1、康脂素藥業有限責任公司 創業計劃書 第四屆挑戰杯康脂素藥業有限責任公司創業計劃書 二零零八年四月目錄第一章：執行概要一、公司簡介·······································&#

2、183;·········································06二、市場描述·······

3、··················································

4、························06三、公司管理························

5、3;·················································

6、3;······08四、公司戰略規劃··········································

7、································08五、場地及設施················

8、83;·················································

9、83;··········08六、投資與財務······································

10、·······································08第二章：康脂素新藥研究一、產品來源········

11、;··················································

12、;·······················09二、原料來源·························

13、83;·················································

14、83;·····09三、新藥研究···········································&

15、#183;·····································09 臨床前研究···········

16、;··················································

17、;··················10 劑量的選擇······························

18、83;················································27康脂素質量標準

19、起草說明·················································&#

20、183;··········28產品生產工藝······································

21、·····································36產品包裝············

22、··················································

23、···················38品種規劃······························

24、··················································

25、·38第三章：生產質量管理一、生產管理··············································

26、···································39二、生產要求·············

27、3;·················································

28、3;·················40三、廠房建設·······························&#

29、183;·················································41

30、四、成本控制·················································

31、································41五、質量管理················

32、3;·················································

33、3;··············41六、產品研發··································&#

34、183;··············································42七、生產工藝流程·

35、3;·················································

36、3;······················42八、設備管理··························&#

37、183;·················································&#

38、183;····42九、物料管理············································

39、·····································44第四章：公司管理一、公司概況··········&#

40、183;·················································&#

41、183;····················45二、產品核心競爭力···························

42、83;··········································46三、公司遠景······&

43、#183;·················································&

44、#183;························47四、公司組織結構及各部門職能······················

45、83;·····························47五、公司的發展戰略··················

46、3;·················································

47、3;·49第五章：市場營銷分析一、市場概述·············································

48、3;···································52二、市場需求分析·············

49、··················································

50、···········53三、消費對象和消費者購買特點····································&#

51、183;················56四、企業綜合分析·······························

52、3;··········································57第六章：市場營銷一、目標市場·····

53、··················································

54、··························58二、市場定位······················

55、3;·················································

56、3;········58三、營銷組合策略········································

57、··································59四、促銷策略··············

58、3;·················································

59、3;················61第七章 財務規劃與投資分析一、資本結構與規模·····························

60、3;········································65二、資金來源及運用········

61、;··················································

62、;············66三、投資的可行性分析····································

63、;·······························66四、投資凈現值和報酬率················

64、3;···············································67五、項目敏感性分析·

65、;··················································

66、;····················69六、項目經營安全性分析···························

67、3;····································70七、投資回報············&#

68、183;·················································&#

69、183;···················70第八章 財務分析一、主要財務假設···························&#

70、183;··············································71二、銷售預測··

71、··················································

72、·····························71三、成本費用核算···················&#

73、183;·················································&#

74、183;····72四、利潤表············································&

75、#183;········································73五、資產負債表·······

76、3;·················································

77、3;····················74六、現金流量表····························&

78、#183;·················································7

79、5七、財務指標分析················································

80、83;·························76八、風險及其評價·······················

81、;··················································

82、;·77九、風險資本的退出···············································

83、·······················78第九章：保險與法律事務第十章：附錄附錄一: 授權委托······················&#

84、183;·················································&#

85、183;·78附錄二：技術實施許可證··············································&

86、#183;·················79附錄三：創業團隊簡介······························&

87、#183;····································81附錄四：創業團隊指導老師···········

88、;·················································84附錄五

89、: 產品包裝·················································

90、·························85附錄六：金銀花外觀圖·······················

91、············································87附錄七：選擇地優勢····&

92、#183;·················································&

93、#183;················88附錄八: 金銀花標準操作規程（SOP）·····························

94、3;················92附錄九：河南新鄉地圖·······························

95、3;···································95附錄十：廠址·············&#

96、183;·················································&#

97、183;·················97附錄十一：廠區平面圖······························&#

98、183;····································98附錄十二：市場狀況問卷調查表··········

99、3;··········································99第一章：執行概要一、公司簡介康脂素藥業有限責任公司（以下簡稱“康脂素藥業”）是一家正在籌

100、建中的集科研、生產、銷售為一體的制藥企業，公司堅持 “關愛人類健康，幸福千萬家庭”的理念，為大眾做質量好療效佳的藥品。公司利用河南大學藥學院康文藝博士的科研成果，生產和銷售中藥一類新藥康脂素，并逐步建立原料生產基地和全方位的銷售網絡。公司以科技為第一生產力，特別注重新產品的研發，在投資初期就計劃建立起以河南大學天然藥物研究所為依托的研發中心，并注重人才的引進及培養。公司廠址選在鄭州市東開發區，鄰近亞洲最大的中轉站之一鄭州火車站。該區交通便利，環境優美，并且可以享受稅收優惠政策。二、市場描述1、流行病學狀況1.1我國高血脂人群現狀2000年亞洲心血管病合作研究結果我國人群總的血脂異常患病率達18

101、.6%，近幾年隨著生活水平大幅度提高，血脂異常逐年增加，我國血脂異常患者近3億人。1.2我國高血脂人群呈現年齡差異2004年中國 MONICA研究第二次危險因素調查，大多數地區女性的總TC水平明顯高于男性，TG水平也存在明顯的差異。1.3我國高血脂人群的分布特點血脂代謝異常在我國不同人群中具有不同的類型特征。我國人群中具有至少一項血脂異常的人群總數逾億人。1.4老年人高血脂特點2004年中國 MONICA研究，血脂異常總患病率高達65.9%。1.5高血脂逐漸低齡化的趨勢2004年4-10月中國 MONICA研究組織流行病學調查組,得出結論:兒童高脂血癥現患率明顯增高,具有地區、年齡、性別的流行

102、病學特征。1.6高血脂和其它心血管疾病的相關性2004年中國 MONICA研究得出高脂血癥為動脈粥樣硬化、冠心病等其他心血管疾病的危險因素。1.7調節高血脂藥物1.7.1西藥類：他汀類藥物包括洛伐他汀、辛伐他汀等；膽汁酸螯合劑代表有考來烯、考來替泊等；貝特類有吉非羅齊；煙酸類；抗氧化劑普羅布考；多烯脂肪酸類有 n- 3 多烯脂肪酸。1.7.2中藥類：降血清膽固醉藥物何首烏、決明、虎杖等和維生素E、黃精、黃酮類、甾體類和枯類化合物；對低密度脂蛋白代謝的影響有決明子山植及山植黃酮；對甘油三醋代謝的影響有黃連、黃琴、絞股藍、大黃、何首烏、大蒜、姜黃、銀杏葉等。；對高密度脂蛋白代謝的影響：山楂、大黃等

103、。2產品競爭力：分別從產品療效競爭力、對比同類產品競爭力和產品市場競爭力三個方面闡述產品競爭力。3產品定位產品適用于各種原因引起的高血脂血癥、血清膽固醇增高癥，也可用于冠心病或慢性肝炎患者的高血脂癥，動脈粥樣硬化的預防和輔助治療。公司建立以后，將針對降脂藥市場的銷售現狀，突出產品優勢，建立售前指導，堅持售后服務。廣泛宣傳健康知識，提高人們的健康意識和對本產品的認知度、認同度，指導高血脂人群合理的、科學的使用本產品。公司初期將在鄭州、開封、洛陽設立分銷中心，采用衛星媒體、地面促銷和及時反饋相結合的方式啟動市場，跨入大型超市、醫院藥房、藥店直銷直營，以產品功效吸引消費者，帶動品牌成長，再以品牌成長

104、帶動企業發展，鞏固繼而擴大市場占有率，并積極拓展廣闊的國際市場。三、公司管理公司性質屬于有限責任制。公司實行事業部型組織機構，面對不同的環境，按照產品或類別、市場用戶、地域以及不同的業務單位分別成立若干事業部，并由這些事業部進行獨立業務經營和分權管理。由股東代表組成董事會，任命一名總經理和兩名副總經理，分別負責下設的財務部、營銷部、公關部（下設危機管理中心和品牌推廣部）、生產部、質量管理部、研發中心和物流部八個部門。四、公司戰略規劃以康脂素產品為核心產品，利用技術優勢，積極開發新產品，并積極申請新藥專利，保護技術成果。管理創新，產品創新，營銷策略創新，充分發揮專項技術優勢，堅持人力資源戰略、企

105、業文化戰略及可持續發展戰略。五、場地及設施 廠址：址選在鄭州市東開發區,位于距鄭州東貨站3公里的東三環路與航海路交叉處，鄰近亞洲最大的中轉站之一鄭州火車站。 設備包括：膠囊切割機,藥用膠囊套合機-JNG400型，NIP系列全自動膠囊充填機，脈沖氣流干燥機，溶膠罐等。六、投資與財務本公司設立在鄭州市東開發區，享受“免二減三”的稅收優惠政策。公司成立初期共需資金1300萬元，其中吸引風險資金550萬元，河南大學注入資金500萬元，短期貸款250萬元。資金用于固定資產投資995萬元，流動資金305萬元。股本規模及結構暫定為：注冊資本為1050萬元，外來風險投資入股300萬元（28.57%），河南大學

106、專利技術入股200萬元（19.05%），資金入股300萬元（28.57%），同時又引入23家風險投資共同入股250萬元（23.81%），利于籌資，化解風險，并為以后擴大規模做準備在公司的經營過程中將獲得充分的市場信息，利用財務杠桿等財務分析工具，為公司在資金管理方面贏得優勢。第二章：康脂素新藥研究一、產品來源該產品是由河南大學天然藥物研究所研發，經河南大學天然藥物研究所技術轉讓，由我公司全權負責該產品的生產與經營。并附術轉讓證書（見附錄二）。二、原料來源金銀花為忍冬科植物忍冬Lonicera japonica Thunb.、紅腺忍冬Lonicera hypoglauca Miq.、山銀花Lon

107、icera confusa DC.或毛花柱忍冬Lonicera dasystyla Rehd.的干燥花蕾或帶初開的花，為中國藥典（2005年版）收載品種，可用于癰腫疔瘡，喉痹，丹毒，熱毒血痢，風熱感冒，溫病發熱，具有清熱解毒，涼散風熱之功效。本公司以河南省封丘縣金銀花種植基地為原料供應地，其金銀花年產量居全國第一位，2003年該縣獲得全國惟一一家金銀花“原產地”認證，2005年順利通過GAP認證。三、新藥研究1臨床前研究1.1 系統提取分離1.1.1 金銀花的粗提取:將金銀花粉碎，用丙酮：水 1：2浸漬提取兩次，第一次7天，第二次3天，得到浸漬提取液，回收溶劑丙酮，得到丙酮部分浸膏，兩次得到的

108、浸膏合并，濾渣在分別用相同的方法分別用甲醇和氯仿提取，最后得到丙酮、甲醇和氯仿三個部分。1.1.2 金銀花的精分離：將所得到的丙酮部分的浸膏用溶劑稀釋，用硅膠、葡聚糖凝膠上柱分離，然后用合適的溶劑極性系統進行洗脫，經過復雜、反復的上柱分離得到單體化合物兩個：分別記做化合物A、B。利用上述方式分別對甲醇部分和氯仿部分進行系統分離，甲醇部分得到一個單體化合物：記做化合物C。氯仿部分進行系統的分離得到三個單體化合物：分別記做化合物D、E、F。經過系統分離總共從金銀花中得到六個單體化合物。1.1.3 六種化合物的結構的測定化合物 A:黃色針狀結晶(丙酮) ,熔點200201。易溶于丙酮、甲醇、乙酸乙酯

109、。溴酚藍和三氯化鐵-鐵氰化鉀反應均為陽性,推測其為酚酸性物質。UVmax(MeOH,nm): 207，258，294；IR(KBr,cm ) : 3410，2925，2856，1655，1603, 1527，1455，1382，1289，1 247，939，879，823，765，638，555；1H-NMR(400 MHz，Acetone ) :7.51(1H ,d ,J =2.0 Hz ,H-22)，7.46(1H, dd, J = 8.2Hz，2.0 Hz，H-26)，6.88(1H, d, J =8.2 Hz, H-25)；13C-NMR(100 MHz，Acetone)：122. 8

110、(C-21)，117. 2(C-22)，145. 4(C-23)，150. 6(C-24)，115. 5(C-5)，123.4(C-26)，167.6(COOH)。化合物B:黃色結晶(丙酮) ,熔點172174。易溶于丙酮、甲醇.溴酚藍和三氯化鐵 -鐵氰化鉀反應均為陽性,推測其為酚酸性物質。IR(KBr ,cm ) :3484 ,3310 ,2965 ,2840 ,1 679,1604,1532,1443,1367,1306,1279,1246,1188,1109,1045,974,933 ,856；H2NMR(400 MHz ,Acetone2D6 +D2 O):7.02(1H ,2d ,J

111、 =2.0 Hz ,H22) ,6.88(1H ,dd ,J= 8.3Hz ,1.9 Hz ,H26) ,6.78(1H ,d ,J = 8.0 Hz,H25) ,7.47(1H2 13d,J=16.0 Hz ,H27),6. 16(1H,d ,J =16.0Hz ,H28) ,3. 66(3H,s,- OCH3 ) ；C2NMR(Acetone2D6 +2D2 O):127.9(C21),111.8(C22),149.3(C23),150.3(C24),116.5(C25),123.8(C26),146.5(C27116.1(C28),170.8( - COOH)。故鑒定該化合物為結構為B。

112、化合物C:白色粉末(甲醇),熔點199201。易溶于甲醇、水。溴酚藍反應為陽性,推測其為有機酸類化合物。IR( KBr ,cm ) :3415,3113,2936 ,1717,1670,1451,1417,1 235,1157,999,854,763,543,1496；H2NMR(400 MHz,D2O):5.67(1H,d,J=7.6Hz,H22),7.40(1H,d,J=7.6Hz,H23) ,3.53(2H ,13q,J=6.8Hz,7.2Hz , -O-CH2 - ),1.05(3H ,t ,J =6.8 Hz ,- CH3)；C2NMR(400 MHz ,D2 O) :167.4(

113、- COOH) ,143.3(C22) ,100.9(C23) ,57.3(-O-CH2- ) ,16.7( - CH3 )。故鑒定該化合物結構為C。化合物D:白色固體(氯仿),熔點7072。易溶于氯仿,H2NMR(400 MHz,CDCl3 ) :139(3H ,t ,J=6.8Hz) ,1. 25(66H) ,3. 65(2H ,t ,J = 6.8Hz)；C2NMR(400 MHz,CDCl3):63.1,-18,31.9,29.7,29.6,25.7,22.7,14.1IR( KBr,cm ):3 395,2919,2850,1738,1613,1467,5,1372,1275,106

114、0,723。故鑒定該化合物結構為D。化合物E:白色固體(氯仿),熔點5456。易溶于氯仿、乙酸乙酯。H2NMR(400 MHz,CDCl3):9(3H ,t ,J =6.8Hz),1.25(42H),1.54(4H) ,3.77(2H ,t ,J = 6.8 Hz)。故鑒定該化合物結構為E。化合物 F:黃色固體(氯仿) ,熔點4042。易溶于氯仿、乙酸乙酯H2NMR(400 MHz ,CDCl3 ) :1(1H ,s ,- CHO) ,7.22(1H ,d ,J =2.8Hz),6.52(1H ,d ,J =3.2 Hz) ,4.7(2H,s,H22),1.25(3H,CH3)。故鑒定該化合物

115、結構為F。1.2 體外實驗研究1.2.1試驗方法及原理（1）DPPH方法及原理DPPH法是20世紀50年代提出來的，最初用于發現食品中的供氫體，后來廣泛用于定量測定酚類物質、黃酮類物質、香辛料類、食品、水果和揮發油等的抗氧化能力。DPPH(二苯代苦味酰基自由基)是一種很穩定的以氮為中心的自由基（見圖1），其孤對電子在515nm附近有強吸收（其乙醇水溶液顯深紫色）。當有供氫能力的抗氧化劑存在時，孤對電子被配對，吸收消失或減弱，而吸光度變小的程度與自由基被清除的程度呈定量關系，因而可用分光光度法進行定量分析。 圖1 DPPH結構及其還原產物Fig.1 Structure of DPPH and i

116、ts reduction by the antioxidant RH（2）ABTS方法及原理 ABTS是一種水溶性的自由基引發劑，該方法就是以此為顯色劑，經活性氧氧化后生成穩定的藍綠色陽離子自由基ABTS+，向其中加入被測物質，當待測物質中含有抗氧化物時，該物質會與ABTS+發生發應而使反應體系顏色褪去，結構式如圖2所示。在ABTS+的最大吸收波長（一般選擇734 nm）處檢測吸光度的變化。檢測結果與以Trolox（6-Hydroxy-2,5,7,8-tetram ethylchroman-2-carboxylic acid ，即 6-羥基-2,5,7,8-四甲基苯并二氫吡喃-2羧酸），一種合

117、成的類似于VE的水溶性物質的對照標準體系比較，換算出被測物質總的抗氧化能力，結果多表示為達到一定濃度測試物質相當的抗氧化能力所需要的Trolox的濃度。 圖2 ABTS及其自由基結構Fig.2 Structure of ABTS and its free radical（3）FRAP方法及原理FRAP方法的原理：在低pH值的溶液中，Fe3+-三吡啶三啞嗪（tripyridyl-triazine，TPTZ）可被抗氧化劑還原為二價鐵形式，呈現出明顯的藍色，并在593 nm處有最大吸收，根據吸光度的大小計算出抗氧化活性的強弱。結果以Fe2+當量或相對于標準抗氧化劑的能力來表示。1.2.2操作方法（1

118、）DPPH方法將樣品用甲醇配制成一系列濃度，取0.1 ml樣品加入3.5 ml DPPH甲醇溶液（0.06 mmol/L），混勻，30 min后測定515 nm處吸光度；同法0.1 ml甲醇+ 3.5 ml DPPH溶液混勻測定吸光度。每份樣品平行操作3次，取平均值。按照以下公式計算自由基清除率： DPPH radical scavenging rate(%) = （Acontrol-Asample）/Acontrol×100式中，Acontrol為DPPH本身在測定波長的吸收，Asample為樣品對DPPH作用后的吸收度數值（除去樣品自身吸收）。（2）ABTS方法將樣品用甲醇配制成

119、一系列濃度，取0.15 ml樣品加入2.85 ml ABTS自由基工作液，混勻，10 min后測定734 nm處吸光度；同法0.15 ml甲醇 + 2.85 ml ABTS自由基工作液混勻測定吸光度。每份樣品平行操作3次，取平均值。按照以下公式計算自由基清除率： ABTS radical scavenging rate(%) = （Acontrol-Asample）/Acontrol×100式中，Acontrol為ABTS本身在測定波長的吸收，Asample為樣品對ABTS作用后的吸收度數值（除去樣品自身吸收）。 （3）FRAP方法將樣品用甲醇配制成一系列濃度，取0.2 ml樣品加入

120、3.8 ml新鮮配制的TPTZ工作液，混勻，37反應30 min后測定593 nm處吸光度。每份樣品平行操作3次，取平均值。若所測定樣品吸光度值超過線性范圍，則需要進一步稀釋樣品。1.2.3試驗結果1.2.3.1 DPPH實驗結果見表1和表2 由表2可知，化合物DPPH法抗氧化活性由大到小依次是C > D > E > F > A > B >LGL表1 陽性對照品清除DPPH自由基的半數抑制濃度樣本數(N)終濃度（µg/ml）A 值(X±SD)抑制率（%）IC50（µg/ml）PG3-0.578±0.002-0.8632

121、.780.028±0.00295.2131.670.087±0.00384.8830.830.295±0.01448.9330.420.425±0.00726.4330.210.505±0.00712.52BHA3-0.575±0.001-3.43316.670.034±0.00194.0938.330.080±0.00386.1534.170.233±0.00659.5932.080.397±0.00630.8431.040.472±0.00317.83BHT3-0.584±

122、;0.001-18.793111.110.045±0.00292.29383.330.065±0.00288.81333.330.204±0.00465.15316.670.343±0.01741.1238.330.428±0.00726.52注：“N”為樣本數表2 化合物清除DPPH自由基的半數抑制濃度No.樣本數(N)終濃度（µg/ml）A 值(X±SD)抑制率（%）IC50（µg/ml）A3-0.593±0.002-32.863111.110.034±0.00194.32383.330.0

123、39±0.00093.42355.560.129±0.00178.28313.890.456±0.00522.8936.940.521±0.00311.89B3-0.586±0.002-42.2135.550.022±0.00296.2532.780.070±0.00288.0531.390.257±0.00056.1430.690.411±0.00929.8630.350.493±0.00215.87C3-0.586±0.002-1.1335.550.022±0.00296

124、.2532.780.070±0.00288.0531.390.257±0.00056.1430.690.411±0.00929.8630.350.493±0.00215.87D3-0.544±0.003-14.33355.560.161±0.01670.4316.670.235±0.00556.838.330.371±0.00331.834.170.384±0.00631.062.080.521±0.0036.46E30.616±0.003-20.06355.560.040±

125、0.00293.45327.780.219±0.00564.50313.890.405±0.00234.3136.940.502±0.00417.1633.470.553±0.0098.75F30.594±0.00224.61383.330.032±0.00194.56355.560.062±0.00389.62327.780.271±0.00154.40313.890.403±0.00432.3836.940.495±0.00617.00LGL3-0.593±0.002-59.431

126、11.110.034±0.00194.32383.330.039±0.00080.42355.560.129±0.00148.28313.890.456±0.00522.8936.940.521±0.00311.891.2.3.2 ABTS實驗結果由表2可知，化合物ABTS法抗氧化活性由大到小依次是C > E > B > F > D > A > LGL圖3 Trolox清除ABTS自由基標準曲線表4 陽性對照品清除ABTS自由基的半數抑制濃度（N=3）No.終濃度（µg/ml）A 值(X±

127、SD)抑制率（%）IC50（µg/ml）RACT50µmol/gPG-0.764±0.007-0.6615509.091.50.036±0.00195.291.250.169±0.00577.880.6250.434±0.00643.190.31250.580±0.00424.080.156250.655±0.00414.27BHA-0.758±0.006-1.725951.1650.001±0.00199.873.750.015±0.00498.022.50.271±0.0

128、0662.251.250.452±0.00440.370.6250.599±0.00720.98BHT-0.758±0.008-6.041696.11250.094±0.00287.612.50.229±0.00469.796.250.375±0.00250.533.1250.512±0.00732.451.56250.605±0.01520.18表5 化合物清除ABTS自由基的半數抑制濃度（N=3）No.終濃度（µg/ml）A 值(X±SD)抑制率（%）IC50（µg/ml）RACT5µmol/gA-0.783±0.006-4.822125.8612.50.067±0.00391.449.3750.118±0.00184.936.250.274±0.00565.013.1250.480