WO2019128099A1 - Application of diallyl disulfide in preparing drug for treating and/or preventing hyperlipemia - Google Patents
Application of diallyl disulfide in preparing drug for treating and/or preventing hyperlipemia Download PDFInfo
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- WO2019128099A1 WO2019128099A1 PCT/CN2018/089164 CN2018089164W WO2019128099A1 WO 2019128099 A1 WO2019128099 A1 WO 2019128099A1 CN 2018089164 W CN2018089164 W CN 2018089164W WO 2019128099 A1 WO2019128099 A1 WO 2019128099A1
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- diallyl disulfide
- hyperlipidemia
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- PFRGXCVKLLPLIP-UHFFFAOYSA-N diallyl disulfide Chemical compound C=CCSSCC=C PFRGXCVKLLPLIP-UHFFFAOYSA-N 0.000 title claims abstract description 75
- 239000003814 drug Substances 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 title claims abstract description 12
- 201000005577 familial hyperlipidemia Diseases 0.000 title abstract 3
- 235000013376 functional food Nutrition 0.000 claims abstract description 7
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 230000000055 hyoplipidemic effect Effects 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 2
- 239000001095 magnesium carbonate Substances 0.000 claims description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 229940100688 oral solution Drugs 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000000454 talc Substances 0.000 claims description 2
- 229910052623 talc Inorganic materials 0.000 claims description 2
- 210000002966 serum Anatomy 0.000 abstract description 14
- 210000004369 blood Anatomy 0.000 abstract description 11
- 239000008280 blood Substances 0.000 abstract description 11
- 150000002632 lipids Chemical class 0.000 abstract description 8
- 108010023302 HDL Cholesterol Proteins 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 4
- 108010028554 LDL Cholesterol Proteins 0.000 abstract description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 12
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 12
- 238000011156 evaluation Methods 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 238000010171 animal model Methods 0.000 description 7
- 240000002234 Allium sativum Species 0.000 description 4
- UBAXRAHSPKWNCX-UHFFFAOYSA-N diallyl trisulfide Chemical compound C=CCSSSCC=C UBAXRAHSPKWNCX-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000004611 garlic Nutrition 0.000 description 4
- 230000037396 body weight Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000003064 anti-oxidating effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000010647 garlic oil Substances 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241001669134 Heraeus Species 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 206010039020 Rhabdomyolysis Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 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 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000026758 coronary atherosclerosis Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940126673 western medicines Drugs 0.000 description 1
Classifications
-
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/105—Persulfides
-
- 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
Definitions
- the invention belongs to the field of medicine, and particularly relates to the application of diallyl disulfide in the preparation of a medicament for preventing and/or treating hyperlipidemia.
- Hyperlipidemia is a systemic disease in which one or more plasmas of plasma are higher than the normal range due to abnormal fat transport or metabolism. Generally it is total cholesterol (TC) and/or triglyceride (TG). Hyperlipidemia causes diseases that are seriously harmful to human health, especially cardiovascular and cerebrovascular diseases such as coronary heart disease and atherosclerosis.
- TC total cholesterol
- TG triglyceride
- Hyperlipidemia causes diseases that are seriously harmful to human health, especially cardiovascular and cerebrovascular diseases such as coronary heart disease and atherosclerosis.
- TC total cholesterol
- TG triglyceride
- Hyperlipidemia causes diseases that are seriously harmful to human health, especially cardiovascular and cerebrovascular diseases such as coronary heart disease and atherosclerosis.
- TC total cholesterol
- TG triglyceride
- statin lipid-lowering drugs at therapeutic doses for a long time may have toxic effects on liver function and renal function of patients, and cause rhabdomyolysis in patients, and patients with poor constitution and middle-aged and elderly people. Causes great damage.
- diallyl disulfide is an effective biologically active ingredient extracted from garlic, which has anti-inflammatory, anti-oxidation and inhibition of platelet aggregation. And a variety of biological effects. Compared with diallyl trisulfide which is also extracted from garlic, it is less toxic and simpler in structure. Whether diallyl disulfide is a lipid-lowering component in garlic oil has not been reported.
- the main object of the present invention is to provide a use of diallyl disulfide in the preparation of a medicament for preventing and/or treating hyperlipidemia.
- Diallyl Disulfide (DADS) is an effective biologically active ingredient extracted from garlic. It has many biological effects such as anti-inflammatory, anti-oxidation and inhibition of platelet aggregation. Compared with diallyl trisulfide which is also extracted from garlic, the toxicity is lower and the structure is simpler.
- the present invention proves by experiments that DADS has a therapeutic effect on hyperlipidemia of experimental animals caused by model feed.
- diallyl disulfide for the manufacture of a medicament for the treatment and/or prevention of hyperlipidemia.
- diallyl disulfide in combination with a pharmaceutically acceptable carrier for the manufacture and/or prevention of a hyperlipidemia drug.
- the pharmaceutically acceptable carrier is in a solid or liquid state.
- the carrier preparation in a solid form comprises a powder, a tablet, a dispersion granule, a capsule, a pill, and a suppository; preferably, the powder and the tablet comprise from about 0.1% to about 99.9% of the active ingredient; the solid adjuvant is selected from the group consisting of magnesium carbonate, Magnesium stearate, talc, sugar or lactose; carrier formulations in liquid form include solutions, suspensions and emulsions.
- a pharmaceutical composition for treating and/or preventing hyperlipidemia comprising diallyl disulfide.
- the pharmaceutical dosage form is any one of a tablet, a capsule, a granule, a pill, an oral solution, a suspension, and an injection.
- diallyl disulfide in the manufacture of a medicament or functional food having hypolipidemic efficacy.
- a pharmaceutical composition having a hypolipidemic effect comprising diallyl disulfide.
- a functional food having a hypolipidemic effect comprising diallyl disulfide.
- diallyl disulfide can reduce serum TC, TG and LDL-C in hyperlipidemia rats, and HDL-C is increased, the difference is statistically significant (p ⁇ 0.05).
- the criteria for the evaluation of the auxiliary blood lipid reduction function DADS has an auxiliary blood lipid lowering function. This suggests that diallyl disulfide has a lipid-lowering effect and is clinically useful for the treatment and prevention of hyperlipidemia.
- DADS (CAS 2179-57-9) was purchased from Shandong West Chemical Co., Ltd., and TC, TG, HDL-C and LDL-C kits were purchased from Ningbo Meikang Biotechnology Co., Ltd., and lard was purchased from the market. Beckman AU480 automatic biochemical analyzer, multi-purpose frozen horizontal centrifuge (Heraeu Biofuge Stratos), pipette (Eppendorf), Milli-Q ultrapure water system.
- the feed was added with 20.0% sucrose, 15% lard, 1.2% cholesterol, 0.2% sodium cholate, appropriate amount of casein, calcium hydrogen phosphate and stone powder to prepare a model feed.
- the model experimental group was then randomly divided into a model control group, a 30 mg/kg.bw DADS+ model feed group, and a 60 mg/kg.bw DADS+ model feed group, with 10 animals in each group.
- the test group was prepared with peanut oil to prepare DADS, and the blank and the model control group were given the same amount of peanut oil once a day for 4 weeks, and the intragastric volume was calculated as 1 ml/kg.bw.
- the rats were anesthetized 24 hours after the last administration, and blood was not taken from the diet.
- the serum was separated by centrifugation at 3000 r/min for 15 min.
- Serum total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C) levels were determined using a Beckman AU480 automated biochemical analyzer.
- DADS had a therapeutic effect on hyperlipidemia in experimental animals caused by model feed.
- DADS has an auxiliary blood lipid lowering function.
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Botany (AREA)
- Medicinal Chemistry (AREA)
- Nutrition Science (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
An application of diallyl disulfide in preparing a drug for preventing and/or treating hyperlipemia, and a drug or functional food having a blood lipid reducing function. Experiments prove that diallyl disulfide can reduce the TC, TG and LDL-C in serum of a rat with hyperlipemia, and increase the HDL-C; all differences are statistically significant (ρ < 0.05).
Description
本发明属于医药领域，具体涉及二烯丙基二硫在制备预防和/或治疗高脂血症药物中的应用。The invention belongs to the field of medicine, and particularly relates to the application of diallyl disulfide in the preparation of a medicament for preventing and/or treating hyperlipidemia.
高脂血症(Hyperlipidemia)是由于脂肪转运或代谢异常所致血浆一种或者多种脂质高于正常范围的全身性疾病。一般为总胆固醇(TC)和/或甘油三酯(TG)。高脂血症引起一些严重危害人体健康的疾病，尤其是心脑血管疾病，如冠心病、动脉粥样硬化等。但是目前医药市场上尚缺乏治疗高血脂症的特效药，主要还是依靠西药治疗，如胆汁酸螯合剂、羟甲戊二酰辅酶A还原酶抑制剂和苯氧乙酸类调脂药等。以上西药往往治疗效果不佳，治疗范围都比较狭窄。此外，西药的副作用是显而易见的，比如患者在长期按治疗剂量服用他汀类降脂药物会对病人的肝功能、肾功能产生毒害作用以及引发患者横纹肌溶解症，对于体质差的患者以及中老年人造成很大伤害。Hyperlipidemia is a systemic disease in which one or more plasmas of plasma are higher than the normal range due to abnormal fat transport or metabolism. Generally it is total cholesterol (TC) and/or triglyceride (TG). Hyperlipidemia causes diseases that are seriously harmful to human health, especially cardiovascular and cerebrovascular diseases such as coronary heart disease and atherosclerosis. However, there is currently no specific drug for the treatment of hyperlipidemia in the pharmaceutical market, mainly relying on Western medicine, such as bile acid sequestrant, hydroxymethylglutaryl coenzyme A reductase inhibitor and phenoxyacetic acid lipid-lowering drug. The above western medicines often have poor therapeutic effects and the treatment range is relatively narrow. In addition, the side effects of western medicine are obvious. For example, patients taking statin lipid-lowering drugs at therapeutic doses for a long time may have toxic effects on liver function and renal function of patients, and cause rhabdomyolysis in patients, and patients with poor constitution and middle-aged and elderly people. Causes great damage.
近年来，越来越多的学者将目光转向了中草药。之前有研究表明大蒜油具有降低实验动物血脂的作用，而二烯丙基二硫(Diallyl Disulfide，DADS)是由大蒜中提取的一种有效生物活性成分，具有抗炎、抗氧化、抑制血小板聚集等多种生物学作用。与同样由大蒜中提取的二烯丙基三硫相比，其毒性更低、结构更为简单。二烯丙基二硫是否是大蒜油中的降脂成分，尚未见报道。In recent years, more and more scholars have turned their eyes to Chinese herbal medicine. Previous studies have shown that garlic oil has the effect of lowering blood lipids in experimental animals, and diallyl disulfide (DADS) is an effective biologically active ingredient extracted from garlic, which has anti-inflammatory, anti-oxidation and inhibition of platelet aggregation. And a variety of biological effects. Compared with diallyl trisulfide which is also extracted from garlic, it is less toxic and simpler in structure. Whether diallyl disulfide is a lipid-lowering component in garlic oil has not been reported.
发明内容Summary of the invention
本发明主要目的是提供二烯丙基二硫在制备预防和/或治疗高脂血症药物中的应用。二烯丙基二硫(Diallyl Disulfide，DADS)是由大蒜中提取的一种有效生物活性成分，具有抗炎、抗氧化、抑制血小板聚集等多种生物学作用。与同样由大蒜中提取的二烯丙基三硫相比，其毒性更低、结构更为简单，本发明通过实验证明，DADS对于模型饲料引起的实验动物的高脂血症具有治疗作用。The main object of the present invention is to provide a use of diallyl disulfide in the preparation of a medicament for preventing and/or treating hyperlipidemia. Diallyl Disulfide (DADS) is an effective biologically active ingredient extracted from garlic. It has many biological effects such as anti-inflammatory, anti-oxidation and inhibition of platelet aggregation. Compared with diallyl trisulfide which is also extracted from garlic, the toxicity is lower and the structure is simpler. The present invention proves by experiments that DADS has a therapeutic effect on hyperlipidemia of experimental animals caused by model feed.
为实现上述目的，本发明通过以下技术方案实现：To achieve the above object, the present invention is achieved by the following technical solutions:
本发明第一个方面，提供二烯丙基二硫在制备治疗和/或预防高脂血症药物的应用。In a first aspect of the invention, there is provided the use of diallyl disulfide for the manufacture of a medicament for the treatment and/or prevention of hyperlipidemia.
本发明第二个方面，提供二烯丙基二硫与医药学上可接受的载体配合制备成治疗和/或预防高脂血症药物中的应用。In a second aspect of the invention, there is provided the use of diallyl disulfide in combination with a pharmaceutically acceptable carrier for the manufacture and/or prevention of a hyperlipidemia drug.
进一步，所述医药学上可接受的载体为固态或液态。Further, the pharmaceutically acceptable carrier is in a solid or liquid state.
进一步，所述固态形式的载体制剂包括粉剂、片剂、分散颗粒、胶囊、药丸及栓剂；优选的，粉剂及片剂包含约0.1％至约99.9％的活性成分；固体辅料选自碳酸镁、硬脂酸镁、滑石粉、糖或者乳糖；液态形式的载体制剂包括溶液、悬浮液及乳液。Further, the carrier preparation in a solid form comprises a powder, a tablet, a dispersion granule, a capsule, a pill, and a suppository; preferably, the powder and the tablet comprise from about 0.1% to about 99.9% of the active ingredient; the solid adjuvant is selected from the group consisting of magnesium carbonate, Magnesium stearate, talc, sugar or lactose; carrier formulations in liquid form include solutions, suspensions and emulsions.
本发明第三个方面，提供一种治疗和/或预防高脂血症药物组合物，所述药物组合物含有二烯丙基二硫。In a third aspect of the invention, there is provided a pharmaceutical composition for treating and/or preventing hyperlipidemia, the pharmaceutical composition comprising diallyl disulfide.
进一步，所述药物的剂型为片剂、胶囊剂、颗粒剂、丸剂、口服液、悬浮剂和注射剂中任一种。Further, the pharmaceutical dosage form is any one of a tablet, a capsule, a granule, a pill, an oral solution, a suspension, and an injection.
本发明第四个方面，提供二烯丙基二硫在制备具有降血脂功效的药品或功能食品中的应用。In a fourth aspect of the invention, there is provided the use of diallyl disulfide in the manufacture of a medicament or functional food having hypolipidemic efficacy.
本发明第五个方面，提供一种具有降血脂功效的药物组合物，所述组合物含有二烯丙基二硫。According to a fifth aspect of the present invention, there is provided a pharmaceutical composition having a hypolipidemic effect, the composition comprising diallyl disulfide.
本发明第六个方面，提供一种具有降血脂功效的功能食品，所述功能食品含有二烯丙基二硫。According to a sixth aspect of the invention, there is provided a functional food having a hypolipidemic effect, the functional food comprising diallyl disulfide.
本发明通过实验证明二烯丙基二硫可使高血脂症大鼠的血清TC、TG和LDL-C降低，且HDL-C升高，差异均有统计学意义(p<0.05)。根据国家食品药品监督管理局《关于印发抗氧化功能评价方法等9个保健食品功能评价方法的通知》(国食药监保化[2012]107号)附件6辅助降血脂功能评价方法的判定标准，DADS具有辅助降血脂功能。由此提示，二烯丙基二硫具有降脂的功效，对于治疗和预防高脂血症具有临床意义。The present invention proves that diallyl disulfide can reduce serum TC, TG and LDL-C in hyperlipidemia rats, and HDL-C is increased, the difference is statistically significant (p<0.05). According to the State Food and Drug Administration's Notice on the Evaluation of 9 Health Food Function Evaluation Methods for the Evaluation of Antioxidant Function (Guide to the National Food and Drug Administration [2012] No. 107), the criteria for the evaluation of the auxiliary blood lipid reduction function , DADS has an auxiliary blood lipid lowering function. This suggests that diallyl disulfide has a lipid-lowering effect and is clinically useful for the treatment and prevention of hyperlipidemia.
应该指出，以下详细说明都是示例性的，旨在对本发明提供进一步的说明。除非另有指明，本文使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解的相同含义。It should be noted that the following detailed description is illustrative and is intended to provide a further description of the invention. All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs, unless otherwise indicated.
需要注意的是，这里所使用的术语仅是为了描述具体实施方式，而非意图限制根据本发明的示例性实施方式。如在这里所使用的，除非上下文另外明确指出， 否则单数形式也意图包括复数形式，此外，还应当理解的是，当在本说明书中使用术语“包含”和/或“包括”时，其指明存在特征、步骤、操作、部件和/或它们的组合。It is to be noted that the terminology used herein is for the purpose of describing particular embodiments and is not intended to limit the exemplary embodiments of the invention. As used herein, the singular " " " " " " There are features, steps, operations, components, and/or combinations thereof.
为了使得本领域技术人员能够更加清楚地了解本发明的技术方案，以下将结合具体的实施例详细说明本发明的技术方案。In order to enable those skilled in the art to more clearly understand the technical solutions of the present invention, the technical solutions of the present invention will be described in detail below with reference to specific embodiments.
实施例Example
1材料与方法1 Materials and methods
1.1材料1.1 Materials
1.1.1主要试剂及仪器1.1.1 Main reagents and instruments
DADS(CAS 2179-57-9)购自山东西亚化学股份有限公司，TC、TG、HDL-C和LDL-C试剂盒购自宁波美康生物科技股份有限公司，猪油由市场购买。贝克曼AU480全自动生化分析仪，多功能冷冻水平离心机(Heraeu Biofuge Stratos)，移液器(Eppendorf)，Milli-Q超纯水***。DADS (CAS 2179-57-9) was purchased from Shandong West Chemical Co., Ltd., and TC, TG, HDL-C and LDL-C kits were purchased from Ningbo Meikang Biotechnology Co., Ltd., and lard was purchased from the market. Beckman AU480 automatic biochemical analyzer, multi-purpose frozen horizontal centrifuge (Heraeu Biofuge Stratos), pipette (Eppendorf), Milli-Q ultrapure water system.
1.1.2模型饲料1.1.2 model feed
维持饲料中添加20.0％蔗糖、15％猪油、1.2％胆固醇、0.2％胆酸钠，适量的酪蛋白、磷酸氢钙、石粉，制成模型饲料。The feed was added with 20.0% sucrose, 15% lard, 1.2% cholesterol, 0.2% sodium cholate, appropriate amount of casein, calcium hydrogen phosphate and stone powder to prepare a model feed.
1.2方法根据国食药监保化[2012]107号文中批准的《辅助降血脂功能评价方法》1.2 Method According to the “Evaluation Method of Auxiliary Blood Lipid Function” approved by the National Food and Drug Administration [2012] No. 107
1.2.1实验动物分组与处理1.2.1 Grouping and processing of experimental animals
Wistar雄性大鼠40只，体重180～220g，购自济南朋悦实验动物繁育有限责任公司，实验动物生产许可证号为SCXK(鲁)20140007，实验动物使用许可证号为SYXK(鲁)20130001。于屏障***下以维持饲料饲喂，观察5天。按体重随机分为空白对照组10只(给予维持饲料)和模型实验组30只(给予模型饲料)。模型实验组给予模型饲料9天后，空白对照组和模型实验组大鼠不禁食，经颈静脉采血，分离血清，测定血清TC，根据TC水平确定模型成功。随后将模型实验组随机分为模型对照组、30mg/kg.bw DADS+模型饲料组、60mg/kg.bw DADS+模型饲料组，每组10只动物。受试物组用花生油配制DADS，空白和模型对照组给予等量花生油，每日一次灌胃，连续4周，灌胃体积均按1ml/kg.bw计。在末次给药24h后麻醉大鼠，不禁食取血，以3000r/min离心15min分离血清。40 Wistar male rats weighing 180-220 g were purchased from Jinan Pengyue Experimental Animal Breeding Co., Ltd., the experimental animal production license number was SCXK (Lu) 20140007, and the experimental animal use license number was SYXK (Lu) 20130001. Feed the feed under the barrier system for 5 days. According to body weight, 10 were randomly divided into control group (administration of feed) and model group (30). After the model experiment group was given the model feed for 9 days, the rats in the blank control group and the model experimental group were not fasted, blood was collected through the jugular vein, serum was separated, serum TC was determined, and the model was determined according to the TC level. The model experimental group was then randomly divided into a model control group, a 30 mg/kg.bw DADS+ model feed group, and a 60 mg/kg.bw DADS+ model feed group, with 10 animals in each group. The test group was prepared with peanut oil to prepare DADS, and the blank and the model control group were given the same amount of peanut oil once a day for 4 weeks, and the intragastric volume was calculated as 1 ml/kg.bw. The rats were anesthetized 24 hours after the last administration, and blood was not taken from the diet. The serum was separated by centrifugation at 3000 r/min for 15 min.
1.2.2血生化检测1.2.2 blood biochemical testing
使用贝克曼AU480全自动生化分析仪测定血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)水平。Serum total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C) levels were determined using a Beckman AU480 automated biochemical analyzer.
1.3统计学处理1.3 statistical processing
实验数据以
表示，使用SPSS 20软件进行方差齐性、One-way ANOVA分析，并进行LSD两两比较，以p<0.05认为具有显著统计学差异。
Experimental data Representation of variance homogeneity, One-way ANOVA analysis, and LSD pairwise comparison using SPSS 20 software, with significant statistical differences at p < 0.05.
2结果2 results
2.1 DADS组动物的体重变化2.1 Changes in body weight of animals in the DADS group
由表1可见，DADS组动物的体重与模型对照组比较，无显著性差异(P>0.05)。It can be seen from Table 1 that there was no significant difference in body weight between the DADS group and the model control group (P>0.05).
表1 大鼠体重变化
Table 1 Rat body weight changes
2.2 DADS对大鼠血脂含量的影响2.2 Effect of DADS on blood lipid content in rats
结果(表2)显示，模型实验组动物血清中TC、TG和LDL-C水平与空白对照组相比显著升高(p<0.05)，说明模型建立成功；与模型组相比DADS给药组能够降低由模型饲料所引起的TC、TG和LDL-C的升高(p<0.05)，且60mg/kg.bwDADS组可升高HDL-C(p<0.05)。The results (Table 2) showed that the serum levels of TC, TG and LDL-C in the experimental group were significantly higher than those in the blank control group (p<0.05), indicating that the model was successfully established; compared with the model group, the DADS administration group The increase in TC, TG and LDL-C caused by the model feed was reduced (p<0.05), and the HDL-C was elevated in the 60 mg/kg.bwDADS group (p<0.05).
表2 各组大鼠血清TC、TG、HDL-C、LDL-C含量比较(
n＝10)
Table 2 Comparison of serum TC, TG, HDL-C and LDL-C levels in each group of rats ( n=10)
与空白对照组比较：
*p<0.05，
**p<0.01；与模型对照组比较：
#p<0.05,
##p<0.01。
Comparison with the blank control group: * p < 0.05, ** p <0.01; compared with the model control group: # p < 0.05, ## p < 0.01.
3.结论3. Conclusion
本实验结果表明，模型对照组与空白对照组的血清总胆固醇、血清甘油三酯和低密度脂蛋白胆固醇均升高，差异有统计学意义，说明模型成立。The results of this experiment showed that serum total cholesterol, serum triglyceride and low-density lipoprotein cholesterol were increased in the model control group and the blank control group, and the difference was statistically significant, indicating that the model was established.
经口给予大鼠不同剂量的二烯丙基二硫，与模型对照组比较，30mg/kg.bw DADS组血清总胆固醇和血清甘油三酯降低，差异均有统计学意义(p<0.05)； 60mg/kg.bw DADS组血清总胆固醇、血清甘油三酯和LDL-C降低，且HDL-C升高，差异均有统计学意义(p<0.05)。Different doses of diallyl disulfide were administered orally to rats. Compared with the model control group, serum total cholesterol and serum triglyceride were decreased in the 30 mg/kg.bw DADS group, and the difference was statistically significant (p<0.05). Serum total cholesterol, serum triglyceride and LDL-C were decreased in the 60 mg/kg.bw DADS group, and HDL-C was increased, the difference was statistically significant (p<0.05).
结果表明：DADS对于模型饲料引起的实验动物的高脂血症具有治疗作用。The results showed that DADS had a therapeutic effect on hyperlipidemia in experimental animals caused by model feed.
根据国家食品药品监督管理局《关于印发抗氧化功能评价方法等9个保健食品功能评价方法的通知》(国食药监保化[2012]107号)附件6辅助降血脂功能评价方法的判定标准，DADS具有辅助降血脂功能。According to the State Food and Drug Administration's Notice on the Evaluation of 9 Health Food Function Evaluation Methods for the Evaluation of Antioxidant Function (Guide to the National Food and Drug Administration [2012] No. 107), the criteria for the evaluation of the auxiliary blood lipid reduction function , DADS has an auxiliary blood lipid lowering function.
Claims (9)
- 二烯丙基二硫在制备治疗和/或预防高脂血症药物的应用。The use of diallyl disulfide in the preparation of a medicament for the treatment and/or prevention of hyperlipidemia.
- 二烯丙基二硫与医药学上可接受的载体配合制备成治疗和/或预防高脂血症药物中的应用。The use of diallyl disulfide in combination with a pharmaceutically acceptable carrier for the manufacture and/or prevention of a hyperlipidemia drug.
- 根据权利要求2所述药物，其特征在于，所述医药学上可接受的载体为固态或液态。The medicament according to claim 2, wherein the pharmaceutically acceptable carrier is in a solid or liquid state.
- 根据权利要求3所述药物，其特征在于，所述固态形式的载体制剂包括粉剂、片剂、分散颗粒、胶囊、药丸及栓剂；优选的，粉剂及片剂包含约0.1％至约99.9％的活性成分；固体辅料选自碳酸镁、硬脂酸镁、滑石粉、糖或者乳糖；液态形式的载体制剂包括溶液、悬浮液及乳液。The medicament according to claim 3, wherein the carrier preparation in a solid form comprises a powder, a tablet, a granule, a capsule, a pill and a suppository; preferably, the powder and the tablet comprise from about 0.1% to about 99.9% The active ingredient; the solid adjuvant is selected from the group consisting of magnesium carbonate, magnesium stearate, talc, sugar or lactose; the carrier preparation in liquid form includes solutions, suspensions and emulsions.
- 一种治疗和/或预防高脂血症药物组合物，其特征在于，所述药物组合物含有二烯丙基二硫。A pharmaceutical composition for treating and/or preventing hyperlipidemia, characterized in that the pharmaceutical composition contains diallyl disulfide.
- 根据权利要求5所述药物组合物，其特征在于，所述药物的剂型为片剂、胶囊剂、颗粒剂、丸剂、口服液、悬浮剂和注射剂中任一种。The pharmaceutical composition according to Claim 5, wherein the pharmaceutical dosage form is any one of a tablet, a capsule, a granule, a pill, an oral solution, a suspension, and an injection.
- 二烯丙基二硫在制备具有降血脂功效的药品或功能食品中的应用。The use of diallyl disulfide in the preparation of pharmaceutical or functional foods having hypolipidemic effects.
- 一种具有降血脂功效的药物组合物，其特征在于，所述组合物含有二烯丙基二硫。A pharmaceutical composition having a hypolipidemic effect, characterized in that the composition contains diallyl disulfide.
- 一种具有降血脂功效的功能食品，其特征在于，所述功能食品含有二烯丙基二硫。A functional food having a hypolipidemic effect, characterized in that the functional food contains diallyl disulfide.
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| CN106138282A (en) * | 2016-08-17 | 2016-11-23 | 洪雅县瓦屋山药业有限公司 | A kind of refined even electuary and preparation method thereof for diabetes patient's regulating lipoid and reducing blood pressure |
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| CN101347235A (en) * | 2008-09-08 | 2009-01-21 | 中国科学院新疆理化技术研究所 | Cicer arietinum lipid-lowering nourishing powder and method of preparing the same |
| CN106138282A (en) * | 2016-08-17 | 2016-11-23 | 洪雅县瓦屋山药业有限公司 | A kind of refined even electuary and preparation method thereof for diabetes patient's regulating lipoid and reducing blood pressure |
| CN108014100A (en) * | 2017-12-27 | 2018-05-11 | 山东大学 | Application of the diallyl disulfide in prevention and/or treatment hyperlipidemia is prepared |
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| Title |
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| DHULEY, J.N. ET AL.: "Hypolipidaemic and Antioxidant Activity of Diallyl Disulfide in Rats", PHARMACY AND PHARMACOLOGY COMMUNICATIONS, vol. 5, no. 12, 31 December 1999 (1999-12-31), pages 689 - 696, XP55623073, ISSN: 1460-8081 * |
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