Vitamin B1 and its derivatives

29.36 Provitamins and vitamins, natural or reproduced by synthesis (including natural concentrates), derivatives thereof used primarily as vitamins, and intermxtures of the foregoing, whether or not in any solvent (+). - Vitamins and their derivatives, unmixed : 2936.21 - - Vitamins A and their derivatives 2936.22 - - Vitamin B1 and its derivatives 2936.23 - - Vitamin Bzand its derivatives 2936.24 - - D- or DL-Pantothenic acid (Vitamin B3 or Vitamin B5)and its derivatives 2936.25 - - Vitamin B6 and its derivatives 2936.26 - - Vitamin B12 and its derivatives - - Vitamin C and its derivatives 2936.28 - - Vitamin E and its derivatives 2936.29 - - Other vitamins and their derivatives 2936.90 - Other, including natural concentrates 2936.27 Vitamins are active agents, usually of complex chemical corn osition, which are obtained from outside sources and are essential for the proper functioning of uman or other animal organisms. The cannot be synthesised by the human body and must therefore be obtajned in final or nearly f m form (provitarnins) from outside sources. They are effective in relatively minute amounts and may be re arded as exo enous biocatalysts, their absence or deficiency giving rise to metabolic distur ances or " de lciency diseases ". % f B This heading includes : (a) Provitamins and vitamins, whether natural or reproduced by synthesis, and derivatives thereof used primarily as vitamins. (b) Concentrates of natural vitamins (e.g., of vitamin A or of vitamin D); these are enriched forms of these vitamins. These concentrates may be used as such (e.g,, for adding to animal feeding stuffs), or they may be worked up for the isolation of the vitamin. (c) Intermixtures of vitamins, of provitamins or of concentrates, such as, for instance, natural concentrates of vitamins A and D in various proportions, to which an additional quantity of vitamin A or D has been added subsequently. (d) The above products diluted in any solvent (e.g., ethyl oleate, propane-1,2-diol, ethanediol, vegetable oils). The products of this heading may be stabilised for the purposes of preservation or transport : - by adding anti-oxidants, - by adding anti-caking agents(e.g., carbohydrates), - b coatin with appropriate substance (e.g., gelatin, waxes or fats), whether or not pYasticise%7or - by adsorbing on appropriate substances (e.g., silicic acid), provided that the quantity added or the processing in no case exceeds that necessary for their preservation or transport and that the addtion or rocessing does not alter the character of the basic product and render it particulary suita le for specific use rather than for general use. g List of products which are to be classified as provitamins or vitamins within the meaning of heading 29.36. The list of products in each of the following groups is not exhaustive. The products listed are examples only. (A) PROVITAMINS Provitamins D. in (1) Non-irradiated ergosterol or provitamin D,. Ergosterol is found in the e r G f te akes brewer's yeast, in mushrooms and in other fungi. It has no vitamin activity. which become yellow on exposure to air; insoluble in water but soluble in alcohol and benzene. (2) Non-irradiated 7-dehydrocholesterol or provitamin D3.Found in the skin of animals. It is extracted from wool grease or from by-products of the manufacture of lecithin. Platelets insoluble in water but soluble in organic solvents. (3) Non-irradiated 22,23-dihydroergosterol or provitamin D4. (4) Non-irradiated 7-dehydro-J-sitosterol or provitamin D5. (5) Non-irradiated ergosteryl acetate. (6) Non-irradiated 7-dehydrocholesteryl acetate. (7) Non-irradiated 22,23-dihydroergosteryl acetate. (B) VITAMINS A AND DERIVATJYES THEREOF USED PRIMARILY AS VITAMINS Vitamins A (growth or anti-xerophthalmic vitamins are essential for the normal development of the body, particularly of the skin, the bones an the retina. They help to maintain normal infection-resistant epithelial tissue and are required for normal reproduction and lactation. They are 1iposoIuble and, as a rule, insoluble in water. d (1) Vitamin Al alcohol (axerophthol, retinol (INN)). Vitamin Al aldehyde (retinene-1, retinal). Vitamin Al acid (tretinoin (INN), retinoic acid). Vitamin Al is found, as the alcohol or in the form of fatty acid esters, in animal products (salt water fish, dairy roducts, eggs). It is rnainly extracted fi-om fi-esh fish liver oil, but may also be obtained y synthests. It is a yellow solid which may remain oily at room temperature but, when cooled, it forms yellow crystals. Since ~tis unstable in air, it is often stabilised by the addition of anti-oxidants. I! (2) Vitamin A2 alcohol (3-dehydroaxerophthol, 3-dehydroretinol). Vitamin A2 aldehyde (retinene-2,3-dehydroretinal). Vitamin A2 is not found as wide1 in nature as vitamin A,. It is extracted from h s h water fish. The alcohol does not crystallse; the aldehyde, however, occurs as orange crystals. (3) Vitamin A acetate, palmitate and other fatty acid esters. These products are obtained from synthetic vitamn A; they are all sensihve to oxidation. The acetate is a yellow powder and the palmitate is a yellow liquid, which may crystallise in its pure state. (C) VITAMIN B1AND DERIVATIVES TEIERlEOF USED PRIMARILY AS VITAMINS Vitamin B1 is the anti-neuritic vitamin, essential for the in carbohydrate metabolism. It is used in the treatment o for the maintenance of good appetite. This vitamin is heat. beri-beri. It is important gastric disturbances and and is not very stable to (1) Vitamin B1 (thiamine (INN , aneurine). Thiamine is found in most animal and vegetable tissues e.g., in cereal grain usks, brewers' yeast, pork, liver, dairy roducts, eggs, etc.); it is usual y obtained synthetically. It is a white crystalline powder, sta le to air. I h g (2) Thiamine hydrochloride. A white crystalline powder. Hygroscopic, not very stable. (3) Thiamine mononitrate. White crystalline powder, fairly stable. (4) Thiamine-1,5-salt (aneurine-1,5-salt, aneurine naphthaIene-l,5-disulphonate). (5) Thiamine salicylate hydrochloride (aneurine salicylate hydrochloride). (6) Thiamine salicylate hydrobromide (aneurine salicylate hydrobromide). (7) Iodothiamine. (8) Iodothiamine hydrochloride. (9) Iodothiamine hydriodide. (10) Orthophos horic ester of vitamin BI or thiamine orthophosphate and the mono- and dihydroch oride and the monophosphate of this ester. f (11) Nicotinic ester of vitamin Bl. (D) VITAMIN BzAND DERIVATIVES THEREOF USED PRIMARILY AS VITAMINS Vitamin B2 is a nutrition and growth-promoting vitamin; it is biologically important as a utilisation factor for carbohydrates. It is soluble in water and stable to heat. (1) Vitamin B2 (riboflavine (INN), lactoflavine . Riboflavine is found in association with vitamin B1 in many products and foodstu s. It may be extracted fiom distiller's and fermentation residues and fiom beef liver, but generally it is obtained by synthesis. Orange yellow crystals, fairly sensitive to light. d (2) 5'-orthophos horic ester of riboflavine or riboflavine 5'-orthophosphate and its sodium or &ethanolnmine salt. These products are more soluble in water than is riboflavine. (3) (Hydroxymethy1)riboflavine or methylolriboflavine. (E) D- OR DL-PANTOTHENIC ACID (ALSO KNOWN AS VITAMIN B3 OR VITAMIN Bs)AND DERIVATIVES THEREOF USED PRIMARILY AS VITAMINS These compounds lay a part in preventing ey hair, in the development of skin, and in fat and carbohydrate meta olism. They are essent~ for the activity of the glands and liver, and of the gastro-mntestinal and respiratory tracts. They are soluble in water. g (1) D- or DL- Pantothenic acid (N-(a,ydihydroxy-,!?,,!?-dimethylbutyry. This vitamin, also known as vitamin B3 or vitarmn B5,is found in all living cells and tissues (e.g., in the liver and kidneys of mammals, in the pericarp of rice, in brewers' yeast, milk, crude molasses, etc.). It is general1 obtained by synthesis. Yellow viscous oil; slowly soluble in water and most organic so vents. f (2) Sodium D- and DL-pantothenate. (3) Calcium D- and DL-pantothenate. This white powder, soluble in water, is the most common form of vitarmn B3. (4) Pantothenyl alcohol or pantothenol (D- and DL-) (a,y-dihydroxy-N-3-hydroxypropylB$-dimethylbutyramide). Viscous liquid, soluble in water. (5) DTpantothenol ethyl ether @-a,~-dihydroxy-N-3-ethoxypropyl-~~-~methy1~de). Vlscous liquid, water-miscible and readily soluble in organic solvents. (F) VITAMIN B6AND DERIVATIVES THEREOF USED PRIMARILY AS VITAMINS Vitamin B6is the anti-dermatitic vitamin skin protection). It plays a part in the nervous system, nutrition and in amino-acid, protein and at metabolism. It is used to alleviate sickness due to pregnancy or post-operative conditions. It is soluble in water and fiiirly sensitive to light. k (1) Pyridoxine (INN) or adermin (pyridoxol) (3-hydroxy-4,5-bis(hydroxymethy1)-2-methylpyridine). Pyridoxal(4-fomyl-3-hydroxy-5-hydroxpethyl-2-methylpyridine). Pyridoxamine (4-aminomethyl-3-hydroxy-5-hydroxymethyl-2-methylpyridine). These three forms of vitamin B6 are found in brewers' yeast, su ar cane, the outer part of cereal grains, rice bran, wheat germ oil, linseed oil, and in t e liver, meat and fat of mammals and fish. This vitamin is nearly always made synthetically. K (2) Pyridoxine hydrochloride. Pyridoxine orthophosphate. Pyridoxine tripalmitate (tripalmitate ester of pyridoxine). Pyridoxal hydrochloride. Pyridoxamine dihydrochloride. Pyridoxamine phosphate. These are the normal forms of vitamin B6.Colourless crystals or flakes. (3) Pyridoxine orthophosphoric ester and its sodium salt. Pyridoxal orthophosphoric ester and its sodium salt. Pyridoxamine orthophosphoric ester and its sodium salt. (G) VITAMIN B9AND DERIVATnTES THEREOF USED PRIMARILY AS VITAMINS Vitamin B9is essential for the development of blood cells and is effective in treating pernicious anaemia. It is found in spinach and green plants, in brewers' yeast and in the liver of animals, but is usually obtained by synthesis. (1) Vitamin B9(folic acid (INN) or pteroylglutamic acid) and the sodium salt and the calcium salt of this vitamin. (2) Folinic acid (INNM) (5-formyl-5,6,7,8,-tetrahydropteroylglutamicacid). 0VITAMIN B12(CYANOCOBALAMIN (INN)) AND OTHER COBALAMINS (HYDROXOCOBALAMIN(INN), METHYLCOBALAMIN, NITRITOCOBALAMIN, SULPHITOCOBALAMIN, ETC.) AND THEIR DERIVATIVES Vitamin BIZis even more effective than vitamin B9in treating pernicious anaemia. It has a high molecular weight and contains cobalt. It is found in various forms in the liver and flesh of mammals and of fish, in eggs and in milk. It is obtained from spent antibiotic liquors, sugar beet molasses, whey, etc. Dark red crystals, soluble in water. (IJ) VITAMIN C AND DERIVATIVES THEREOF USED PRIMARXLY AS VITAMINS Vitamin C is the anti-scorbutic vitamin, and increases resistance to infections. It is soluble in water. (1) Vitamin C (L- or DL-ascorbic acid INN)). Ascorbic acid is contained in many foodstuffs of vegetable (fruit and green vegeta les, otatoes, etc.) or animal (liver, spleen, adrenal glands, brains, milk, etc.) origin; it can ge extracted from lemon juice, green and red peppers, green aniseed leaves, and from residual liquors from the treatment of agave fibres. Nowadays, it is obtained almost exclusively by synthesis. It is a white crystallme powder, fairly stable in dry air, and acts as a strong reducing agent. (2) Sodium ascorbate. (3) Calcium ascorbate and magnesium ascorbate. (4) Strontium (L) ascorbocinchoninate (strontium (L) ascorbo-2-phenylquinoline-4carboxylate). (5) Sarcosine ascorbate. (6) L-Arginine ascorbate. (7) Ascorbyl palmitate. This liposoluble form of vitamin C is also used as an emulsifier and anti-oxidant for fats and oils. (8) Calcium hypophosphitoascorbate. (9) Sodium ascorboglutamate. (10) Calcium ascorbogIutamate. (K) VITAMINS D AND DERJVATIVES THEREOF USED PRIMARILY AS VITAMINS Vitamins D are the anti-rachitic vitamins. They regulate the utilisation of phosphorus and of calcium in the organism and assist in the development of teeth and bones; they are liposoluble. They are obtained by activation or irradiation of various provitamins D, which are sterols or sterol derivatives normally produced and transformed by the organism. (I) Vitamin D2and derivatives thereof with similar activity. (a) Vitamin D2or activated or irradiated ergosterol cdciferol, ergocalciferol). A white crystalline owder, becoming yellow when expose to air, light or heat; insoluble in water, solu!l le in fats. It is found in cocoa beans and in fish liver; generally obtained by activation or irradiation of provitamin D2. (b) Acetate and other fatty acid esters of vitamin DZ. (2) Vitamin D3 and derivatives thereof with similar activity. (a) Vitamin D3 or activated or irradiated 7-dehydrocholesterol (cholecalciferol). White c stalline owder. It deteriorates slowly when ex osed to air; insoluble in water, so uble in ats. It can be extracted from fish oil and &rn fish liver oil, but is generally obtained by activating or irradiating provitamin D3.It has a stronger activity than vitamin Dz. ? (b) Activated or irradiated 7-dehydrocholesteryl acetate and other fatty acid esters of vitamin DJ. (c) Vitamin D3-cholesterol molecular compound. (3) Vitamin D4 or activated or irradiated 22,23-dihydroergosterol. White flakes; lower biological activity than vitamin D2. (4) Vitamin DSor activated or irradiated 7-dehydro-p-sitosterol. (L)VITAMIN E AND DERNATnTES THEREOF USED PRIMARILY AS VITAMINS Vitamin E is the anti-sterility vitamin, and is important in the nervous and muscular systems. It is liposoluble. a (1) Vitamin E or (D- and DL-) a-toco herol; B- and y-toco herol. Toco herol is found in various vegetable and animal pro ucts (e.g., cocoa anacotton seez, vegetable oils, ous plant leaves, salad leaves, lucerne, dairy products). It is extracted mainly from w lei?-eat germ oil. The racemic isomers are obtained b synthesis. Colourless oil, insoluble in water, soluble in alcohol, benzene and fats; it is stab e to heat in the absence of oxygen and light. Its anti-oxidising properties also make it suitable for use as an inhibiting agent for fats and foodstuffs. T (2) a-Tocopheryl acetate and a-tocopheryl hydrogen succinate; a-tocopheryl poly(oxyethy1ene) succinate (also known as a-tocopheryl polyethylene glycol succinate). (3) Disodium a-tocopheryl phosphate. (4) Tocopheryl diaminoacetate. (M) VITAMIN H AND DERIVATIVES THEREOF USED PRIMARILY AS V I T M N S Vitamin H is necessary for the growth of certain micro-organisms; it is essential for the health of the skin, muscles and nervous system. It is soluble in water and stable to heat. (1) Vitamin H or biotin. Biotin is found in egg-yolk, in kidneys and liver, milk, brewers' yeast, molasses, etc. It is prepared by synthesis. (2) Biotin methyl ester. (N) VITAMINS K AND DERIVATIVES THEREOF USED PRIMARILY AS VITAMINS Vitamins K are anti-haemorrhage factors; they accelerate blood coagulation by maintaining the prothrombin content and increasing capillary resistance. (I) Vitamin K1. (a) Phytomenadione (INN), phylloquinone, phytonadione or 3-phytylmenadione (2-methyl-3- hytyl-l,4-naphthoquinone). Extracted from dry lucerne; also found in hazel and c estnut leaves, barley and oat shoots, cabbage, cauliflower, spinach, tomatoes, vegetable oil, etc. Also obtained by synthesis. Light yellow oil, soluble in fats; stable to heat but unstable to sunlight. R (b) Vitamin K,oxide (epoxide) (2-methyl-3-ph 1-1,4-naphthoquinone-2,3-oxideor 2methyl-3-phytyl-2,3 -epoxy-2,3-dihydro- 1,4-nap thoquinone). T (c) Dihydrophylloquinone(3-dihydrophytyl-2-methyl-l,4-naphthoquinone). (2) Vitamin K2or farno uinone (3-difarnesyl-2-methyl-l,4-naphthouinone). Extracted kom the meal of utrefie sardines. Weaker activity than vitamin I. Yellow crystals very unstable to ligt. d (0)VITAMIN PP AND DERIVATIVES THEREOF USED PRIMARILY AS VITAMINS Vitamin PP is the anti-pellagra vitamin essential for growth, oxidations, cellula respiration, protein and carboxyhydrate metabolism. liver, (pyridine-B-carboxylic acid, niacin). Animal sources (e (1) Nicotinic acid ( kidney, fksh m e a ~ m m m a l and s certain kinds of fish) and vegetable sources giewers' etc . Obtained s thetically. Colourless crystals, soluble yeast, cereal germs and peric BIPy,stab e to heat an oxidation. 1n alcohol, liposoluble; relative -1 d/" (2) Sodium nicotinate. (3) Calcium nicotinate. (nicotinic acid amide, niacinamide). Sources, pro erties and uses as (4) Nicotinamide ( the nicotinic acld. 0 tained synthetically. Soluble in water and stable to eat. ""b (5) Nicotinamide hydrochloride. (6) Nicotinomorpholide. E EXCLUSIONS The heading excludes : (1) The products listed below which, though sometimes called vitamins, have no vitamin activity or have a vitamin activity which is of secondary importance in relation to their other uses : (a) mesoInosito1, myoinositol, i-inositol or mesoinosite (heading 29.06), used for gastro-intestinal and hepatic disturbances (especially as calcium or magnesium hexaphosphates). (b) Vitamin HI:p-aminobenzoic acid heading 29.22), which is growth inducing and neutralises the antibacteriostatic effects of some sufphonamides. (c) Choline or bilineurine (heading 29.23), which stabilises fat metabolism. (d) Vitamin B4 : adenine or 6-aminopurine (heading 2933), used in post-medicinal haematological accidents and in tumor therapeutics. (e) Vitamin C2 or P : citrin, hesperidin, rutoside (rutin), aesculin (heading 29.38), used as antihaernorrhage factors and to develop capillary reststance. (f) Vitamin F : linoleic or linolic acid (a-and /?-),linolenic acid, arachidonic acid (heading 38.23), used to treat dermatitis and liver disturbances. (2) Synthetic substitutes for vitamins : (a) Vitamin K3 : menadione, mena hthone, methylnaphthone or 2-methyl-1,4-na hthoquinone; sodium salt of 2-rnethyl-1,4-na h%oquinone bisulphits derivative (heading 29.l$ Menadiol or 1,4-dihydroxy-2-methyl-naphti'alene (heading 29.07). (b) Vitamin Kg : 1,4-diamino-2-methylnaphthalene(heading 29.21). (c) Vitamin Kg:4-amino-2-methyl-1-naphthol hydrochloride (heading 29.22). (d) Cysteine, a vitamin B substitute (heading 29.30). (e) Phthiocol : 2-hydroxy-3-methyl-l,4-naphthoquinone, a vitamin K substitute (heading 29.41). (3) Sterols, other than ergosterol : cholesterol, sitosterol, stigrnasterol and the sterols obtained during preparation of vitamin D2 (tachysterol, lumisterol, toxisterol, suprasterol) (heading 29.06). (4) Medicaments of heading 30.03 or 30.04. (5) Xanthophyll, carotenoid of natural origin (heading 32.03). and -carotenes and cryptoxanthin) because of their use as colouring (6) Provitamins A (a-, substances (headmg 2.03 or 2.04). 4 J