【作者】 杨来发；

【导师】 樊巧玲；

【作者基本信息】 南京中医药大学 ， 方剂学， 2009， 博士

【摘要】 隨著人們生活水準的逐步提高,許多人嗜食肥甘厚味;另外由於工作等原因,又常缺乏運動,這些因素導致肥胖成爲普遍的社會現象,而肥胖又是導致高脂血症的主要因素之一。高脂血症被公認爲可以導致動脈粥樣硬化與冠心病、高血壓病、腦血管病、糖尿病、脂肪肝等多種疾病,對人體健康有著巨大的危害。所以肥胖症與高脂血症已引起世界各國的高度重視。肥胖症的病機往往與痰濕壅盛、氣滯血瘀等及肝脾腎功能失調有關,由於肝失疏泄,氣機不暢,可生痰濕,可致血瘀;木鬱可犯脾土,另一方面,肝腎同源,肝血不足,可致腎虛,故肝功能失調是肥胖症的主要病機,治療當以疏肝或補肝爲主,即以調肝爲主。高脂血症病機與肥胖症相似,均以痰濕(或稱痰濁)爲主要病機,原因是痰濁不化可致瘀血內生或加重臟腑失調,這一提法得到現代實驗研究和臨床的驗證。這給我們的啓發是,治療肥胖症和高脂血症當以調肝化濁法爲本,同時結合調理脾腎,行氣活血,燥濕化痰等治法。肥胖症的診斷,目前國際通用的方法是體格指數BMI(Body Mass Index),計算方法是BMI=體重kg/(身高m)~2,考慮至國人的種屬及形體,診斷標準大致爲:24爲正常上限,24～28爲過重,＞28爲肥胖症。高脂血症的診斷常以血液生化檢查爲依據,中國人血清總膽固醇(TC)的合適範圍爲＜5.20mmol/L(200mg/dl),5.23～5.69mmol/L(201～219mg/dl)爲邊緣升高,＞5.72mmol/L(220mg/dl)爲升高。甘油三酯(TG)的合適範圍爲＜1.70mmol/L(150mg/dl),＞1.70mmol/L(150mg/dl)爲升高。同時參考脂蛋白情況,尤其是低密度脂蛋白(LDL-C),其合適範圍是＜3.12 mmol/L(120mg/dl),3.15～3.61mmol/L(121～139mg/dl)爲邊緣升高,＞3.64mmol/L(140mg/dl)爲升高。目前中醫臨床治療肥胖症和高脂血症的方法豐富多樣,多以辨證論治爲主,也有針灸、推拿等療法,中藥製劑因其使用方便在臨床上也有廣泛應用。西醫治療肥胖症有一系列的方法和措施,主要包括:在全面評估的基礎上,先進行飲食療法和運動療法,還有行爲修正療法或精神療法等非藥物療法,如無效則可以選用藥物治療或外科手術治療。治療肥胖症的西藥可以分爲四類:一是抑制食欲的藥物;二是阻礙消化道吸收的藥物;三是阻礙脂肪囤積的藥物;四是促進代謝的藥物。高脂血症也是先採用飲食療法,無效則採用藥物治療。治療高脂血症的西藥主要包括以下六類:一、羥甲基戊二酸單醯輔酶A(HMG-CoA)還原酶抑制藥,又稱他汀類藥:二、氯貝丁酯類和苯氧乙酸類或稱纖維酸類(fibrates),又稱爲貝特類;三、膽酸鼇合樹脂類;四、煙酸及其衍生物;五、魚油製劑w-3脂肪酸;六、其它包括彈性酶、普羅布考、泛硫乙胺(pantethine)等。雖然中西醫在治療肥胖症和高脂血症方面的方法和藥物較多,但其中也存在許多問題,如關於肥胖的標準問題,肥胖症和高脂血症的治療問題以及高脂血症的中醫規範化研究問題等。爲了克服以上問題,本文根據調肝化濁法是治療肥胖症和高脂血症的主要方法,故以此爲出發點,同時結合健脾補腎、活血等治法,設計了一套簡單的減肥降脂產品,共有四個產品系列,分別爲:1五行酵素菜籽粉代餐包:車前子、萊菔子、白芥子、牛蒡子、決明子、綠豆、紅豆、白扁豆、黑豆、黃豆、黑芝麻、粉狀核桃油、药篛粉、螺旋藻、燕麥、五行酵素粉、寒天粉。五行酵素菜籽粉代餐包以黑芝麻爲君藥,重在補益肝腎,同時也可潤腸通便,減少脂肪及其它成分的吸收而達到減肥降血脂作用,爲代餐包中之主要成分。以核桃油助黑芝麻潤腸通便,更可滋補肝腎;药蒻粉、燕麥都爲食品,可補充營養代餐,又有降血脂減肥功效;螺旋藻則爲目前降血脂減肥的常用藥物,以上均爲臣藥。紅豆、綠豆、黃豆、白扁豆、黑豆五種食品,分別爲五色,各入心肝脾肺腎五臟;車前子入腎經、萊菔子入心經、白芥子入肺經、牛蒡子入脾經、決明子入肝經,五種種子也分入五臟,補充營養代餐,且調補五臟,五臟和則氣血運行通暢,痰濁、瘀血及多餘膏脂皆可自去,以上十味均爲佐藥。以五行酵素粉、寒天粉調和諸藥,爲使藥。全方既可補充營養代餐,且可以通便減肥降血脂(本方以潤下爲主,不會出現明顯的瀉下作用)。本方還可補益肝腎,調補五臟以治本;利濕化痰,疏肝行氣以治標,標本兼治,共起減肥降血脂的目的。2疏肝解毒膠囊:穿心蓮、白花蛇舌草、兔兒菜、車前子、澤瀉、生地、當歸、藿香。穿心蓮、白花蛇舌草、兔兒菜清熱解毒,清除體內所蘊之熱毒,共爲臣藥。生地、當歸活血和血,與薑黃相伍,既可增強活血之力,且又活血和血而不傷血;車前子、澤瀉、藿香利水滲濕化濁;以上共爲佐藥。全方配伍以疏肝瀉火,清熱解毒爲主,兼可活血和血,滲濕化濁。3理肝氣膠囊:薑黃、茵陳、丹參、梔子、五味子、麥冬。方中重用薑黃以疏肝理氣,活血化瘀爲君藥;以茵陳助君藥疏肝理氣,丹參助君藥活血化瘀,共爲臣藥;梔子清熱瀉火,清肝鬱所生之熱;五味子味酸收斂,既可防薑黃、茵陳耗傷正氣,又可酸以入肝而補肝;熱易傷陰,行氣之品也易散傷陰液,故加麥冬養陰扶正,祛邪而不傷正,均爲佐藥。全方以理肝氣爲主,兼有活血清熱之效。4減脂膠囊:紅麴、山藥粉、山楂、當歸、川芎、桃仁、炮薑、甘草、刺五加、桑枝葉、紅景天。減脂膠囊中重用紅麴以健脾化濁,又活血行滯,爲君藥。山楂消食積,化瘀滯,山藥粉健脾助運,共助紅麴健脾化濁爲臣藥。當歸、川芎、桃仁、炮薑、甘草組成生化湯,活血化瘀行滯;刺五加、桑枝葉、紅景天補腎強筋,活血通絡,散結消腫,以上共爲佐藥。全方配伍以化濁健脾爲主,兼活血行滯,祛邪而不傷正。本方重在降血脂,兼有減肥之效,適用于以血脂高爲主的患者。配套產品中,五行酵素菜籽粉代餐包以補益肝腎爲主,肥胖患者可以此代替平日的進餐,既可提供各種營養和能量,又起到減肥降血脂的作用。該產品就是想簡化肥胖患者複雜的食品減肥計畫,方便患者飲食,適合肥胖且血脂較高者。體現了補肝爲主的治法。疏肝解毒膠囊以疏肝瀉火,解熱毒爲主,適合肝鬱氣滯,火毒明顯的肥胖患者;理肝氣膠囊以疏肝理氣,活血化瘀爲主,適合肝鬱氣滯伴有血瘀之象的肥胖患者。兩方體現了疏肝爲主的治法。減脂膠囊則以化濁健脾,活血化瘀爲主,降血脂功效較好,適合脾虛有濕濁,伴血瘀且血脂較高的肥胖患者,體現了化濁治法。此三種產品當辨證或參考血脂情況選擇使用。以上配套產品體現了調肝化濁法降脂減肥的設計理念。疏肝解毒膠囊和理肝氣膠囊中的君藥薑黃在基因毒性安全性評估實驗、動物餵食安全性評估實驗及護肝功能評估三個實驗中,均未見明顯的毒副作用,表明服用安全可靠。減脂膠囊中君藥紅麴在調節血脂實驗中表明具有很好的降低倉鼠和大白鼠血脂作用,且有劑量效應。在急性毒性實驗和慢性毒性實驗中,均顯示無明顯的毒性作用。臨床實驗雖有少數患者出現心灼熱、胃痛、眩暈等不適症狀,但症狀輕微,一般不須特別治療即可自愈。故總體來說,服用紅麴既可降低血脂,又安全可靠,無明顯的毒副作用。以上提示配套產品不僅方便有效,而且安全性較高,具有良好的開發前景。更多还原

【Abstract】 As the standard of living gradually improved,many people start eating too much fat.At the same time,there is also the lack of exercise due to work overload.These factors result in the prevalence of obesity,and obesity is one of the main factors for hyperlipemia It is known that hyperlipemia can lead to the development of serious health problems,such as:atherosclerosis, coronary heart disease,hypertensive disease,cardiovascular diseases,diabetes,fatty liver etc. Therefore,obesity and hyperlipemia have aroused great attention around the world.The pathogenesis of obesity is often associated with phlegm-heat congestion,qi stagnation, static blood,and dysfunctions of the liver,spleen and kidneys.Qi is disturbed due to failure of the liver to convey and disperse,in turn leading to the presence of phlegm dampness and static blood.When the liver qi is stagnated,it will invade the spleen.In addition,liver and kidneys are intimately related;insufficiency of liver blood can lead to kidney deficiency;therefore liver dysfunction is the main cause of obesity.The cause of hyperlipemia is similar to that of obesity, in which phlegm dampness(also known as phlegm turbidity) is the main pathogenesis.This is because unresolved phlegm dampness can bring about blood stasis and aggravated disharmony between bowels and visera;such reasoning is further proved by modern experimental and clinical studies in recent years.This suggests that regulating the liver and resolving turbidity are the essential ways of treating hyperlipemia and obesity.In the intervening time,additional supplementary treatments can be used concurrently;such as regulating spleen and kidneys, promoting qi to activate blood,drying dampness to eliminate phlegm,etc.Obesity is often diagnosed according to the international BMI(Body Mass Index),and the formula is:BMI=weight(kg)/height(meter)~2.In consideration of the Chinese race and body structure,the diagnostic standard is roughly:24 is the upper normal limit,24-28 is overweight, and＞28 is obesity.The diagnosis of hyperlipemia is based on blood biochemistry tests:the normal serum total cholesterol range(TC) for the Chinese is＜5.20mmol/L(200mg/dl),5.23～5.69mmol/L(201～219mg/dl) is the high edge,and＞5.72mmol/L(220mg/dl) is high.The normal level of triglyceride(TG) is＜1.70mmol/L(150mg/dl) and＞1.70mmol/L(150mg/dl) is high.For the lipoproteins,especially low density lipoprotein(LDL-C),the normal range is＜3.12 mmol/L(120mg/dl),3.15～3.61mmol/L(121～139mg/dl) is the high edge,and＞3.64mmol/L(140mg/dl)is high.The choice of treatment for obesity and hyperlipemia in TCM are abundant and diverse today,and they are mainly based on syndrome differentiation.Other ways such as acupuncture and tui-na are applied as well,and Chinese formulated products are also widely used in clinical settings because of their conveniency.In western medicine,there are several ways and measures in treating obesity:on the basis of an overall evaluation,diet adjustment and increase in mild sporting activities are initially introduced to the patient;furthermore behavior correction and psychological treatments may also be conducted.If these treatments are ineffective,that is when medication or surgery comes in. Medication for obesity can be divided into four groups:the first group isto depress appetite;the second group is to hamper absorption of the digestive tract;the third group is to hamper fat storage;the forth group isto accelerate fat metabolism.For the treatment of hyperlilpemia,it also begins with diet modification,then medication would be the next in line.Western medicine in the treatment of hyperlipemia are divided into six groups:the first is hydroxy-methyl-glutaryl coenzyme A(HMG-CoA) reductase inhibitor;the second is androtor and phenoxy acetic acid (also called fibrates);the third is cholic acid combined resin;the forth is nicotinic acid and its derivates;the fifth is fish oil w-3 fatty acid;and the sixth are other drugs including elastase, probucol,pantethine etc.Although TCM and western medicine both contain many strategies and drugs in treating obesity and hyperlipemia,there are many imperfections and problems.For example the standard on obesity,issues associated with treating obesity and hyperlipemia,and the normalization of TCM in the section of hyperlipemia.To overcome the above problems,my thesis is to design simple products or recipes to reduce weight and blood-lipids on the basis of liver regulation and turbidity elimination.Other treatments such as spleen and kidney tonifications,and blood activation are used in conjugation. There are four products:1.Five element ferment seed granule meal replacing pack:plantain seed,radish seed,white mustard seed,great burdock achene,cassia seed,mung bean,hosie ormosia seed,white hyacinth bean,black been,soybean,black sesame,walnut oil flour,elephant-foot yam flour,spirulina,oat, five elements ferment,and Japan agar flour.Black sesame isthe principal drug in the Five element ferment seed powder replacing meal pack.It is used for the purpose of liver and kidney tonifications;it can also lubricate the intestines to promote defecation,and decrease fat absorption to achieve weight and blood-lipid reductions,When walnut oil is used in conjunction with black sesame,it can further lubricate the intestine to relieve constipation,and invigorate the liver and kidneys.Elephant-foot yam flour and oat are both nutritional foods;they can supply nutrition,and reduce weight and blood-lipids. Spirulina is commonly used to reduce weight and blood-lipids.All of the above,except for black sesame,are ministerial drugs.The ten herbs below are adjunctive drugs.Jumble bead,mung bean,soybean,white hyacinth bean and black bean are of five different colors,and each of them enters into one of the five visceral organs:heart,liver,spleen,lungs and kidneys.Plantain seed enters the kidney meridian,radish seed enters the heart meridian,white mustard seed enters the lung meridian,great burdock achene enters the spleen meridian,and cassia seed enters into the liver meridian;furthermore each of the five seeds also enters into a corresponding visceral organ. All together,they can nourish the body and regulate the five visceral organs.In addition,when the five visceral organs are in harmony,smooth qi-blood circulation can be achieved,and phlegm turbidity,static blood,and surplus fat can all be resolved spontaneously.The five element ferment and Japan agar flour are responsible for the coordination of this prescription; and therefore are the messenger drugs.This prescription can replace meals to provide nutrition; in addition it can reduce weight and blood-lipids(through lubrication of the intestines,not strong purgation) of the patient.This prescription can also invigorate the liver and kidneys,coordinate the five visceral organs,drain dampness and resolve phlegm,and disperse depressed liver qi in order to treat both the superfidal and root causes.All together,reductions in weight and blood-lipids can be achieved.2.Liver soothing and toxin detoxifying capsule:curcuma,bupleuri,artemisiae capillaries, cape jasmine fruit,andrographitis,hedyotic diffusa,rabbit vegetable,plantain seed,oriental waterplantain rhizome,rehmannia dride rhizome,Chinese Angelica,Agastache rugosa.In the liver soothing and toxin detoxifying capsule,curcuma is the principal drug,which promotes qi,activates blood,and can enter into the liver meridian.Not only does it soothe the liver and moves qi,but can also activate blood and resolve stagnation;therefore it is a good herb in treating qi stagnation and static blood.Bupleuri disperses depressed liver qi.Curcuma assists the principle drug in soothing the liver and moving qi because its pungent taste can relieve the exterior and disperse hepatic fire.Cape jasmine fruit and artemisiae capillaries contribute to additive efficacy in clearing and dispersing hepatic fire.Andrographitis,hedyotic diffusa,rabbit vegetable all can deer heat and resolve toxin,and they are ministerial drugs.Rehmannia dride rhizome and Chinese angelica activate and soothe blood,and when they are accompanied by curcuma,their blood activating effect can be enhanced without damaging the blood.Plantain seed,oriental water plantain rhizome and Agastache rugosa are adjunctive drugs,and they can drain dampness and resolve turbidity.This prescription mainly soothes the liver,purges fire, dears heat,resolves toxin,activates blood and drains dampness.3.Liver qi regulating capsule:curcuma,artemisiae capillaries,danshen root,cape jasmine fruit,Chinese magnoliavine fruit and ophiopogonis tuber.Curcuma is heavily used in this prescription to soothe the liver and regulate qi,activate blood and resolve stasis;therefore it is the principal drug.Artemsiae capillary can assist the principal drug to soothe the liver,and danshen root can help the principal drug to activate blood and resolve stasis;therefore they are both ministerial drugs.The following herbs are all adjunctive drugs:cape jasmine fruit can clear heat and hepatic fire due to liver depression; ophiopogonis tuber nourishes yin;Chinese magnoliavine fruit is a sour and astringent herb which prevents curcuma and artemisiae from damaging the right qi,and since it is acidic,it can enter into the liver to reinforce it.This prescription mainly soothes the liver,and dears heat and activates blood simultaneously.4.Blood-lipid redudng capsule:red rice,common yan rhizome,hawthorn,Chinese angelica, szechwan lovage rhizome,peach seed,prepared dried ginger,radix glycyrrhizae,manyprickle acanthopanax root,mulberry leaves and gold theragran.In our products,the five element ferment seed granule meal replacing pack mainly invigorates the liver and kidneys.Patients can take it in place of meals,which would be able to supply them the required nutrition and energy,and at the same time reduce weight and blood-lipids.It is a simple and convenient way for patients to lose weight.It is suited for obesity and lipidemia,and its benefits also indude liver invigoration.Liver soothing and toxin detoxifying capsule mainly soothes the liver and purges fire.It has curative effects for fire toxin and qi stagnation due to liver depression in obese patients,Both prescriptions disperse the liver as the main strategy of treatments.Blood-lipid reducing capsule mainly resolves turbidity,invigorates the spleen,and activates blood to dissipate static blood;therefore it suits patients that have spleen asthenia with turbid dampness.The above serial products embody the method of adjusting the liver and resolving turbidity to reduce weight and blood-lipids.All of the above products are proven to be safe in genotoxicity experiments,animal trials and liver function tests.更多还原