CN1209102C - Arginine acetate oral preparation and clinical application thereof - Google Patents
Arginine acetate oral preparation and clinical application thereof Download PDFInfo
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- CN1209102C CN1209102C CN 02133427 CN02133427A CN1209102C CN 1209102 C CN1209102 C CN 1209102C CN 02133427 CN02133427 CN 02133427 CN 02133427 A CN02133427 A CN 02133427A CN 1209102 C CN1209102 C CN 1209102C
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- OZBJWQQAAQSQPL-WCCKRBBISA-N acetic acid;(2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid Chemical compound CC(O)=O.OC(=O)[C@@H](N)CCCN=C(N)N OZBJWQQAAQSQPL-WCCKRBBISA-N 0.000 title claims abstract description 71
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 claims description 19
- 239000004475 Arginine Substances 0.000 claims description 11
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
- 229920001353 Dextrin Polymers 0.000 claims description 6
- 239000004375 Dextrin Substances 0.000 claims description 6
- 229930006000 Sucrose Natural products 0.000 claims description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 6
- 235000019425 dextrin Nutrition 0.000 claims description 6
- 239000008187 granular material Substances 0.000 claims description 6
- 239000005720 sucrose Substances 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 4
- 229960000583 acetic acid Drugs 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 239000012362 glacial acetic acid Substances 0.000 claims description 4
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 4
- 238000006386 neutralization reaction Methods 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000000811 xylitol Substances 0.000 claims description 4
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 4
- 229960002675 xylitol Drugs 0.000 claims description 4
- 235000010447 xylitol Nutrition 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000011347 resin Substances 0.000 claims description 2
- 229920005989 resin Polymers 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- -1 suspensoid Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 22
- 230000036039 immunity Effects 0.000 abstract description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract description 5
- 206010020597 Hyperchloraemia Diseases 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 3
- 208000014674 injury Diseases 0.000 abstract description 3
- 230000000638 stimulation Effects 0.000 abstract description 3
- 230000008733 trauma Effects 0.000 abstract description 3
- 206010028980 Neoplasm Diseases 0.000 abstract description 2
- 230000000857 drug effect Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract 1
- 238000002512 chemotherapy Methods 0.000 abstract 1
- 238000001959 radiotherapy Methods 0.000 abstract 1
- 230000001629 suppression Effects 0.000 abstract 1
- 229960003121 arginine Drugs 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 229960003589 arginine hydrochloride Drugs 0.000 description 9
- 239000013642 negative control Substances 0.000 description 9
- 210000002381 plasma Anatomy 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 239000013641 positive control Substances 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 5
- 230000003399 chemotactic effect Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 229960001614 levamisole Drugs 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 208000010444 Acidosis Diseases 0.000 description 3
- 206010027417 Metabolic acidosis Diseases 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 230000000242 pagocytic effect Effects 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- 206010000059 abdominal discomfort Diseases 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical class CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108090000244 Rat Proteins Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 230000004673 intestinal mucosal barrier function Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
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- 210000002784 stomach Anatomy 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to an arginine acetate oral preparation which belongs to nonspecific immunity enhancement medicine. The arginine acetate oral preparation has the drug effect component of arginine acetate, has a medium acid and alkali degree, has the pH between 6.0 and 7.5, has no chlorine ion acid radical, has no stimulation on the gastrointestinal tract after the oral administration, and has no hyperchloremia after long-term administration. The arginine acetate oral preparation is used as a kind of immunity enhancement medicine, is clinically and mainly used for severe trauma patients, burn patients, patients after major operation and organism immunity function suppression tumor patients after radiotherapy and chemotherapy, and has the advantages of high safety, convenience and good effect.
Description
One, technical field
The invention belongs to medicine, be specifically related to a kind of medicine of nonspecific immunity potentiation.
Two, background technology
Arginine is the necessary aminoacid of a kind of condition, and its energy human body immunity improving function promotes albumen synthetic, reduces catabolism, protects gastrointestinal mucosa, is the focus of present " nutritional drugs Neo-Confucianism " primary study.Discover that arginine can improve the metabolism of burn rat protein, promotes wound healing.The fire victim replenishes arginine through intestinal can alleviate the burn rear intestinal extent of damage, improves immunologic function, shortens the hospital stays.At present both at home and abroad the commercially available arginine that is used for the treatment of the aspect has only two kinds of L one arginine and arginine hydrochloride; But make the preparation of feedstock production pro ore with them, exist following defective: L one arginine alkalescence stronger, pH is 10.5～12.0, oral back stimulates stronger to gastrointestinal, can cause the symptom of stomach discomfort, and long-term extensive application can influence blood pH, and the arginine hydrochloride slant acidity, pH is 4.7～6.2, and the chloride ion content height, reaching 16.5%～17.1%, there is certain stimulation oral back equally to gastrointestinal tract, not only can cause stomach discomfort, and life-time service can cause metabolic acidosis and hyperchloremia.Therefore, domestic do not have L one arginine and arginine hydrochloride oral formulations to go on the market.Through literature search, only arginine hydrochloride and injection thereof have been recorded in Pharmacopeia of Japan the 13rd edition, American Pharmacopeia 23 editions and Chinese Pharmacopoeia version in 2000; Do not see the reported in literature of relevant arginine acetate oral preparation as yet.
Three, summary of the invention
For overcoming above-mentioned defective and plugging a gap, intend preparing a kind of arginine acetate oral preparation at 6.0～7.5 Arginine acetate., as the medicine of nonspecific immunity potentiation with pH.
The technical scheme that adopts is as follows.
A kind of arginine acetate oral preparation contains binding agent and correctives, it is characterized in that also containing arginine acetate, and the weight percent proportioning of each component is: Arginine acetate. 60～90, binding agent 5～20 and correctives 5～20.
Arginine acetate. removes hydrochloric acid with resin from arginine monohydrochloride, the neutralization of reuse glacial acetic acid is produced; Perhaps L one arginine is directly produced with the glacial acetic acid neutralization.
Suitable medicinal adhesive can be chosen any one kind of them from starch, dextrin, carboxymethyl starch sodium or carboxymethyl cellulose.
Suitable medicinal correctives is sucrose and/or xylitol and Fructus Citri tangerinae essence.
Arginine acetate oral preparation of the present invention can be any dosage form in said granule, tablet, capsule, syrup, suspensoid, Emulsion and the powder on the pharmaceutics.
The active ingredient of oral formulations of the present invention is an Arginine acetate., and acid-base value is moderate, and there is not the chloride ion acid group in pH 6.0～7.5, and oral back can not produce stimulation to gastrointestinal tract, does not take for a long time and can produce hyperchloremia.We irritate the gastric hydrochloric acid arginine with 30%III degree body surface burned rabbit and have occurred blood pH, HCO after 7 days
3 -Reduce, the performance of a series of metabolic acidosiss of degradation under the alkaline reserve, the blood plasma chloride ion content also obviously increases simultaneously, and the burn rabbits situation of filling stomach Arginine acetate. is better, tangible metabolic acidosis do not occur, chloride ion content also is starkly lower than the arginine hydrochloride group.Evidence, under the normal situation of hepatic and renal function, it all is safe taking two kinds of arginine salts of acetate and hydrochloride.But patient to severe trauma, burn, major operation or severe infections, because of its hepatic and renal function all is subjected in various degree infringement, body descends to the regulating power of acid-base balance and electrolyte metabolism, orally use arginine hydrochloride this moment obviously is inappropriate, use the oral formulations of Arginine acetate. feedstock production, just can accomplish safety, effective.
Show that by animal pharmacodynamics test this mouthful can promote immunocyte increment and differentiation, improves lymhocyte transformation rate, the enhance immunity cell gulp down have a liking for, the chemotactic function; Improve NK and LAK cytoactive, promote antineoplastic immune; Strengthen humoral immunization, promote immunoglobulin synthetic.Burn man exempts to replenish the 1.2g Arginine acetate. every day through intestinal, and its immunologic function obviously strengthens after 7 days, and the animal dead rate reduces; Product of the present invention also can promote protein in body synthetic, reduces catabolism, promotes wound healing, and the protection gastrointestinal mucosa is safeguarded intestinal mucosal barrier.
Arginine acetate oral preparation of the present invention is a kind of immunostimulant, is mainly used in the downtrod patient of body's immunity behind severe trauma, burn, major operation and the tumour patient chemicotherapy clinically.
For verifying the drug effect of arginine acetate oral preparation of the present invention, we adopt 30% body surface area III degree burn rabbits model, animal is divided into 8 groups at random: the Arginine acetate. test group of arginine hydrochloride (1.2g/kg) matched group, positive drug matched group, negative medicine matched group and 4 various dose, observe arginine to the burn rabbits Immune Effects.Result of the test such as following table:
Table 1 Arginine acetate. is to the influence of burn White Rabbit mortality rate
The survival total number of elements mortality rate of number of elements (%)
Normal control group 880
Arginine hydrochloride matched group 8 10 20.00
Positive drug matched group (levamisole) 8 11 27.27
Negative medicine matched group (tyrosine) 9 14 35.71
Arginine acetate. 2.4g/kg organizes 9 12 25.00
Arginine acetate. 1.2g/kg organizes 9 10 10.00
Arginine acetate. 0.6g/kg organizes 9 10 10.00
Arginine acetate. 0.3g/kg organizes 8 10 20.00
Experimental result shows that 30%III degree burn White Rabbit mortality rate is higher.Arginine hydrochloride, positive drug and negative medicine matched group are respectively 20.00%, 27.27 and 35.71%, 4 dosage groups of Arginine acetate. are 10-25%, wherein the death of 0.6g/kg and 1.2g/k Arginine acetate. group is 10%, is starkly lower than other group (P＜0.01).
Table 2 Arginine acetate. is to the influence of burn White Rabbit lymhocyte transformation rate, leukocytes phagocytic rate and chemotactic index
Drench rate of rotation (%) phagocytic rate (%) chemotactic index
Normal control group (n=8) 68.38 ± 5.07 36.75 ± 2.82 1.95 ± 0.25
Arginine hydrochloride group (n=8) 52.50 ± 4.87
* △32.13 ± 3.14
* △1.89 ± 0.18
△
△
Positive controls (levamisole) (n=8) 56.88 ± 5.01
* △29.88 ± 2.85
* △1.61 ± 0.23
*
△
△
Negative control group (tyrosine) (n=9) 48.00 ± 3.09
* ##22.33 ± 3.50
* ##1.61 ± 0.15
*
Arginine acetate. 2.4g/kg organizes (n=9) 55.22 ± 5.41
* △ △30.89 ± 3.38
The * Δ1.92 ± 0.22
△ △ ##
△
Arginine acetate. 1.2g/kg organizes (n=9) 58.44 ± 4.90
* △ △30.56 ± 2.95
* △1.92 ± 0.33
△ △ ##
△
Arginine acetate. 0.6g/kg organizes (n=9) 46.89 ± 4.18
* ##27.11 ± 4.01
*1.60 ± 0.21
*
Arginine acetate. 0.3g/kg organizes (n=8) 46.25 ± 4.35
* ##19.88 ± 3.10
* ##1.51 ± 0.14
*
*Compare P＜0.01 with normal group; △ △ and negative control group be P＜0.01 relatively; ## and positive controls be P＜0.01 relatively
Burn after 7 days, above-mentioned three indexs of each treated animal all are starkly lower than normal group (P＜0.01).In 4 dosage groups of Arginine acetate., 1.2g/kg and pouring rate of rotation, phagocytic rate and the chemotactic index of 2.4g/kg group are all apparently higher than negative medicine matched group, wherein chemotactic index is significantly higher than the positive drug matched group, compares no significant difference with the arginine hydrochloride matched group.0.6g/kg, 0.3g/kg group relatively do not have significant difference (P＞0.05) with negative medicine matched group.The result shows: burn back lymphocyte function descends, and Arginine acetate. can promote lymphocyte function to recover.
Table 3 Arginine acetate. is to the influence of lymphocyte subtype
CD
3(％) CD
4(％) CD
8(％) CD
4/CD
8
Normal control group (n=8) 65.13 ± 5.51 36.75 ± 3.03 24.25 ± 1.64 1.52 ± 0.08
Arginine hydrochloride group (n=8) 51.50 ± 2.18
*30.63 ± 2.91
*23.13 ± 1.62 1.33 ± 0.17
△
△
Positive controls (levamisole) (n=8) 50.38 ± 5.02
*28.63 ± 3.16
*22.00 ± 2.12 1.31 ± 0.17
Negative control group (tyrosine) (n=9) 41.78 ± 2.82
*22.22 ± 2.70
*21.89 ± 1.91 1.02 ± 0.11
*
Arginine acetate. 2.4g/kg organizes (n=9) 52.33 ± 5.85
*30.67 ± 3.78
△ △22.33 ± 1.49 1.37 ± 0.13
△
△
△
Arginine acetate. 1.2g/kg organizes (n=9) 52.33 ± 3.94
*33.78 ± 2.86
△23.78 ± 1.54 1.42 ± 0.10
△
△
△
△
Arginine acetate. 0.6g/kg organizes (n=9) 46.44 ± 4.35
*27.22 ± 3.74
*23.22 ± 2.20 1.17 ± 0.10
*
Arginine acetate. 0.3g/kg organizes (n=8) 44.50 ± 3.12
*23.38 ± 1.93
*22.13 ± 1.62 1.06 ± 0.12
*
*Compare P＜0.05 with normal group,
*Compare P＜0.01 with normal group; △ and negative control group be P＜0.05 relatively, and △ △ and negative control group be P＜0.01 relatively
Burn after 7 days lymphocyte subtype quantity generation significant change, wherein CD
3, CD
4Content and CD
4/ CD
8Ratio all significantly descends, CD
8Changes of contents is not obvious.In 4 groups of Arginine acetate. treatment, the CD of 2.4g/kg and 1.2g/kg group
3, CD
4, CD
4/ CD
8(P＜0.05-0.01), a little more than the positive drug matched group, but differ not remarkable (P＞0.05) compares no significant difference with the arginine hydrochloride group to be significantly higher than negative medicine matched group.And 0.6g/kg and 0.3g/kg group relatively differ not significantly (P＞0.05) with negative medicine matched group.The result shows: Arginine acetate. can effectively be safeguarded the stable of lymphocyte subtype, helps hindering the recovery of back immunologic function.
Table 4 Arginine acetate. is to the influence of burn White Rabbit blood plasma immunoglobulin content
IgA(g/L) IgM(g/L) IgG(g/L)
Normal control group (n=8) 2.36 ± 0.50 1.35 ± 0.14 11.75 ± 3.12
Arginine hydrochloride group 1.74 ± 0.35 1.22 ± 0.29
△ △8.31 ± 1.47
△ △
(n＝8)
Positive controls (levamisole) (n=8) 1.72 ± 0.20 1.14 ± 0.28
△ △8.32 ± 2.16
Negative control group (tyrosine) (n=9) 1.72 ± 0.37 0.61 ± 0.14
*5.51 ± 1.53
*
Arginine acetate. 2.4g/kg organizes (n=9) 1.69 ± 0.26 1.15 ± 0.22
△ △8.37 ± 1.78
△ △
Arginine acetate. 1.2g/kg organizes (n=9) 1.75 ± 0.33 1.26 ± 0.21
△ △8.61 ± 1.25
△ △
Arginine acetate. 0.6g/kg organizes (n=9) 1.56 ± 0.43
*0.91 ± 0.26
* #7.00 ± 0.93
*
Arginine acetate. 0.3g/kg organizes (n=8) 1.78 ± 0.29 0.78 ± 0.31
* ##6.59 ± 0.55
* ##
*Compare P＜0.01 with normal group; △ △ and negative control group be P＜0.01 relatively; ## and positive controls be P＜0.01 relatively
Hindering back 7 days each treated animal blood plasma immunoglobulin IgA, IgM, IgG all has decline in various degree, and wherein the variation of IgG and IgM is comparatively obvious, and the variation of IgA is not obvious.The IgG of Arginine acetate. 2.4g/kg and 1.2g/kg group and IgM relatively do not have significant difference apparently higher than negative medicine matched group (P＜0.01) with arginine hydrochloride group and positive drug group.And 0.6g/kg compares variation not obvious (P＞0.05) with the 0.3g/kg group with negative medicine group.The result shows: provide every day the 1.2-2.4g/kg Arginine acetate. to improve and hinder the back immunoglobulin level, safeguard normal body's immunity.
Table 5 Arginine acetate. is to burn White Rabbit blood plasma interleukin-2 and effect of nitric oxide
Interleukin II (ng/ml) content of nitric oxide (μ mol/L)
Normal control group (n=8) 9.05 ± 2.17 6.14 ± 1.55
Arginine hydrochloride group (n=8) 6.23 ± 1.43
* △ △9.12 ± 3.06
Positive controls (levamisole) (n=8) 5.14 ± 1.16
* △ △8.76 ± 3.51
*
Negative control group (tyrosine) (n=9) 3.22 ± 0.82
*7.55 ± 2.66
Arginine acetate. 2.4g/kg organizes (n=9) 7.18 ± 2.46
△ △ ##14.09 ± 3.09
* △ △ ##
Arginine acetate. 1.2g/kg organizes (n=9) 6.96 ± 1.33
* △ △ ##9.41 ± 2.34
*
Arginine acetate. 0.6g/kg organizes (n=9) 4.31 ± 1.07
*6.58 ± 1.70
Arginine acetate. 0.3g/kg organizes (n=8) 4.03 ± 1.12
*6.68 ± 1.22
*Compare P＜0.01 with normal group; △ △ and negative control group be P＜0.01 relatively; ## and positive controls be P＜0.01 relatively
Burning, each treated animal plasma IL-2 content obviously descends after 7 days, and NO content is then in rising trend.Arginine acetate. 2.4g/kg and 1.2g/kg organize plasma IL-2 content apparently higher than positive and negative medicine matched group (P＜0.01), compare with the arginine hydrochloride group and differ nonsignificance, and 0.6g/kg, 0.3g/kg group changes not remarkable.In arginic 4 dosage groups, the plasma nitric oxide levels of 2.4g/kg group is apparently higher than other several groups.The result shows: take in 1.2g/kg～2.4g/kg Arginine acetate. every day and can improve plasma IL-2 and NO content, promote the lymphocytic emiocytosis function, safeguard body's immunity.
The optimum effective dose of the arginine acetate oral preparation that the present invention relates to is 1.2g/kg.d.This dosage safety is effective.
Four. the specific embodiment
The particulate preparation of example 1 Arginine acetate.
Prescription
Arginine acetate. 2500g
Sucrose 300g
Dextrin 177g
Xylitol 20.0g
Flavoring orange essence is an amount of
Make 1000 bags
Preparation technology: take by weighing Arginine acetate., sucrose, dextrin mix homogeneously by formula ratio,, adopt the equivalent mixing method mix homogeneously that progressively increases, pulverize, cross 80 mesh sieves again with the xylitol of mixed powder and recipe quantity; Make uniform soft material, granulate by 16 mesh sieves.Drying below 60 ℃ 4 hours is received powder, sprays into an amount of flavoring orange essence, and with 14 mesh sieve granulate, censorship is up to the standards, packing, and packing is promptly.
The preparation of example 2 Arginine acetate. capsules
Prescription
Arginine acetate. 400g
Dextrin 50g
Sucrose 50g
Make 1000
Preparation technology: take by weighing Arginine acetate., sucrose, dextrin mix homogeneously by formula ratio, pulverize, cross 80 mesh sieves; Make uniform soft material, granulate by 16 mesh sieves.Drying below 60 ℃ 4 hours is received powder, and with 14 mesh sieve granulate, censorship is up to the standards, in pack into hard capsule or the enteric coated capsule.
Claims (5)
1, a kind of arginine acetate oral preparation contains binding agent and correctives, it is characterized in that also containing Arginine acetate., and the weight percent proportioning of each component is: Arginine acetate. 60～90, binding agent 5～20 and correctives 5～20.
2, according to the arginine acetate oral preparation of claim 1, it is characterized in that said Arginine acetate. removes hydrochloric acid with resin from arginine monohydrochloride, the neutralization of reuse glacial acetic acid is produced; Perhaps L one arginine is directly produced with the glacial acetic acid neutralization.
3, according to the arginine acetate oral preparation of claim 1, it is characterized in that said binding agent, from starch, dextrin, carboxymethyl starch sodium or carboxymethyl cellulose, choose any one kind of them.
4, according to the arginine acetate oral preparation of claim 1, it is characterized in that said correctives is sucrose, xylitol and Fructus Citri tangerinae essence, optional wherein one or both.
5,, it is characterized in that dosage form is any dosage form in said granule, tablet, capsule, syrup, suspensoid, Emulsion or the powder on the pharmaceutics according to the arginine acetate oral preparation of claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02133427 CN1209102C (en) | 2002-07-05 | 2002-07-05 | Arginine acetate oral preparation and clinical application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02133427 CN1209102C (en) | 2002-07-05 | 2002-07-05 | Arginine acetate oral preparation and clinical application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1465341A CN1465341A (en) | 2004-01-07 |
| CN1209102C true CN1209102C (en) | 2005-07-06 |
Family
ID=34145559
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02133427 Expired - Fee Related CN1209102C (en) | 2002-07-05 | 2002-07-05 | Arginine acetate oral preparation and clinical application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1209102C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106619565B (en) * | 2016-10-28 | 2020-02-14 | 广州中大南沙科技创新产业园有限公司 | Arginine preparation, and preparation method and application thereof |
-
2002
- 2002-07-05 CN CN 02133427 patent/CN1209102C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1465341A (en) | 2004-01-07 |
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