively organized albuminous variation (unit: g/L)
Annotate: vs is 2. P＜0.01 just often
Table 27. is respectively organized the variation (unit: mmol/L) of glucose
Table 28. is respectively organized the variation (unit: umol/L) of creatinine
Table 29. is respectively organized the variation (unit: umol/L) of total bilirubin
Table 30. is respectively organized the variation (unit: mmol/L) of blood potassium
Annotate: vs is 1. P＜0.05 just often
Table 31. is respectively organized the variation (unit: mmol/L) of blood sodium
Annotate: vs is 1. P＜0.05,2. P＜0.01 just often
Table 32. is respectively organized the variation (unit: mmol/L) of blood chlorine
Annotate: vs is 1. P＜0.05,2. P＜0.01 just often
Table 33. is respectively organized the variation (unit: mOsm/L) of blood osmotic pressure
Annotate: vs is 1. P＜0.05,2. P＜0.01 just often
Table 34. respectively organize leukocytic variation (unit :/L)
Annotate: vs is 1. P＜0.05 just often
Table 35. respectively organize erythrocytic variation (unit :/L)
Table 36. respectively organize hematoblastic variation (unit :/L)
Claims (13)
1. one kind high sepage pharmaceutical composition is that cardiovascular system is protected the application in the medicine at preparation anesthesia previous crops; the composition of said composition is to comprise that 1.5-6.9 weight/volume % crystal is selected from sodium chloride; sodium bicarbonate; potassium chloride; magnesium sulfate; calcium chloride; calcium gluconate; calcium lactate; sodium lactate; one or more materials in sodium acetate and the Tris and 3-18 weight/volume % colloid are selected from hetastarch; dextran; carboxymethyl starch; polyvinylpyrrolidone; gelatine derivative; polyglucose; glucose; fructose; lactose; glycerol; xylitol; sodium alginate; N-2 hydroxypropyl acrylamide; oxirane-polypropylene glycol; one or more materials in pectin and the pentahydroxy-ethyl starch; and the routine injection of surplus; condition is that sodium chloride can not be less than 1.5 weight/volume % in the compositions, and the concentration of sodium ion is no more than the Na ion concentration in the sodium chloride that is equivalent to 6.9 weight/volume %.
2. application according to claim 1 is characterized in that containing in per hundred milliliters of liquid of described high sepage pharmaceutical composition 4.2 ± 0.2 gram sodium chloride and 7.6 ± 0.6 gram hetastarch.
3. application according to claim 1 and 2 is characterized in that described routine is selected from water for injection, normal saline, balance liquid, glucose solution, sodium lactate solution, sodium acetate solution, tris solution and sugar-salt-water with injection.
4. application according to claim 1 and 2, it is characterized in that having at least in the wherein said hetastarch molecular weight of 10% hetastarch is 25,000-45,000.
5. application according to claim 1, the molecular weight that it is characterized in that wherein said gelatine derivative is 20,000-35,000, it is selected from urea interlinkage gelatin, improvement liquid gelatin, oxypolygelatin and degraded gelatin polypeptide.
6. application according to claim 1, the molecular weight that it is characterized in that described dextran is 40,000-230,000; The molecular weight of carboxymethyl starch is 30,000-80,000; The molecular weight of polyvinylpyrrolidone is 5,000-700,000; The molecular weight of polyglucose is 8,000-12,000; The molecular weight of sodium alginate is 20,000-26,000; The molecular weight of pectin is 20,000-40,000; The molecular weight of pentahydroxy-ethyl starch is 264,000.
7. application according to claim 1, it is characterized in that described high sepage pharmaceutical composition is to make by following method: 3-18 is restrained colloid be selected from hetastarch, dextran, carboxymethyl starch, polyvinylpyrrolidone, gelatine derivative, polyglucose, glucose, fructose, lactose, glycerol, xylitol, sodium alginate, N-2-hydroxypropyl acrylamide, oxirane-polypropylene glycol, it is 100 milliliters of waters for injection that are selected from conventional injection that one or more materials in pectin and the pentahydroxy-ethyl starch are dissolved in total amount, normal saline, balance liquid, glucose solution, sodium lactate solution, sodium acetate solution, one or more liquid in tris solution and the sugar-salt-water, add 1.5 gram sodium chloride and 0-5.4 gram crystal again and be selected from sodium chloride, sodium bicarbonate, potassium chloride, magnesium sulfate, calcium chloride, calcium gluconate, calcium lactate, sodium lactate, one or more materials in sodium acetate and the Tris, in this ratio preparation, behind mixed dissolution, obtain high sepage pharmaceutical composition.
8. application according to claim 1 and 2 is characterized in that described high sepage pharmaceutical composition is to inject for transfusion at the administration of anaesthetic previous crops.
9. application according to claim 1 and 2 is characterized in that described high sepage pharmaceutical composition adult using dosage is 100-500ml/ people.
10. application according to claim 9 is characterized in that adult's using dosage of described high sepage pharmaceutical composition is 250-500ml/ people.
11. application according to claim 1 and 2 is characterized in that described high sepage pharmaceutical composition is by the medication of instiling in intravenous drip or the bone.
12. application according to claim 1 and 2, the packing container that it is characterized in that described high sepage pharmaceutical composition is plastic bag, plastic bottle, vial or glass ampoule bottles.
13. application according to claim 12 is characterized in that can installing in advance in the packing container of described high sepage pharmaceutical composition or subsidiary vein or intraosseous injection syringe needle and/or tube for transfusion, pressure apparatus, infusion pump.
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| CN102000109B (en) * | 2010-09-30 | 2013-06-05 | 泰山医学院 | Pharmaceutical preparation using hydrogen as therapeutic substance and preparation method thereof |
| CN104644669A (en) * | 2013-11-19 | 2015-05-27 | 北大方正集团有限公司 | Plasma substitute medicine composition used in first aid and preparation method thereof |
| CN112057701A (en) * | 2020-09-04 | 2020-12-11 | 深圳市威浩康医疗器械有限公司 | Comfortable anesthesia auxiliary control system operation method, electronic device and storage medium |
| CN111990972A (en) * | 2020-09-04 | 2020-11-27 | 深圳市威浩康医疗器械有限公司 | System, device and storage medium for determining the point of unconsciousness during induction of anesthesia |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1235833A (en) * | 1998-05-15 | 1999-11-24 | 赵超英 | Novel drug composition for treating and curing and its preparing method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1235833A (en) * | 1998-05-15 | 1999-11-24 | 赵超英 | Novel drug composition for treating and curing and its preparing method |
Non-Patent Citations (2)
| Title |
|---|
| 高渗氯化钠羟乙基淀粉40治疗失血性休克的临床研究. 望亭松等.上海第二医科大学学报，第25卷第3期. 2005 |
| 高渗氯化钠羟乙基淀粉40治疗失血性休克的临床研究. 望亭松等.上海第二医科大学学报，第25卷第3期. 2005 * |
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