Transcript 第十二章 维生素

Chapter 15
Vitamines
A vitamin is an organic compound
required as a nutrient in tiny amounts by
an organism. A compound is called a
vitamin when it cannot be synthesized in
sufficient quantities by an organism, and
must be obtained from the diet.
The reasons for vitamin deficiency:
(1) Shortage of resource
(2) Reduced absorption
(3) Increase requirements
Vitamins are classified by their biological and
chemical activity, not their structure. Vitamins
have diverse biochemical functions, including
function as hormones, antioxidants, and
mediators of cell signaling and regulators of cell
and tissue growth and differentiation. The largest
number of vitamins function as precursors for
enzyme cofactor bio-molecules (coenzymes), that
help act as catalysts and substrates in
metabolism.
• Classification of Vitamin, by successively
finding time:
• Vitamin A
• Vitamin B
• Vitamin C
• Vitamin D
• Vitamin E
• Vitamin K
• Divided by the solubility:
• Water-soluble vitamins
• Fat-soluble vitamins
15.1 Fat-soluble vitamins
Vitamine A
1. Source
(1)animals: liver, milk, meat and egg
yolk, especially rich in the cod liver oil.
(2)plants: carrot, contain only vitamin A
original, such as β-carotene.
2. The types of Vitamin: A 1 (a) Vitamin
A2 (b)
CH3
H3C CH3
H3C CH3
CH3
CH3
CH2OH
CH2OH
4
CH3
(a)
3
CH3
CH3
( b)
Transferation and clinical application
• Transferation:Vitamin A → retinol →
Retinaldehyde → Rhodopsin → has relationship
with dark vision.
• Clinical purposes: for the treatment and
prevention of vitamin A deficiency disease, such
as corneal softening disease, dry eye, night
blindness and so on.
H3C
CH3
CH3
CH3
CH3
CH2OCOCH3
Properties of vitamione A
Yellow oil or mixture of crystalline and oil.
unstable and easily be oxidized into noactive epoxy compound and further
change into aldehyde and acid.
Applications: agents often be made into oil
solution whereas for storage it should be
put in aluminum or other suitable
container filled with nitrogen, sealed and
preserved in cold and dark place.
Identification: add chloroform solution of
antimony trichloride in chloroform
solution of sample give significant blue,
then change into purple gradually.
Vitamine D
Source of vitamine D
(1) Animals: cod liver oil, liver, egg yolk and milk.
(2) Plants and yeast: containing ergot alcohol,
transfer to vitamin D2 by ultraviolet radiation.
(3) Human skin: containing 7 - dehydro cholesterol,
transfer to vitamin D3 by ultraviolet radiation.
All the Vitamin D are derivatives of sterol, there are
at least 10 vitamine D were discovered
currently,the most important of which is vitamin
D2 and vitamin D3.
Function and clinical usage:
• Vitamine D是一类抗佝偻病维生素的总
称。Vitamine D2 and D3经过在肝脏和
肾脏内两次羟化，代谢成生物活性较强的
1α，25-二羟基维生素D2和D3，具有促进
肠内钙磷的吸收，帮助骨骼钙化的作用。
• Can promote the absorption of
calcium and phosphorus so that help
bone calcification. Clinical used for
the treatment and prevention of
rickets.
Vitamine D2
CH3
H2C
HO
H
CH3
CH3
CH CH CH CH CH(CH3)2
Properties and usage:
① colorless needle crystal or white
crystalline powder
② unstable and easily be oxidized(due to
mutiple double bonds in the molecular)
Storage: filled with nitrogen, sealed and
preserved in cold and shade place.
③ identify: antimony trichloride reaction (a
common steroid compounds reaction):
mixture of the chloroform solution of
antimony trichloride and sample, produce
a significant blue, then purple gradually.
Vitamine E
Vitamin E is the collective name for a set
of 8 related α-, β-, γ-, and δ-tocopherols
and the corresponding four tocotrienols,
which are fat-soluble vitamins with
antioxidant properties.
Source of vitamine E: Particularly high
levels of vitamin E can be found in the
following foods, Avocado,nuts such as
almonds or hazelnuts, red palm oil, seeds,
spinach and other green leafy vegetables,
vegetable oils such as canola, corn,
sunflower, soybean, cottonseed, olive oil
and rice, wheat germ, wholegrain foods,
milk and asparagus.
Function and clinical application of vitamine
E:
Function: anti-infertility and anti-aging。
Clinical application：
Commonly used for the treatment of
infertility, habitual abortion; also can be used
for cardiovascular diseases. Because of the
strong reduction, vitamine often be used as
antioxidant agents in the oil solution.
CH3
Vitamine E
CH3COO
CH3
O
CH3
CH3
Vitamine K
source:
Plants: spinach, Chinese cabbage, radish,
cabbage.
Animals: meat, liver, eggs.
Vitamin K is found chiefly in leafy green
vegetables such as spinach, swiss chard,
and Brassica (e.g. cabbage, kale,
cauliflower, broccoli, and brussels sprouts);
some fruits such as avocado and kiwifruit
are also high in Vitamin K. By way of
reference, two tablespoons of parsley
contain 153% of the recommended daily
amount of vitamin K.
Chemical structure:
All members of the vitamin K group of vitamins share a methylated
naphthoquinone ring structure, and vary in the aliphatic side chain
attached at the 3-position. Phylloquinone (also known as vitamin K1)
invariably contains in its side chain four isoprenoid residues, one of
which is unsaturated.
Menaquinones (also known as vitamin K2) have side chains
composed of a variable number of unsaturated isoprenoid.
维生素K1～K7七种,其中K1～K4均属于2-甲基-1，4-萘醌类，
K5～K7均属于萘胺类。
Vitamine K3
O
CH3
SO3Na
O
3 H2O
• ① White crystal or crystalline powder
• ② unstable and easily decompose
O
CH3
O
SO3Na
O
CH3
+
NaHSO3
O
水溶液与甲萘醌、亚硫酸氢钠间存在动态平衡。遇酸、碱
或空气中氧时，亚硫酸氢钠分解，平衡破坏，产生甲萘醌
沉淀。光和热加速上述变化。
• Identification:水溶液遇氢氧化钠溶液析
出黄色甲萘醌沉淀；遇稀盐酸析出甲萘醌
沉淀，并放出二氧化硫气体。
• Preparation : 注射液常pH调至2～5，加
入焦亚硫酸钠，并且通入惰性气体。
• Storage: sealed and preserved in the
dry and shading place.
15.2 water-soluable vitamines
Water-soluble vitamins include
vitamin B and vitamin C.
Vitamine B1
H3C
N
N
NH2
CH2
S
N
+
CH2CH2OH
CH3
-
Cl
HCl
Physicochemical properties of vitamine B1:
• White crystal or crystalline powder.
• Aqueous solution is acidic.
• Instable, under alkaline condition, the
thiazole ring easily be oxidized to thiol to
lose tha activity.
• Has the properties of tertiary amine
NH2
CH2
N
H3C
CH3
N
N
Cl- HCl + 3 NaOH
CH2CH2OH
S
NH2
CH2
N
H3C
N
N
C
CH C
O
SNa
CH3
CH2CH2OH
+
2 NaCl + 2 H2O
CH2
N
CH3
N
+
CH3
N
NH2
S
CH2CH2OH
CH3
N
N
NaOH
O
CH3
N
N
Cl-
S
CH2CH2OH
• Injection：注射剂不能与碱性药物如磺胺类钠盐、氨茶
碱、碳酸氢钠注射液配伍使用。
• Storage： sealed, preserved in shading place.
• Identification:溶于氢氧化钠溶液中，生成硫醇化合物，继
续被铁氰化钾氧化成硫色素，产物溶于正丁醇中，显蓝色荧
光，加酸呈酸性，荧光即消失，再加碱，荧光又复显。该反
应称为硫色素反应。
Application of vitamine B1:
• For the treatment and prevention of
disease caused by the deficiency of
vitamin B1, such as beriberi. For the
treatment of neuritis and also for the
adjuvant treatment of many diseases.
Vitamine B2
CH2OH
(CHOH)3
CH2
H3C
N
H3 C
N
N
O
NH
O
Properties and application of vitamine B2:
• Orange yellow crystalline powder, its aqueous solution
presentes yellow-green fluorescence, the strongest
fluorescence in the pH of 6.0 ~ 7.0. However, by adding
acid or alkali, fluorescence disappeared immediately.
• With the properties of acid and alkaline:酰亚胺结构显酸性，易
溶于氢氧化钠稀溶液；N5位的叔胺结构显碱性，溶于稀酸中。
• Unstable and is prone to produce photochemical reaction
• Storge：preserved in shading place and sealed。
• With oxidization and reduction
• Identification:能被强氧化剂如铬酸和高锰酸钾所氧化而破坏；如遇
还原剂如连二亚硫酸钠或维生素C等，又可被还原为无荧光的二氢核
黄素并从水中析出，二氢核黄素悬浊液在空气中振荡能再被氧化成核
黄素。
• Clinical usage: for the treatment and prevention of cheilitis,
glossitis, seborrheic dermatitis and conjunctivitis.
防治唇炎、舌炎、结膜炎和脂溢性皮炎。
CH3
HO OH OH
CH2 CHCHCHCH2OH
H3C
N
H3C
N
N
O
NH
光
O
H+或OH-
N
H3C
N
N
O
NH
O
N
H3C
N
光
(18-12)
H+ 或中性
H3C
N
H3C
N
N
O
NH
O
H
N
O
NH
O
CH2COOH
H3C
OH-
H3C
Vitamine C
CH2OH
H
C
OH
O
H
OH
O
OH
Properties of vitamine C:
1．Acid (hydroxy on C3）
2．unstable①easily be oxidized
OH
O
HO
O
CHCH2OH O
H
OH
OH
O
O
O
CHCH2OH
OH-
O
COOH
O
O
O
C
H2O
OH
CHOH
CH
[O]
CH2OH
OH
H
C
OH
HO
C
H
CH2OH
+
COOH
COOH
• ② Decomposition in storage:贮存中颜色加深，主要原
因是在空气、光线、温度等的影响下，氧化生成去氢维生素
C，在一定条件下发生脱水，水解和脱羧反应而生成糠醛，
以至聚合呈色。
OH
O
O
HO
CHCH2OH
O
CHCH2OH
[O]
O
HO
H2O
O
- 2 H2O
OH
O
OH
O
OH
O
O
HOOC C
- H2O ，
- CO2
O
O
CHO
O
为了避免本品的分解，制片剂时，采用干法制粒；配制注射液时，应使用
二氧化碳饱和的注射用水，pH控制在5.0～7.0之间，并加入EDTA和焦亚
硫酸钠等作为稳定剂，通入二氧化碳或氮气等惰性气体置换安瓿液面上的
空气；贮存时应遮光，密封保存。
• Clinical usage:防治坏血病，预防冠心病
及各种急慢性传染病的辅助治疗。另外常
作水溶液制剂的抗氧剂。
• For the treatment and prevention of
scurvy and coronary heart disease.
For the adjuvant therapy of various
acute and chronic infectious
diseases. Additionally used as
antioxidant agents for some aqueous
solution.