CN1083704A - 治疗hiv血清阳性个体的药品 - Google Patents
治疗hiv血清阳性个体的药品 Download PDFInfo
- Publication number
- CN1083704A CN1083704A CN93104081A CN93104081A CN1083704A CN 1083704 A CN1083704 A CN 1083704A CN 93104081 A CN93104081 A CN 93104081A CN 93104081 A CN93104081 A CN 93104081A CN 1083704 A CN1083704 A CN 1083704A
- Authority
- CN
- China
- Prior art keywords
- medicine
- whey protein
- protein concentrate
- application
- undenatured whey
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 208000007521 HIV Seropositivity Diseases 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 title claims description 15
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims abstract description 42
- 229960003180 glutathione Drugs 0.000 claims abstract description 37
- 102000004407 Lactalbumin Human genes 0.000 claims abstract description 32
- 108090000942 Lactalbumin Proteins 0.000 claims abstract description 32
- 239000012141 concentrate Substances 0.000 claims abstract description 32
- 210000004027 cell Anatomy 0.000 claims abstract description 15
- 230000037396 body weight Effects 0.000 claims abstract description 11
- 210000004369 blood Anatomy 0.000 claims abstract description 10
- 239000008280 blood Substances 0.000 claims abstract description 10
- 210000005087 mononuclear cell Anatomy 0.000 claims abstract description 4
- 230000003862 health status Effects 0.000 claims abstract description 3
- 108010071390 Serum Albumin Proteins 0.000 claims description 16
- 102000007562 Serum Albumin Human genes 0.000 claims description 16
- 108060003951 Immunoglobulin Proteins 0.000 claims description 14
- 102000007544 Whey Proteins Human genes 0.000 claims description 14
- 108010046377 Whey Proteins Proteins 0.000 claims description 14
- 102000018358 immunoglobulin Human genes 0.000 claims description 14
- 235000021119 whey protein Nutrition 0.000 claims description 14
- 230000003203 everyday effect Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 108010024636 Glutathione Proteins 0.000 claims description 3
- 102000008192 Lactoglobulins Human genes 0.000 claims description 3
- 108010060630 Lactoglobulins Proteins 0.000 claims description 3
- 229940072221 immunoglobulins Drugs 0.000 claims description 3
- 235000021241 α-lactalbumin Nutrition 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 235000003969 glutathione Nutrition 0.000 abstract description 31
- 238000000034 method Methods 0.000 description 15
- 235000013336 milk Nutrition 0.000 description 14
- 239000008267 milk Substances 0.000 description 14
- 210000004080 milk Anatomy 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 230000007850 degeneration Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- PABVKUJVLNMOJP-WHFBIAKZSA-N Glu-Cys Chemical group OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(O)=O PABVKUJVLNMOJP-WHFBIAKZSA-N 0.000 description 7
- 229940027941 immunoglobulin g Drugs 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 235000013305 food Nutrition 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 4
- 239000005018 casein Substances 0.000 description 4
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 4
- 235000021240 caseins Nutrition 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 230000035764 nutrition Effects 0.000 description 4
- 238000009928 pasteurization Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 235000021245 dietary protein Nutrition 0.000 description 3
- 238000001471 micro-filtration Methods 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 108010000912 Egg Proteins Proteins 0.000 description 2
- 102000002322 Egg Proteins Human genes 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- DWEYIZCNGQAQTF-DKWTVANSSA-N L-cysteine-glycine Chemical compound NCC(O)=O.SC[C@H](N)C(O)=O DWEYIZCNGQAQTF-DKWTVANSSA-N 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 210000003677 hemocyte Anatomy 0.000 description 2
- 229940000351 hemocyte Drugs 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 229940099472 immunoglobulin a Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 230000000527 lymphocytic effect Effects 0.000 description 2
- 210000004681 ovum Anatomy 0.000 description 2
- 230000004792 oxidative damage Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000620196 Arthrospira maxima Species 0.000 description 1
- 240000002900 Arthrospira platensis Species 0.000 description 1
- 235000016425 Arthrospira platensis Nutrition 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000195649 Chlorella <Chlorellales> Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010036164 Glutathione synthase Proteins 0.000 description 1
- 102100034294 Glutathione synthetase Human genes 0.000 description 1
- 101100438957 Mus musculus Cd8a gene Proteins 0.000 description 1
- 108010064983 Ovomucin Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000195663 Scenedesmus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- SIHBHANPKGAGGC-DFWYDOINSA-N [SH2]=N.N[C@@H](CCS)C(=O)O Chemical compound [SH2]=N.N[C@@H](CCS)C(=O)O SIHBHANPKGAGGC-DFWYDOINSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000011681 asexual reproduction Effects 0.000 description 1
- 238000013465 asexual reproduction Methods 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- OHJMTUPIZMNBFR-UHFFFAOYSA-N biuret Chemical compound NC(=O)NC(N)=O OHJMTUPIZMNBFR-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 244000144987 brood Species 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000021268 hot food Nutrition 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000036417 physical growth Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 229940108461 rennet Drugs 0.000 description 1
- 108010058314 rennet Proteins 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940082787 spirulina Drugs 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/19—Dairy proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/20—Milk; Whey; Colostrum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Developmental Biology & Embryology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Polymers & Plastics (AREA)
- Marine Sciences & Fisheries (AREA)
- Nutrition Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
将未变性的乳清蛋白浓缩物对HIV-血清阳性
个体给药,以提高他们的血液单核细胞,谷胱甘肽
(GSH)水平,体重和健康状况。另外,个体的T-助
细胞浓度和个体的T-助细胞/T-抑制细胞比例也
有少量的提高。
Description
本发明涉及治疗HIV血清阳性个体的药品,具体地说,涉及用于治疗HIV血清阳性个体的乳清蛋白浓缩物药品。
在本说明书的最后给出12篇参考文章,其内容都可作为本文的参考。
我们的研究表明,喂以20g乳清蛋白浓缩物/100g食物的小鼠的体液免疫应答(对绵羊红血细胞产生形成噬菌斑细胞数目)比喂以类似营养效能的含20g/100g食物的任何其它市售半纯化食物蛋白(如酪蛋白,大豆,小麦,玉米,蛋清,鱼,牛蛋白,最大螺旋藻(Spirulina maxima)蛋白,绿藻(Scenedesmus algae)蛋白,或Purina鼠料等)的小鼠有明显提高[1]。
我们进一步研究表明,喂食乳清蛋白的动物在淋巴细胞的需氧抗原驱动的无性增殖过程中,喂食乳清蛋白浓缩物(WPC)的免疫增强活性与脾的谷胱甘肽的较高产生有关[2]。这可能反映出食用乳清蛋白食物的小鼠的淋巴细胞有补偿潜在的氧化损伤的能力,因此,有更强的抗原抵抗能力[3,4]。事实上,细胞恢复氧化损伤的能力可以由它再生细胞内存谷胱甘肽的能力来表示[5]。
我们的研究还表明,给喂食乳清蛋白的小鼠服用S-(正丁基)高半胱氨酸磺酰亚胺(该化合物可以将脾的谷胱甘肽降低一半)将明显降低它的体液免疫应答。这进一步证实了谷胱甘肽在食用乳清蛋白的免疫增强活性中的重要作用[2]。
服用γ-谷氨酰基-半胱氨酸可以增加组织谷胱甘肽的浓度。给小鼠皮下(S.C)注射40-60分钟后,其肾赃的谷胱甘肽的浓度增加约50%,并且在2小时后又回到对照组的值[6]。服用的γ-谷氨酰基半胱氨酸以完整的分子在体内输送,并用作谷胱甘肽合成酶的底物[7]。
食物蛋白质的氨基酸序列的进展使我们可以研究在乳清蛋白中有谷氨酰基半胱氨酸基团的存在,并能研究它与谷胱甘肽促进作用的关系。事实上,从牛奶中得到的乳清蛋白浓缩物中含有大量的谷氨酰基半胱氨酸基团,与酪蛋白不同,当喂以小鼠酪蛋白并不能增如组织谷胱甘肽的量[1]。谷氨酰基半胱氨酸基团主要位于血清白蛋白部分中(每分子六个基团)。谷氨酰基半胱氨酸基团在动物和植物的可食用蛋白中含量极少。对可食用蛋白的氨基酸序列的有关资料进行广泛的研究表明,由二硫键连接的甘氨酸-半胱氨酸基团只局限于某些乳清蛋白,而蛋清的卵类粘蛋白部分中,每一个30,000分子量大小的分子中只含有2个这样的基团[8]。
我们最近的实验数据还表明[8],小鼠在喂食高溶解度(非变性型)的食用乳清蛋白浓缩物时有最高的体液免疫应答,特别是含有较高相对浓度的不耐热的牛血清白蛋白(≥10%)和免疫球蛋白的情况下。另外,食用这种类型的乳清蛋白浓缩物的小鼠具有较高水平的组织谷胱甘肽。在血清蛋白部分中存在的谷氨酰基半胱氨酸基团(在食物蛋白中的量很少),以及非变性分子构象中的特定分子内键是蛋白质混和物的谷胱甘肽促进活性的关键因素。
日本的最近实验表明[9],BALB/C雄鼠喂食我们的非变性乳清蛋白浓缩物(WPC,我们称为免疫卡尔“Immunocal”),每100/g该食物中含25gWPC,共喂4星期,其脾细胞在体外对SRBC的免疫应答比对照组鼠有增加,并且含有较多的L3T4+细胞(12.58×106±0.50),对照组小鼠喂食等热食物25g酪蛋白/100g食物(3.69×106±0.50)。类似地,喂食非变性WPC的小鼠的脾L3T4+/LYt-2+比例为1.36±0.07,而喂食酪蛋白的对照组为0.55±0.07(P<0.001)。
在实施例中所用的乳清蛋白浓缩物均是非变性的,它是由很不严格方法处理的牛奶制备得到的,但都能达到细菌污染的安全标准。非常高的溶解度指标表明这种蛋白质基本上是非变性的,所以超滤过程中有很好的穿透性[8]。虽然其它市售的浓缩物中所含有的蛋白质通常也大都是非变性的,比如浓缩物有较高的溶解度等,但是,
这些混合物中所含的血清白蛋白和免疫球蛋白的量明显低于产生有效的生物活性所必需的量[8]。当用高的巴氏灭菌温度处理时,这些非常不耐热的蛋白质会发生变性而沉淀出来,部分从乳清中损失。相反地,我们的WPC由牛奶的低温巴氏灭菌处理制得,含有较高浓度的热敏感血清白蛋白和免疫球蛋白,它可以反映出更接近原牛奶的特性。这些数据支持这样假设:即不耐热的含有甘氨酸-半胱氨酸的蛋白质(如非变性构形的血清白蛋白)是乳清蛋白浓缩物的生物活性的关键因素。
牛乳清蛋白浓缩物是用St-Hyacinthe,Quebec,Canada一书“Service de recherche sur les aliments du Ministere de 1′agriculture du Quebec”中所描述的方法制备,具有如下特点:纯蛋白含量75%(其余的主要是乳糖,一些脂肪和水分);溶解度指数:(ph 4.6);99.5%。通过聚丙酰胺凝胶电泳测得的蛋白质组成(以总的乳清蛋白的%计)[8]为:β-乳球蛋白59.1±4.0;α-乳清蛋白6.6±0.7;血清白蛋白9.7±1.0;免疫球蛋白24.6±2.6(平均值±标准差)。溶解度指数最好应当高于99%。
血清白蛋白的含量约是乳清蛋白总量的10%,几乎是已检测的其它市售乳清蛋白浓缩物的2倍。可以认为,血清白蛋白的量≥10%将非常有利于改进免疫系统。
血清白蛋白含有大量的谷氨酰基半胱氨酸,它是体内谷胱甘肽合成的一个基质。谷胱甘肽的作用已在“未变性食用乳清蛋白的生物活性:谷胱甘肽的作用”(Clin.Invest.Med.14:296-309,1991)一文中作了详细讨论,文中的全部内容都可作为本文的参考。
免疫球蛋白的含量范围在乳清蛋白总量的约25-30%时也是非常重要的。72℃进行巴氏灭菌13秒,使免疫球蛋白的含量是28±2%。我们发现将牛奶在72℃巴氏灭菌13秒可以使血清白蛋白的含量达到14±1%。
细菌学分析表明,无论是用“Sevice de recherche sur les Aliments due Ministere de 1′agriculture du Quebec”方法制备的WPC,还是在72℃进行13秒巴氏灭菌的样品,都未检出葡萄球菌、沙门氏菌、B仙人掌或大肠杆菌等。
图1用图示法描述了制备本发明实施例中所用WPC的方法。
用30ml肝素化的血液来测定血液中单核细胞中谷胱甘肽的含量。将已计数的单核细胞悬浮在磷酸盐缓冲的盐水中,调至每管含有107个细胞。离心后加入900μl水至沉淀中,使细胞全都溶解。向每份中加入30%的磺基水杨酸至终浓度为每1ml含有3%。保温15分钟后,离心样品,上清液按照Anderson[11]的方法进行生化试验。所测值以纳摩尔(nMol)GSH(谷胱甘肽)/107细胞表示。血液淋巴细胞亚群可由流式细胞光度术测得。
血清蛋白总量,包括白蛋白和免疫球蛋白可以用Biuret方法测得。免疫球蛋白A(IgA),免疫球蛋白G(IgG)和免疫球蛋白M(IgM)可由免疫比浊法测定。
在血液中有两个重要的淋巴细胞亚群;(1)CD4,也叫做T-助细胞,因为它们有助于免疫应答;(2)CD8,也叫做T-抑制细胞,因为它们起相反的作用,也就是它们抑制免疫应答。在HIV-血清阳性的个体中,CD4细胞数量少,也就是说,CD4/CD8的比例下降。
本发明的目的就是提高T助细胞对T抑制细胞的比例。这一目的可以通过服用未变性的乳清蛋白浓缩物来实现。
服用剂量应当在每天8-40克的范围内,最好是每天20-40克。对谷胱甘肽量特别有利的剂量是每天服用30-40克。而谷胱甘肽量的提高有利于免疫系统,这在美国专利申请号No.563,794(1990年8月3日呈递)中有更完善的描述,可作为本文的参考。
实施例1
选择3个HIV-血清阳性的男性患者服用上文中所述的乳清蛋白有浓缩物,在表2中分别标记为A、B和C。该产品每天冷冲服,冲服用液体可由患者自选。另外还包括第四个患者D,但是他只是偶尔服用WPC,没有任何规律,并且在研究的最后几天没有服用。因此,他在表2中被列为对照。其它的对照体还有E和F。
WPC的日服入量是逐步增加的。在第一个三周期间每日服用8.4克,第二个三周内每日19.6克,第三个三周内每日28克,最后三周内每日服用39.2克。
观察结果列在下面表2中:
表2乳清
患者 服用乳清 能量 理想 体重 CD4% 助细胞 CD4 GSH 血清蛋白百分率
名称 星期数 (千卡) 体重 (kg) (2) 绝对值 CD8 n mol-102细胞 Alb IgG IgA IgM
(年龄) 蛋白(g) (kg) (3) (4) (5) 总量
(1)
- 0 2180 86 102.5 23 368 0.38 9.75 77 42 20.8 1.54 1.14
87
A 6 1800 105 26 546 0.45 10.34 74 39 19.4 1.56 1.16
106
(35)
12 2111 108 24 480 0.41 13.9 80 42 20.1 1.61 1.05
100
0 1870 75.2 73.9 15 435 0.22 10.22 82 50 12.3 4.38 0.75
84
B 6 2035 74.5 19 532 0.28 9.6 79 45 14.3 4.53 0.76
140
(32)
12 2100 76 17 442 0.24 17.04 72 50 16.9 5.81 0.95
138
0 2400 78 76 24 672 0.39 10.38 82 52 12.4 3.59 0.76
100
C 6 2200 77.5 27 864 0.46 12.55 81 49 12.9 3.99 0.58
116
(20) 12 1400 78 26 676 0.45 7.06 80 50 12.8 3.8 0.7
98
表2(续)
对照
患者 能量 理想 体重 CD4% 助细胞 CD4 GSH 血清蛋白百分率
名称 星期数 (千卡) 体重 (kg) (2) 绝对值 CD8 n mol-102细胞 Alb IgG IgA IgM
(年龄) 蛋白(g) (kg) (3) (4) (5) 总量
(1)
0 2940 95.5 27 540 0.47 12.36 75 47 15.6 1.63 1.34
107
6 2500 85 25 650 0.42 8.59 73 42 15 1.5 1.19
118
0 2500 70 69.5 17 420 10.3 81 44
98
E 6 2600 68.5 21 371 11 82 44
130
(38)
12 2480 68 18 359 9.8 81 44
108
0 2200 74 74 16 263 11.08 80 43
108
F 6 2100 73 12 222 10.3 83 43
120
(37) 12 2300 72 12.5 230 9 80 42
110
1-列出的所摄入的能量及蛋白量代表前几星期的平均值
2-正常范围:35-55
3-正常范围:580-1250
4-正常范围:1.42-3.56
5-GSH:单核血细胞中的谷胱甘肽量。相当年龄的健康的HIV血清阴性个体的正常值范围:17.05±2.40 (平均值±SD)
在表2中:
CD4%表示CD4(助细胞)占血液中淋巴细胞总量的百分率。
助细胞绝对值表示每单位血液中CD4的实际数量[x103每微升(μl)]。
CD4/CD8表示血液中两种淋巴细胞型的比例,即T-助细胞和T-抑制细胞的比例。
总量表示血清中的蛋白总量,包括白蛋白和免疫球蛋白。
IgA表示免疫球蛋白A
IgG表示免疫球蛋白G
IgM表示免疫球蛋白M
表2给出的数据及实验过程中得到的其它的信息具有下列含意。
三个患者每天服用未变性的WPC三个月后,未观察到任何有害的副作用。所有这些患者的体重都逐渐增加(2-7千克);并且有两个(B和C)达到了理想体重。血清蛋白(包括白蛋白)保持不变,并在正常范围之内,这说明蛋白补充本身并不是体重增加的原因。
在所有的这三个患者中,在研究中血液T-助细胞的浓度和T-助细胞/抑制细胞的比例都适中地、但一致地高于服用未变性WPC前时的值。
正象所预料的那样[10],在研究开始时所有患者的血液单核细胞中谷胱甘肽的含量都低于正常值。但是,经过三个月后,谷胱甘肽的水平都有增加,并且有一例(B)增加70%,从而达到正常值。
在文献[10]的1297页中提出了没有症状的HIV-血清阳性个体的系统性谷胱甘肽缺乏使谷胱甘肽正常的细胞外浓度的恢复成为尚未解决的难题。因为静脉注射的谷胱甘肽的半衰期只有1-6分钟。但是,根据本发明的方法,通过服用未变性的WPC可以解决这一难题。
在所有这三个患者中,这些症状的变化都伴随着健康状况的明显改善。
值得注意的是,有一位患者过分担心体重的有益增加会妨碍其苗条外形,他在第三个研究阶段中急剧减少能量和未变性WPC的摄入量(C,表2)。在这时期内,体重的增加降低,并且谷胱甘肽和T-助细胞也不再增加。
正象早期指出的那样,患者D由于对实验方案缺乏认识,而作为对照体,他在第6周末表现出体重、T-助细胞/T-抑制细胞比例及谷胱甘肽量的下降,并且在预定的12周内没有上升趋势。其它的两个对照体(E和F)的体重下降,谷胱甘肽水平没有变化。
这些实例表明,如果患者基本上保持其能量摄入量在研究前的水平上而对上述WPC的摄入量只有少量降低,则在服用WPC期间,他的体重增加,并且特定的HIV指标(如,血细胞谷胱甘肽、T-助细胞浓度、T-助细胞/T-抑制细胞比例)都有适当的提高。
如果结合在大量动物通过服用我们的WPC后表现出细胞谷胱甘肽和免疫应答增加[1,2,8,9]的实验基础上一起考虑,则在这很有限的HIV-血清阳性患者中所观察到的未变性WPC的正疗效,是具有很大的价值的。动物研究强调的事实是未变性WPC的免疫增强效应与较大的系统性营养效能无关,因为其它几个具有相似营养效能的蛋白源都没有明显的生物活性。喂食未变性WPC的小鼠的身体生长并没有增加,血清蛋白水平也没有变化。类似地,在我们的患者中,未变性WPC在血清蛋白中没有产生任何变化,整个研究过程中血清蛋白的量保持不变。在研究过程中所观察到的患者体重的增加与能量或蛋白摄入量的增加没有关联,但与身体健康状况的改善和HIV特定的血液参数有关。通过未变性的WPC所摄入的多余蛋白通常通过降低其它来源蛋白的摄入量来抵偿。
认为在乳清蛋白浓缩物的血清蛋白组分中存在有谷氨酰基半胱氨酸基团是未变性WPC蛋白混合物的谷胱甘肽促进活性和免疫增强活性的关键因素。我们实验室的研究表明,其它来源的乳清蛋白浓缩物不能产生明显的生物活性,但具有类似的营养效能。这些产品中的血清白蛋白的百分浓度(平均值±标准差)分别是:Promod(Ross实验室),4±1; Alacen 855(新西兰乳品店),4±;Lacprodan-80(1989年由Danmark蛋白生产)4.8±;Sapra(Saputo,蒙特利尔),4.8±0.1;Savorpro-75(Golden Cheese,CA),4±1;Bioisolate(Lesueur Isolates,明尼那波利斯)[8],5±1;Promix(Dumex,魁北克),4.3±1。类似地,其它的不耐热蛋白含量,免疫球蛋白,大约是本发明所用的未变性WPC中含量的一半。
这些结果表明,未变性乳清蛋白通过为在免疫细胞补充谷胱甘肽提供特定燃料,可以作为其它治疗形式的辅助剂。
在历史上,并直到现在,通过加热处理(巴氏灭菌)来降低牛奶中的细菌和芽胞。为了有效灭菌,这种方法不可避免地会产变性,从而使大部分最不耐热并推测有生物活性的血清白蛋白和免疫球蛋白以凝乳形式沉淀而损失。
我们的目的就是得到一种乳清蛋白浓缩物(W.P.C),它尽可能地含有与原料奶相近的蛋白组成比例和构形,并且细菌含量达到允许的安全标准。为了保持不耐热的乳清蛋白,到目前为止我们已采用了最低的可允许的热处理牛奶。今后我们将采用一种基于膜微过滤的新方法达到这一目的。
选用Bactocatch(Alfa-Laval Ltd.scarborough,Ontario(安大略)),我们将脱脂奶经过特殊的膜微过滤后,所得透滤液的细菌含量已降低至不足原水平的0.5%。
然后将这种透滤液用粗制凝乳酶处理,乳清上清液中的蛋白质经过浓缩后即可得到所需的未变性乳清蛋白浓缩物。我们相信膜微过滤原理取代加热方法处理牛奶在将来将提供一个合适的途径来保持不耐热的乳清蛋白,虽然在技术和设备方面可以随后改进。
参考文献
1.Bounous G,Kongshavn PAL,Gold P:食用乳清蛋白浓缩物的免疫增强性质,Clin.Invest.Med.11:271-8,1988.
2.Bounous G,Batist G,Gold P:食用乳清蛋白在小鼠中的免疫增强性质:谷胱甘肽的作用,Clin.Invest.Med.12:154-61,1989.
3.Fidelus RK,Tsan MF:细胞内谷胱甘肽的增强促进分裂素对淋巴细胞的活化,Cell.Immunol.97:155-63,1986.
4.Gougerot-Pocidalo MA,Fay M,Roche S:氧化性损伤抑制人淋巴细胞对植物凝集素的增殖反应的机理,巯基化合物2-巯基乙醇的作用。Immunology 64:281-8,1988.
5.Noelle RJ,Laurence DA:淋巴细胞中谷胱甘肽的测定及氧化还原状态与淋巴细胞增殖能力的可能关系。Biochem.J.198:571-9,1981.
6.Anderson ME,Meister A:在谷胱甘肽合成过程中γ-谷氨酰基半胱氨酸的转运和直接利用,Proc.Natl.Acad.Sci.,80:707-11,1983.
7.Meister A:5-羟脯氨酸尿和其它的谷胱甘肽生物合成的紊乱。在:Stranbury JB,Wymgaarden JB,Frederikson DS,著,遗传性疾病的代谢基础(第四版)(Metabolic basis of inherited diseases 4th edn.),McGraw Hill,1978:328-35.
8.Bounous G,Gold P:未变性食用乳清蛋白的生物活性:谷胱甘肽的作用。Clin.Invest.Med.14:296-309,1991.
9.Hirai Y,Nakay S,kikuishi H,Kawai K:报告:免疫卡尔(Immunocal)的免疫增强活性的评价。Otsuka药物有限公司:细胞技术研究所:1990年12月13日,日本大阪(Osaka,Japan)。
10.Buhl R,Holroyd KJ,Mastrangeli A,Cantin AM,Jaffe HA,Wells C,Saltini C,Crytal RG:无症状HIV-血清阳性个体的系统性谷胱甘肽缺乏,Lancet(December 2):1294-7,1989.
11.Anderson ME:组织谷胱甘肽:在:C.R.C Handbook of methods for oxygen radical research(氧自由基研究的方法手册)。Boca Raton,Florida:CRC Press,Inc,1985:317-29.
Claims (18)
1、一种用于治疗HIV-血清阳性个体的药品,包括未变性乳清蛋白浓缩物。
2、权利要求1的药品,包括药物上可接受的载体或赋形剂。
3、权利要求1的药品,其中该未变性乳清蛋白浓缩物的溶解度指数(pH4.6)大于99%。
4、权利要求1的药品,其中未变性乳清蛋白浓缩物的蛋白组成含有:β-乳球蛋白59.1±4.0,α-乳清蛋白6.6±0.7,血清白蛋白9.7±1.0,免疫球蛋白24.6±2.6。
5、权利要求1的药品,其中未变性乳清蛋白浓缩物的日服量范围是约每天8-40克。
6、权利要求5的药品,其中日服量范围是约20-40克。
7、权利要求6的药品,其中日服量范围是约30-40克。
8、权利要求3的药品,其中未变性的乳清蛋白浓缩物中血清白蛋白的含量大于或约等于10%。
9、权利要求8的药品,其中未变性乳清蛋白浓缩物中免疫球蛋白的含量范围是约25-30%。
10、未变性乳清蛋白浓缩物在治疗HIV-血清阳性个体药品中的应用,其使用量要足以提高血液单核细胞中谷胱甘肽含量和体重,并且改善健康状况。
11、未变性乳清蛋白浓缩物在治疗HIV-血清阳性个体药品中的应用,其使用量要足以提高个体的T-助细胞浓度和个体的T-助细胞/T-抑制细胞比例。
12、权利要求11的应用,其中该未变性乳清蛋白浓缩物的溶解度指数(pH4.6)大于99%。
13、权利要求11的应用,其中未变性乳清蛋白浓缩物的蛋白组成含有:β-乳球蛋白59.1±4.0,α-乳清蛋白6.6±0.7,血清白蛋白9.7±1.0,免疫球蛋白24.6±2.6.。
14、权利要求11的应用,其中未变性乳清蛋白浓缩物的日服量范围是约每天8-40克。
15、权利要求14的应用,其中日服量范围是约20-40克。
16、权利要求15的应用,其中日服量范围是约30-40克。
17、权利要求12的应用,其中未变性的乳清蛋白浓缩物中血清白蛋白的含量大于或约等于10%。
18、权利要求17的应用,其中未变性乳清蛋白浓缩物中免疫球蛋白的含量范围是约25-30%。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/866,756 US5456924A (en) | 1988-12-23 | 1992-04-10 | Method of treatment of HIV-seropositive individuals with dietary whey proteins |
US866,756 | 1992-04-10 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1083704A true CN1083704A (zh) | 1994-03-16 |
CN1070371C CN1070371C (zh) | 2001-09-05 |
Family
ID=25348339
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN93104081A Expired - Lifetime CN1070371C (zh) | 1992-04-10 | 1993-04-09 | 治疗hiv血清阳性个体的药品 |
Country Status (19)
Country | Link |
---|---|
US (1) | US5456924A (zh) |
EP (1) | EP0634934B1 (zh) |
JP (1) | JP2738592B2 (zh) |
KR (1) | KR100297959B1 (zh) |
CN (1) | CN1070371C (zh) |
AT (1) | ATE187335T1 (zh) |
AU (1) | AU687731B2 (zh) |
CA (1) | CA2090186C (zh) |
CZ (1) | CZ283386B6 (zh) |
DE (1) | DE69327236T2 (zh) |
DK (1) | DK0634934T3 (zh) |
ES (1) | ES2143503T3 (zh) |
IL (1) | IL105339A (zh) |
MX (1) | MX9302057A (zh) |
NO (1) | NO317795B1 (zh) |
NZ (1) | NZ251271A (zh) |
TW (1) | TW384223B (zh) |
WO (1) | WO1993020831A1 (zh) |
ZA (1) | ZA932526B (zh) |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5531989A (en) | 1994-10-28 | 1996-07-02 | Metagenics, Inc. | Immunoglobulin and fiber-containing composition for human gastrointestinal health |
US6241983B1 (en) | 1994-10-28 | 2001-06-05 | Metagenics, Inc. | Bacteria-and fiber-containing composition for human gastrointestinal health |
US5985275A (en) * | 1995-04-12 | 1999-11-16 | New York Blood Center | β-Lactoglobulin modified with aromatic anhydride compound for preventing HIV infection |
CA2165937A1 (en) * | 1995-05-09 | 1996-11-10 | Immunotec Research Corporation Ltd. | Process for producing an undenatured whey protein concentrate |
WO1997032483A1 (en) * | 1996-03-06 | 1997-09-12 | I. Belloch Corporation | Method for treating liquid materials |
AU1707197A (en) * | 1996-03-20 | 1997-10-10 | New York Blood Center, Inc., The | Methods of treating herpes or chlamydia |
US5952009A (en) * | 1996-03-20 | 1999-09-14 | New York Blood Center | Methods for preventing the transmission of or treating patients infected with herpesvirus |
US6262019B1 (en) | 1998-04-30 | 2001-07-17 | Vit-Immune, L. C. | Method of treatment of glutathione deficient mammals |
US6667063B2 (en) | 1998-06-10 | 2003-12-23 | Albert Crum | Nutritional or therapeutic supplement and method |
ATE322275T1 (de) * | 1998-06-10 | 2006-04-15 | Albert B Crum | Vorbeugender und therapeutischer nahrungsmittelzusatz zur schaffung/erhaltung einer die gesundheit schützenden darmmikroflora und zur stärkung des immunsystems |
US6203805B1 (en) | 1998-11-10 | 2001-03-20 | Color Access, Inc. | Topical compositions containing whey proteins |
US6864242B2 (en) | 2001-03-05 | 2005-03-08 | Stephen P. Ernest | Enteral formulation |
US6503506B1 (en) * | 2001-08-10 | 2003-01-07 | Millenium Biotechnologies, Inc. | Nutrient therapy for immuno-compromised patients |
ES2451618T3 (es) | 2001-12-20 | 2014-03-28 | Biolactis Inc. | Matriz de proteína maleable y usos de estas |
FR2840318B1 (fr) * | 2002-05-29 | 2004-12-03 | Quoc Kiet Pham | Nouveaux sulfolipides antiretroviraux extraits de spirulines, leur procede d'obtention, les compositions les contenant et leur utilisation comme inhibiteurs de la transcriptase inverse des virus vih |
FR2889067B1 (fr) * | 2005-07-29 | 2011-11-11 | Cie Laitiere Europeenne | "utilisation d'une fraction proteique laitiere pour preparer une composition amincissante et/ou ameliorant la composition corporelle" |
DE102006052504A1 (de) | 2006-11-06 | 2008-05-08 | Temper, Rupert | Verfahren zum Herstellen eines Mittels gegen eine Infektionskrankheit |
US20080119386A1 (en) * | 2006-11-22 | 2008-05-22 | Carl Germano | Nutritional formula for athletes' recovery |
AP2009004963A0 (en) * | 2007-02-06 | 2009-10-31 | Cymcorp Internat Inc | Novel non-toxic composition and method of using such for treating a degenerative or an immune systemrelated disease |
US20100069288A1 (en) * | 2008-09-12 | 2010-03-18 | Wulf Droge | Use of cysteine-rich whey derived protein in patients receiving chemotherapy or radiotherapy to improve patient survival |
JP2013079216A (ja) * | 2011-10-04 | 2013-05-02 | Snow Brand Milk Products Co Ltd | 感覚改善剤 |
JP6234777B2 (ja) * | 2013-10-31 | 2017-11-22 | 株式会社日立製作所 | 光多値送信器および光トランスポンダ |
DE102014001037A1 (de) * | 2014-01-25 | 2015-07-30 | Gea Tds Gmbh | Verfahren und Vorrichtung zur Reduzierung des Wachstums thermophiler Keime in Magermilch |
US20190262401A1 (en) | 2016-09-23 | 2019-08-29 | Immunotec Inc. | Compositions for restoring gene expression in neuropsychiatric or neurodegenerative disorders |
CA2970699A1 (en) | 2017-06-14 | 2018-12-14 | Elizabeth E. Ignowski | Compositions for increasing resilience to traumatic brain injury |
WO2019027974A1 (en) | 2017-07-31 | 2019-02-07 | Immunotec Inc. | COMPOSITIONS AND METHODS FOR TREATING AUTISM SPECTRUM DISORDER |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA858533A (en) * | 1970-12-15 | Lahav Eitan | Polypeptidic antibiotic substances derived from casein by fermentation | |
FR2565985B1 (fr) * | 1984-06-19 | 1987-09-25 | Rhone Poulenc Sante | Nouvelles substances biologiquement actives obtenues a partir de la caseine bovine, leur procede de preparation et les compositions qui les contiennent |
US4880626A (en) * | 1985-01-18 | 1989-11-14 | Mcmichael John | Immunotherapeutic methods and compositions for the treatment of diseases of viral origin, including acquired immune deficiency syndrome |
US4983387A (en) * | 1986-05-19 | 1991-01-08 | Viral Technologies Inc. | HIV related peptides, immunogenic antigens, and use therefor as subunit vaccine for AIDS virus |
US5030449A (en) * | 1988-07-21 | 1991-07-09 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Synthetic vaccine against AIDS virus |
EP0338229B1 (de) * | 1988-04-19 | 1993-06-16 | Biotest Pharma Gmbh | Präparat mit Antikörperaktivität und breitem Wirkungsspektrum, daraus bestehende oder diese enthaltende Mittel und deren Verwendung zur Behandlung von bakteriell oder toxin-bedingten Erkrankungen und zur Bekämpfung von Protozoen |
FI892006A (fi) * | 1988-04-29 | 1989-10-30 | Phil Gold | Lactalbumin saosom tillaeggsaemne i mat. |
CA1338682C (en) * | 1988-12-23 | 1996-10-29 | Gustavo Bounous | Biologically active undenatured whey protein concentrate as food supplement |
CA2007258A1 (en) * | 1989-01-11 | 1990-07-11 | Richard L. Jackson | Heparin fraction with anti-hiv activity |
ATE108335T1 (de) * | 1989-03-03 | 1994-07-15 | Microgenesys Inc | Kit oder zusammensetzung zur vorbeugung oder behandlung von hiv-1 infektionen. |
EP0432249B1 (en) * | 1989-06-02 | 1996-09-25 | The Johns Hopkins University School Of Medicine | Monoclonal antibodies against leukocyte adhesion receptor beta-chain, methods of producing these antibodies and use therefore |
CA2022394A1 (en) * | 1989-08-07 | 1991-02-08 | Allen I. Oliff | Peptide inhibitors of human papilloma virus protein binding to retinoblastoma gene proteins |
ATE366311T1 (de) * | 1989-12-22 | 2007-07-15 | Hoffmann La Roche | Zytotoxischer lymphozyten-reifefaktor 35kd untereinheit und monoklonale antikörper spezifisch dafür |
US5112373A (en) * | 1991-06-17 | 1992-05-12 | Hung Pham | Apparatus for controlling and eliminating vapor emissions at a manicure work station |
-
1992
- 1992-04-10 US US07/866,756 patent/US5456924A/en not_active Expired - Lifetime
-
1993
- 1993-02-23 CA CA002090186A patent/CA2090186C/en not_active Expired - Lifetime
- 1993-03-22 DE DE69327236T patent/DE69327236T2/de not_active Expired - Lifetime
- 1993-03-22 JP JP5517869A patent/JP2738592B2/ja not_active Expired - Lifetime
- 1993-03-22 ES ES93907682T patent/ES2143503T3/es not_active Expired - Lifetime
- 1993-03-22 DK DK93907682T patent/DK0634934T3/da active
- 1993-03-22 NZ NZ251271A patent/NZ251271A/en unknown
- 1993-03-22 KR KR1019940703473A patent/KR100297959B1/ko not_active IP Right Cessation
- 1993-03-22 EP EP93907682A patent/EP0634934B1/en not_active Expired - Lifetime
- 1993-03-22 WO PCT/CA1993/000107 patent/WO1993020831A1/en active IP Right Grant
- 1993-03-22 AT AT93907682T patent/ATE187335T1/de active
- 1993-03-22 AU AU38812/93A patent/AU687731B2/en not_active Expired
- 1993-03-22 CZ CZ942461A patent/CZ283386B6/cs not_active IP Right Cessation
- 1993-04-07 MX MX9302057A patent/MX9302057A/es unknown
- 1993-04-08 IL IL10533993A patent/IL105339A/en not_active IP Right Cessation
- 1993-04-08 ZA ZA932526A patent/ZA932526B/xx unknown
- 1993-04-09 CN CN93104081A patent/CN1070371C/zh not_active Expired - Lifetime
- 1993-04-09 TW TW082102661A patent/TW384223B/zh not_active IP Right Cessation
-
1994
- 1994-10-07 NO NO19943804A patent/NO317795B1/no not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
JPH07504677A (ja) | 1995-05-25 |
CZ283386B6 (cs) | 1998-04-15 |
CA2090186C (en) | 1999-03-16 |
ATE187335T1 (de) | 1999-12-15 |
NZ251271A (en) | 1998-05-27 |
MX9302057A (es) | 1994-07-29 |
DE69327236D1 (de) | 2000-01-13 |
ZA932526B (en) | 1994-03-09 |
WO1993020831A1 (en) | 1993-10-28 |
DK0634934T3 (da) | 2000-06-13 |
CZ246194A3 (en) | 1995-04-12 |
CN1070371C (zh) | 2001-09-05 |
CA2090186A1 (en) | 1993-10-11 |
JP2738592B2 (ja) | 1998-04-08 |
ES2143503T3 (es) | 2000-05-16 |
AU3881293A (en) | 1993-11-18 |
IL105339A0 (en) | 1993-08-18 |
IL105339A (en) | 1998-07-15 |
EP0634934B1 (en) | 1999-12-08 |
AU687731B2 (en) | 1998-03-05 |
US5456924A (en) | 1995-10-10 |
TW384223B (en) | 2000-03-11 |
EP0634934A1 (en) | 1995-01-25 |
NO943804D0 (no) | 1994-10-07 |
DE69327236T2 (de) | 2000-03-30 |
KR950700752A (ko) | 1995-02-20 |
KR100297959B1 (ko) | 2001-10-24 |
NO943804L (no) | 1994-10-07 |
NO317795B1 (no) | 2004-12-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1070371C (zh) | 治疗hiv血清阳性个体的药品 | |
Bagath et al. | The impact of heat stress on the immune system in dairy cattle: A review | |
Baruchel et al. | Whey proteins as a food supplement in HIV-seropositive individuals | |
Kelleher et al. | Immunological activities associated with milk | |
Jaiswal et al. | Recent perspective on cow’s milk allergy and dairy nutrition | |
Bocci | Roles of interferon produced in physiological conditions. A speculative review. | |
CN1044660A (zh) | 生物学活性乳清蛋白质组合物,其生产方法及该组合物的应用 | |
Salman et al. | The role of dietary selenium in bovine mammary gland health and immune function | |
CZ114999A3 (cs) | Kolostrinin a jeho použití | |
FR2537436A1 (fr) | Procede de regulation de l'appetit et de l'efficacite de l'utilisation des aliments utilisant de l'interferon | |
Linehan et al. | Bovine colostrum for veterinary and human health applications: A critical review | |
CN1529618A (zh) | 耐受性诱导 | |
CN1260248C (zh) | 从牦牛奶中提取的活性乳蛋白及其方法和应用 | |
Carroll | Bidirectional communication: growth and immunity in domestic livestock | |
JPS6240251A (ja) | 子豚用飼料 | |
JPH0838047A (ja) | 健康食品 | |
Mushtaq et al. | Immunomodulatory effect of levamisole therapy in pre-parturient dairy cows | |
US20170056497A1 (en) | Method of Treating Protozoal Gastrointestinal Disorders in Immunocompromised Patients | |
RU2340352C2 (ru) | Способ коррекции биологической активности молока и применение имунофана и амиксина для такой коррекции | |
Bounous et al. | Whey proteins as a food supplement in EŒV-seropositive individuals | |
Gougerot-Pocidalo | Bounous et al. | |
CN117981831A (zh) | 一种抗高原反应的功能性固体饮料及其制备方法 | |
Crowley | Development of an immunoglobulin-fortified milk replacer and a purified, injectable immunoglobulin solution as alternative methods of achieving passive immunity in colostrum-deprived neonatal calves | |
JP2010065010A (ja) | 胃炎、胃潰瘍および/または十二指腸潰瘍の予防および/または治療用組成物、ならびにそれを含有する飲食品 | |
Matsumoto et al. | Treatment with recombinant IL-2 for recurrent respiratory infection in a case of cartilage-hair hypoplasia with autoimmune hemolytic anemia |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C17 | Cessation of patent right | ||
CX01 | Expiry of patent term |
Expiration termination date: 20130409 Granted publication date: 20010905 |