2937 90 — Hormones, natural or reproduced by synthesis; derivatives and structural analogues thereof, used primarily as hormones (excl. polypeptide hormones, protein hormones, glycoprotein hormones, steroidal hormones, catecholamine hormones, prostaglandins, thromboxanes and leukotrienes, their derivatives and structural analogues, and amino-acid derivatives, and products of 3002 10)

2937 Hormones, prostaglandins, thromboxanes and leukotrienes, natural or reproduced by synthesis; derivatives and structural analogues thereof, including chain modified polypeptides, used primarily as hormones (+): – polypeptide hormones, protein hormones and glycoprotein hormones, their derivatives and structural analogues: 2937 11 – – somatotropin, its derivatives and structural analogues 2937 12 – – insulin and its salts 2937 19 – – other – steroidal hormones, their derivatives and structural analogues: 2937 21 – – cortisone, hydrocortisone, prednisone (dehydrocortisone) and prednisolone (dehydrohydrocortisone) 2937 22 – – halogenated derivatives of corticosteroidal hormones 2937 23 – – oestrogens and progestogens 2937 29 – – other 2937 50 – prostaglandins, thromboxanes and leukotrienes, their derivatives and structural analogues 2937 90 – other This heading covers: (I) Natural hormones, which are active substances formed in living human or animal tissues, capable in very small quantities of inhibiting or stimulating the functions of various organs, either by acting on them directly or by controlling the synthesis or secretion of secondary or tertiary hormonal systems. The principal defining characteristic of a hormone is its ability to bind stereospecifically to a receptor molecule so as to produce a hormonal action. The secretion of these substances, generally by the endocrine glands, is regulated by the sympathetic and parasympathetic systems. Hormones are carried by the blood, the lymph or other body fluids. They may also be produced in endocrine and exocrine glands or in various cellular tissues. Transport of hormones in the blood is not necessary for hormonal

effect. The effect can occur after the release of hormones into the intercellular fluid and their subsequent binding to receptors of nearby cells (paracrine regulation) or to receptors of hormone-releasing cells (autocrine regulation). (II) Natural prostaglandins, thromboxanes and leukotrienes are compounds secreted by the body and resemble locally acting hormones. Prostaglandins are CLA hormones or hormone-like substances synthesized in the tissues in which they act (or act in the local cellular microenvironment), binding to specific cellular receptors, and act as important modulators of cellular activity in many tissues. It is said that these three chemically related families (derivatives of arachidonic acid) have a "hormone-like effect". (III) Natural hormones, prostaglandins, thromboxanes and leukotrienes obtained by synthesis (including biotechnology methods) and having the same chemical structure as natural substances. (IV) Derivatives of natural or synthetically produced hormones, prostaglandins, thromboxanes and leukotrienes, such as salts, halogenated derivatives, cyclic acetali, esters, etc., including complex derivatives (e.g., esters of halogenated derivatives), provided that they are used primarily as hormones. (V) Analogues of hormones, prostaglandins, thromboxanes and leukotrienes. The term “analogue” refers to chemical compounds having a structural similarity to the parent compound, but which cannot be considered derivatives. Compounds having a structural similarity to natural compounds, but in whose structure one or more atoms have been replaced by others. (a) Analogues of polypeptide hormones are obtained by attaching, separating, substituting, or altering certain amino acids in the natural polypeptide chain. Somatrem (INN) - an analogue of growth hormone (somatotropin) is the result of attaching a terminal amino acid to a molecule of natural somatotropin. Ornipressin (INN) – an analogue of natural argipressin (INN) and lypressin (INN) is the result of the substitution of an internal amino acid in the molecule of argipressin or lypressin. Synthetic gonadoliberines, buserelin (INN), nafarelin (INN), fertileline (INN), leiprelin (INN) and lutherelin (INN) analogues of gonadorelin (INN) are the result of altering or replacing certain amino acids in the polypeptide chain of natural gonadorelin. Hyractide (INN) – The analogue of corticotropin (INN) has the same structure as the first 18 amino acids in the natural corticotropin, but the first amino acid replacement puppy. Metroleptin (INN), an analogue of leptin, is a recombinant methionyl derivative of human leptin. Saralasine (INN), which, compared to the angiotensin II molecule, contains three different amino acids, should be considered as a structural anologue of angiotensin II, despite the fact that it is its antagonist (the first lowers blood pressure, and the second increases). Analogues of steroid hormones must have a gonan structure altered by contracting or expanding the rings or replacing some atoms in the ring with other atoms (heteroatoms). Domoprenate (INN) and oxandrolone (INN) are examples of analogues of this type. The family of analogues and derivatives preserving the basic structure of the described gonanes includes a large number of compounds used as hormone inhibitors and hormone antagonists (antihormones). Examples are the antiandrogen cyproterone (INN),

antigonadotrophin danazol (INN), and epostane (INN), which inhibits the production of progesterone. (c) Prostaglandin, thromboxane and leukotriene analogues may be obtained by substitution of atoms in the chain or by the formation or cleavage of rings. In tilsuprost (INN), a prostaglandin analogue, oxygen and carbon atoms have been replaced by nitrogen and sulphur atoms and one ring has been closed. (VI) Natural mixtures of hormones or their derivatives, or of steroids, having a hormonal effect (e.g., natural mixtures of corticosteroid hormones or of conjugated oestrogens). Mixtures or preparations specially obtained are excluded from this heading (generally heading 3003 or 3004). Releasing hormones (hormone-releasing factors), hormone inhibitors and hormone antagonists (anti-hormones) are also covered by this heading (see Note 8 to this Chapter). This heading also covers derivatives and structural analogues of hormones, provided that they are obtained on the basis of natural hormones or of synthetically produced ones, and that their mechanism of action is similar to that of hormones. A list of the products of this heading, arranged according to their chemical structure, is given below. This list is not exhaustive. List of compounds to be regarded as compounds of heading 2937 (*) (A) POLYPEPTIDE HORMONES, PROTEIN AND GLYCOPROTEIN HORMONES, THEIR DERIVATIVES AND STRUCTURAL ANALOGUES This group includes, inter alia: (1) Somatotropin, its derivatives and structural analogues. Somatotropin (growth hormone, GH, STH (somatotropic hormone)). A water-soluble protein which stimulates tissue growth and is involved in the regulation of other phases of protein metabolism. It is secreted by the somatotropic cells of the anterior lobe of the pituitary gland. Its secretion is regulated by a releasing factor (somatoliberin) and by a somatotropin inhibitor, somatostatin. Human growth hormone (hGH) is a single polypeptide chain of 191 amino acids, obtained mainly from recombinant DNA. This group also includes derivatives and analogues such as somatrem (INN) (methionyl-hGH), acetylated hGH, desamido-hGH and somnopor (INN), and antagonists such as pegvisomant (INN). (2) Insulin and its salts. Insulin is a polypeptide containing 51 amino-acid residues, formed in the islets of Langerhans of the pancreas in many animals. Human insulin may be extracted from the pancreas, obtained by modification of bovine or porcine insulin, or produced by biotechnology using bacteria or yeast to obtain recombinant human insulin. Insulin promotes the uptake of glucose and other nutrients by cells and their storage as glycogen or fat. Pure insulin is a white non-hygroscopic powder of amorphous structure or glistening crystals, soluble in water. Clinically, insulin is used in the treatment of diabetes mellitus. Insulin salts include insulin hydrochloride.

In the case of medicines having an international non-proprietary name or an international (modified) non-proprietary name published by the World Health Organization, this name is given first with the mark (INN) or (INNM), respectively.

(3) Corticotrophin (INN) (ACTH (adrenocorticotrophic hormone), adrenocorticotrophin). A water-soluble polypeptide. It stimulates increased production of steroids by the adrenal cortex. Giractide (INN) is an analogue of corticotrophin. (4) Lactogenic hormone (LTH, galactin, galactogenic hormone, luteotrophin, mammotrophin, prolactin). A polypeptide capable of crystallising. It increases the secretion of milk and influences the activity of the corpus luteum. (5) Thyrotrophin (INN) (thyrotrophic hormone, TSH (thyroid-stimulating hormone)). A glycoprotein regulating the action of the thyroid gland on the blood and the elimination of iodine from the body. It influences growth and secretion. (6) Follicle-stimulating hormone (FSH). A water-soluble glycoprotein. It activates sexual functions. (7) Luteinising hormone (LH, ICSH (interstitial cell-stimulating hormone), luteinostimulin). A water-soluble glycoprotein. It stimulates sexual functions by stimulating the secretion of steroids, ovulation and the development of interstitial cells. (8) Chorionic gonadotrophin (INN) (hCG (human chorionic gonadotrophin)). Formed in the placenta; a glycoprotein extracted from the urine of pregnant women. White crystals; relatively unstable in aqueous solution. It stimulates the maturation of follicles. (9) Serum gonadotrophin (INN) (equine serum gonadotrophin (eCG)). A gonad-stimulating glycoprotein formed in the placenta and endometrium of pregnant mares. Originally called pregnant mare serum gonadotrophin. (10) Oxytocin (INN) (α-hypophamine). A water-soluble polypeptide. Its principal action is the contraction of the uterus and the ejection of milk by the mammary glands. This group also includes analogues such as carbetocin (INN), demoxytocin (INN), etc. (11) Vasopressins: argipressin (INN), lypressin (INN), their derivatives and structural analogues. Vasopressins are polypeptides which raise blood pressure and promote the retention of water by the kidneys. This group also includes polypeptide analogues such as terlipressin (INN), desmopressin (INN), etc. (12) Calcitonin (INN) (TCA (thyrocalcitonin)). A hypocalcaemic and hypophosphataemic polypeptide. (13) Glucagon (INN) (HGF (hyperglycaemic-glycogenolytic factor)). A polypeptide capable of raising the concentration of glucose in the blood. (14) Thyroliberin (TRF, TRH). This polypeptide stimulates the secretion of thyrotrophin. (15) Gonadorelin (INN) (gonadoliberin, gonadotrophin-releasing hormone, LRF, GnRH). This polypeptide enhances the secretion of follicle-stimulating and luteinising hormones by the pituitary gland. This group also includes polypeptides analogous to buserelin (INN), goserelin (INN), fertirelin (INN), sermorelin (INN), etc. (16) Somatostatin (INN) (SS, SRIH, SRIF). This polypeptide suppresses the release of growth hormone and TSH by the pituitary gland and has a neurotropic action. (17) Atrial natriuretic hormone (ANH, ANF), a polypeptide hormone secreted by the atria of the heart. When the atrium is distended because of an increase in blood volume, the secretion of ANH is stimulated. ANH in turn increases the excretion of salt and water and reduces blood pressure.

(18) Endothelin, a polypeptide hormone secreted by the endothelial cells of all vessels. Although endothelin is released into the bloodstream, it acts locally in a paracrine manner, contracting the adjacent vascular smooth muscle and thereby raising blood pressure. (19) Inhibin and activin, hormones present in the tissues of the gonads. (20) Leptin, a polypeptide hormone produced by adipose tissue and believed to act on brain receptors to regulate body mass and fat deposition. This group also includes metreleptin (INN), a recombinant methionyl derivative of leptin, which has similar activity and is considered to be an analogue of leptin. (B) STEROID HORMONES, THEIR DERIVATIVES AND STRUCTURAL ANALOGUES (1) Corticosteroid hormones, secreted by the adrenal cortex, play an important role in the metabolic processes of the body. They are also called adrenocortical hormones or corticoids and are divided mainly into the following two groups according to their physiological action: (i) glucocorticoids, which regulate the metabolism of proteins and carbohydrates, and (ii) mineralocorticoids, which cause the retention of sodium and water in the body and accelerate the excretion of potassium. The properties of mineralocorticoids are used in the treatment of renal insufficiency and Addison's disease. This group also includes the following corticosteroid hormones, their derivatives and analogues: (a) cortisone (INN). A glucocorticoid which regulates the metabolism of proteins and carbohydrates and has a local anti-inflammatory action; (b) hydrocortisone (INN) (cortisol). A glucocorticoid with actions similar to those of cortisone; (c) prednisone (INN) (dehydrocortisone). A glucocorticoid. A derivative of cortisone; (d) prednisolone (INN) (dehydrohydrocortisone). A glucocorticoid. A derivative of hydrocortisone; (e) aldosterone (INN). A mineralocorticoid; (f) cortodoxone (INN). Certain hormone derivatives are modified in such a way that their corticosteroid activity is suppressed but their anti-inflammatory effect is pronounced; they are regarded as having a hormonal action. These include the basic derivatives of cortisone (INN), hydrocortisone (INN), prednisone (INN) and prednisolone (INN), which are used as anti-inflammatory and antirheumatic agents. (2) Halogenated derivatives of corticosteroid hormones are steroids in which a hydrogen atom, mainly in the 6- or 9-position of the gonane ring, has been replaced by a chlorine or fluorine atom (e.g., dexamethasone (INN)), which considerably enhances the glucocorticoid and anti-inflammatory action of the corticoids of which they are derivatives. These derivatives are often further modified and supplied in the form of esters, acetonides (e.g., fluocinolone acetonide (INN)), etc. (3) Oestrogens and progestins. These are the two principal groups of sex hormones, secreted by the male and female reproductive organs. They may also be obtained by synthesis. These hormones are also called progestins and gestagens. Oestrogens are the female sex hormones produced by the ovaries, the male gonads, the adrenal glands, the placenta and other steroid-

producing tissues. They are characterized by the ability to cause a strong sexual desire in female mammals. Estrogens are responsible for the development of female sexual characteristics and are used in the treatment of menopause or in the manufacture of contraceptives. These include the following estrogens, derivatives, and analogs: (a) estrone (INN). The main human estrogen; (b) estradiol (INN). Important natural estrogen; (c) estriol (INN). Natural estrogen; (d) ethinyl estradiol (INN). Important synthetic estrogen, active in oral use and used as the main estrogenic component in oral contraceptives; (e) mestaranol (INN). Simple ethinyl estradiol ether. It is used as an oral contraceptive. Progestins are a class of steroid hormones that got their name because of the progestogenic effects that are important in the occurrence and development of pregnancy. These female sex hormones are produced in the uterus when pregnancy occurs and to preserve pregnancy. Due to the fact that progestogens prevent ovulation, they are used as components of contraceptives. These include: (a) progesterone (INN). The main human progestin and intermediate in the biosynthesis of estrogens, androgens and corticosteroids. It is produced by the cells of the yellow body after the release of the egg and the adrenal glands, as well as the placento and male sex glands; (b) pregnandiol, a naturally occurring progestin with much less physiological activity than progesterone. (4) Other steroid hormones. Androgens, the main group of sex hormones not mentioned above, are produced mainly by the male sex glands and to a lesser extent by the ovaries, adrenal glands and placenta. Androgens are responsible for the development of male sexual characteristics. Androgens affect metabolism, that is, have an anabolic effect. Testosterone (INN) is one of the most important androgens. This also includes synthetic steroids used primarily to suppress or eliminate the action of hormones, such as antiestrogens, antiandrogens and antiprogestins (antiestagens). Steroid bottom antiprogestins are progestin antagonists that are used in the treatment of certain diseases. Examples of compounds of this group are onapristone (INN) and aglepristone (INN). Steroids, which occupy the most important place in international trade, are listed below. The compounds are listed alphabetically according to their short names, indicating their primary hormonal action. If there are two or more names, the one that is adopted in the International Nonproprietary Names for Pharmaceuticals (INN) published by the World Health Organization or in the International Nonproprietary Names Modified (INNM) is indicated. Chemical names are given in accordance with the IUPAC 1957 rules for the nomenclature of steroids. List of steroids used mainly due to their hormonal effects

Short name Chemical name Principal hormonal action ___________________________________________________ ______________ Adrenosterone androst-4-ene-3,11,17-trione Androgen Aldosterone (INN) 11β,21-dihydroxy-3,20-dioxopregn-4-en-18-al Corticosteroid Allylestrenol (INN) 17α-allyloestr-4-en-17β-ol Progestogen (No short name) 5α-androstane-3,17-dione Androgen – intermediate Androstanolone (INN) 17β-hydroxy-5α-androstan-3-one Androgen Androstenediols androst-5-ene-3β,17β-diol androst-5-ene-3β,17α-diol Anabolic agents – intermediates (No short name) androst-4-ene-3,17-dione Androgen – intermediate Androsterone 3α-hydroxy-5α-androstan-17-one Androgen Betamethasone (INN) 9α-fluoro-11β,17α,21-trihydroxy-16β-methylpregna-1,4-diene- 3,20-dione Corticosteroid Bolasterone (INN) 17β-hydroxy-7α,17α-dimethylandrost-4-en-3-one Anabolic agent Chlormadinone (INN) 6-chloro-17α-hydroxypregna-4,6-diene-3,20-dione Progestogen Chlorprednisone (INN) 6α-chloro-17α,21-dihydroxypregna-1,4-diene-3,11,20-trione Corticosteroid Clocortolone (INN) 9α-chloro-6α-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4- diene-3,20-dione Corticosteroid Clostebol (INN) 4-chloro-17β-hydroxyandrost-4-en-3-one Anabolic agent Corticosterone 11β,21-dihydroxypregn-4-ene-3,20-dione Corticosteroid

Cortisol - see Hydrocortisone Cortisone (INN) 17α,21-dihydroxypregne-4-en-3,11,20-trione

Corticosteroid 11-Dehydroxycorticosterone 21-hydroxypregn-4-en-3,11,20-trione Corticosteroid Deoxycorticosterone - see Deoxycorton Deoxycorton (INN) 21-hydroxypregn-4-en-3,20-dione

Corticosteroid Dexamethasone (INN) 9α-fluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4-diene- 3,20-dione Corticosteroid Dihydroandrosterone 5α-androstane-3α,17β-diol Androgen – intermediate Dydrogesterone (INN) 9β,10α-pregna-4,6-diene-3,20-dione Progestogen Equilenin 3-hydroxyoestra-1,3,5(10),6,8-pentaen-17-one Oestrogen Equilin 3-hydroxyoestra-1,3,5(10),7-tetraen-17-one Oestrogen Oestradiol (INN) oestra-1,3,5(10)-triene-3,17-β-diol Oestrogen Oestriol (INNM) oestra-1,3,5(10)-triene-3,16α,17β-triol Oestrogen Oestrone (INN) 3-hydroxyoestra-1,3,5(10)-trien-17-one Oestrogen Ethinyloestradiol (INN) 17α-ethynyloestra-1,3,5(10)-triene-3,17β-diol Oestrogen Ethisterone (INN) 17α-ethynyl-17β-hydroxyandrost-4-en-3-one Progestogen Ethyloestrenol (INN) 17α-ethyloestr-4-en-17β-ol Anabolic agent Etynodiol (INN) 17α-ethynyloestr-4-ene-3β,17β-diol Progestogen Fludrocortisone (INN) 9α-fluoro-11β,17α,21-trihydroxypregn-4-ene-3,20-dione Corticosteroid

Flumetasone (INN) 6α,9α-difluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4- diene-3,20-dione Corticosteroid Fluocinolone (INNM) 6α,9α-difluoro-11β,16α,17α,21-tetrahydroxypregna-1,4-diene- 3,20-dione Corticosteroid Fluocortolone (INN) 6α-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4-diene-3,20- dione Corticosteroid Fluorometholone (INN) 9α-fluoro-11β,17α-dihydroxy-6α-methylpregna-1,4-diene-3,20- dione Corticosteroid 9α-Fluoroprednisolone 9α-fluoro-11β,17α,21-trihydroxypregna-1,4-diene-3,20-dione Corticosteroid Fluoxymesterone (INN) 9α-fluoro-11β,17β-dihydroxy-17α-methylandrost-4-en-3-one Androgen Fluprednidene (INN) 9α-fluoro-11β,17α,21-trihydroxy-16-methylenepregna-1,4-diene- 3,20-dione Corticosteroid Fluprednisolone (INN) 6α-fluoro-11β,17α,21-trihydroxypregna-1,4-diene-3,20-dione Corticosteroid Flurandrenolone 6α-fluoro-11β,16α,17α,21-tetrahydroxypregn-4-ene-3,20-dione Corticosteroid Formocortal (INN) 3-(2-chloroethoxy)-9α-fluoro-6-formyl-11β,21-dihydroxy- 16α,17-isopropylidenedioxypregna-3,5-dien-20-one-21-acetate Corticosteroid Gestonorone (INNM) 17β-ethyl-17α-hydroxyoestr-4-ene-3,20-dione Progestogen Hydrocortisone (INN) 11β,17α,21-trihydroxypregn-4-ene-3,20-dione Corticosteroid Hydroxyprogesterone (INN) 17α-hydroxypregn-4-ene-3,20-dione Progestogen Lynestrenol (INN) 17α-ethynyloestr-4-en-17β-ol Progestogen Medroxyprogesterone (INN) 17α-hydroxy-6α-methylpregn-4-ene-3,20-dione Progestogen

Megestrol (INN) 17α-hydroxy-6-methylpregna-4,6-diene-3,20-dione Progestogen Mestanolone (INN) 17β-hydroxy-17α-methyl-5α-androstan-3-one Anabolic agent Mesterolone (INN) 17β-hydroxy-1α-methyl-5α-androstan-3-one Androgen Mestranol (INN) 17α-ethynyl-3-methoxyoestra-1,3,5(10)-trien-17β-ol Oestrogen Metandienone (INN) 17β-hydroxy-17α-methylandrosta-1,4-dien-3-one Anabolic agent Metenolone (INN) 17β-hydroxy-1-methyl-5α-androstan-1-en-3-one Anabolic agent Methandriol (INN) 17α-methylandrost-5-ene-3β,17β-diol Anabolic agent 2-Methylhydrocortisone 11β,17α,21-trihydroxy-2β-methylpregn-4-ene-3,20-dione Corticosteroid 6α-Methylhydrocortisone 11β,17α,21-trihydroxy-6α-methylpregn-4-ene-3,20-dione Corticosteroid Methylnortestosterone 17β-hydroxy-17α-methyloestr-4-en-3-one Progestogen 17α-Methyloestradiol 17α-methyloestra-1,3,5(10)-triene-3,17β-diol Oestrogen Methylprednisolone (INN) 11β,17α,21-trihydroxy-6α-methylpregna-1,4-diene-3,20-dione Corticosteroid Methyltestosterone (INN) 17β-hydroxy-17α-methylandrost-4-en-3-one Androgen Nandrolone (INN) 17β-hydroxyoestr-4-en-3-one Anabolic agent Norethandrolone (INN) 17α-ethyl-17β-hydroxyoestr-4-en-3-one Anabolic agent Norethisterone (INN) 17α-ethynyl-17β-hydroxyoestr-4-en-3-one Progestogen Noretynodrel (INN) 17α-ethynyl-17β-hydroxyoestr-5(10)-en-3-one Progestogen

Norgestrel (INN) 13β-ethyl-17α-ethynyl-17β-hydroxygon-4-en-3-one Progestogen Normethandrone – see Methylnortestosterone Nortestosterone – see Nandrolone Oxabolone (INNM) 4,17β-dihydroxyoestr-4-en-3-one Anabolic agent Oxymesterone (INN) 4,17β-dihydroxy-17α-methylandrost-4-en-3-one Anabolic agent Oxymetholone (INN) 17β-hydroxy-2-hydroxymethylene-17α -methyl-5α-androstan-3- one Anabolic agent Paramethasone (INN) 6α-fluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4-diene- 3,20-dione Corticosteroid Prasterone (INN) 3β-hydroxyandrost-5-en-17-one Androgen Prednisolone (INN) 11β,17α,21-trihydroxypregna-1,4-diene-3,20-dione Corticosteroid Prednisone (INN) 17α,21-dihydroxypregna-1,4-diene-3,11,20-trione Corticosteroid Prednylidene (INN) 11β,17α,21-trihydroxy-16-methylenepregna-1,4-diene-3,20-dione Corticosteroid Pregnenolone (INN) 3β-hydroxypregn-5-en-20-one Corticosteroid Progesterone (INN) pregn-4-ene-3,20-dione Progestogen Stanolone – see Androstanolone Testosterone (INN) 17β-hydroxyandrost-4-en-3-one Androgen Tiomesterone (INN) 1α,7α-di(acetylthio)-17β-hydroxy-17α-methylandrost-4-en-3- one Anabolic agent Triamcinolone (INN) 9α-fluoro-11β,16α,17α,21-tetrahydroxypregna-1,4-diene-3,20- dione Corticosteroid

(C) Prostaglandins, tromboxans and leukotrienes, their derivative and structural analogues

These products are derivatives of arachidonic acid. (1) Prostaglandins. The most important derivatives of arachidonic acid are the prostaglandins, endogenous substances which act in small doses like hormones and which have the basic structure of prostanoic acid. Prostaglandins affect the regulation of blood flow, renal function and the endocrine system (e.g., they reduce the production of progesterone by the corpus luteum); they also stimulate the contraction of smooth muscle or the dilation of blood vessels, prevent platelet aggregation and regulate gastric secretion. This group includes the following prostaglandins, derivatives and analogues: (a) Alprostadil (INN) (prostaglandin E1). The principal prostaglandin, crystallised from biological extracts. It is used as a vasodilator. It also stimulates the release of erythropoietin from the renal cortex and inhibits blood platelet aggregation; (b) Alfaprostol (INN). A synthetic prostaglandin analogue used for the treatment of infertility in mares; (c) Tilsuprost (INN). A prostaglandin analogue in which the oxygen and carbon atoms in the closed ring are replaced by nitrogen and sulphur atoms. A synthetic prostaglandin and an agonist of the prostaglandin receptor. This category also includes other synthetic products, such as prostalene (INN), dinoprost (INN), etc., which retain the basic structure of the natural compounds and have a similar physiological activity. (2) Thromboxanes and leukotrienes. Thromboxanes and leukotrienes, like the prostaglandins, are synthesised in cells from arachidonic acid; although their action is similar to that of the prostaglandins and their structures are very similar, they do not contain the basic structure of prostanoic acid. Thromboxanes are formed by biosynthesis from prostaglandins. They cause platelet aggregation and arterial constriction and are important regulators of the action of polyunsaturated fatty acids. Leukotrienes owe their name to their formation in leucocytes and to their conjugated triene structure. They are powerful bronchoconstrictors and play an important role in hypersensitivity reactions. (a) Thromboxane B2. A vasoconstrictor and bronchoconstricting agent; it causes blood platelet aggregation. (b) Leukotriene C4. It is known to be 100 to 1000 times more potent than histamine or prostaglandins in its effect on airway patency in the lungs. (D) OTHER HORMONES This group covers other hormones whose structure differs from that of the hormones described above, for example, melatonin, which is formed in the pineal gland and may be regarded as an indole derivative. The heading includes the following other hormones: (1) Catecholamine hormones, their derivatives and structural analogues. This category of compounds covers the hormones present in the adrenal medulla. (a) Epinephrine (INN) (adrenaline or (-)-3,4-dihydroxy-α-

[(methylamino)methyl]benzyl alcohol and racepinephrine (INN) ((±)-3,4-dihydroxy-α-[(methylamino)methyl]benzyl alcohol). The structure of these hormones corresponds to the chemical name 1 -(3,4-dihydroxyphenyl) - 2-methylaminoethanol. Epinephrine is a light brown or almost white crystalline powder sensitive to the action of light; little soluble in water and organic solvents. It can be obtained from the adrenal glands of horses, but it is mainly obtained by synthesis. The hormone that increases pressure stimulates the activity of the sympathetic nervous system, increases the content of blood cells and sugar in the blood; it also has a strong vasoconstrictor effect.

(b) Norepinephrine (INN) (levarterenol, noradrenaline or (–)-2-amino-1-(3,4- dihydroxyphenyl)ethanol). Norepinephrine exists in the form of white crystals, soluble in water. In its physiological activity it occupies an intermediate position between adrenaline and ephedrine. (2) Amino-acid derivatives. (a) Levothyroxine (INNM) and DL-thyroxine (3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5- diiodophenyl]alanine or 3,5,3',5' -tetraiodothyronine). Thyroxine is extracted from thyroid glands or produced synthetically. It is an aromatic amino acid; it exists in the form of white or yellowish crystals, insoluble in water or in most of the common solvents. It increases the basal metabolic rate and oxygen consumption, acts on the sympathetic system, regulates the action of proteins and fats and remedies iodine deficiency in the body; it is used in the treatment of goitre and cretinism. The L-isomer is the active form. The sodium salt is a white powder, slightly soluble in water, with a similar action. (b) Liothyronine (INN) and ratironine (INN) (DL-3,5,3'-triiodothyronine) (3-[4-(4-hydroxy-3- iodophenoxy)-3,5-diiodophenyl]alanine). Triiodothyronine is also extracted from the thyroid gland; its physiological activity is higher than that of thyroxine. EXCLUSIONS This heading does not cover: (1) Products which have no hormonal action but have a hormone-like structure: (a) androst-5-ene-3α,17α-diol, androst-5-ene-3α,17β-diol (heading 2906) and their diacetates (heading 2915); (b) adrenalone (INN) (3',4'-dihydroxy-2-methylaminoacetophenone) (heading 2922); (c) the following products, which fall in heading 2922: (i) 2-amino-1-(3,4-dihydroxyphenyl)butan-1-ol; (ii) corbadrine (INN) (2-amino-1-(3,4-dihydroxyphenyl)propan-1-ol, 3,4-dihydroxynorephedrine, homoarterenol); (iii) deoxyepinephrine (deoxyadrenaline, 1-(3,4-dihydroxyphenyl)-2-methylaminoethane, epinine); (iv) 3',4'-dihydroxy-2-ethylaminoacetophenone (4-ethylaminoacetylcatechol); (v) 1-(3,4-dihydroxyphenyl)-2-methylaminopropan-1-ol (3,4-dihydroxyephedrine); (vi) (–)-N-methylepinephrine ((–)-1-(3,4-dihydroxyphenyl)-2-dimethylaminoethanol, methadren, (–)-N-methyladrenaline). (2) Compounds which have a hormonal action but do not have a hormone-like structure:

(a) dienestrol (INN) (3,4-bis(p-hydroxyphenyl)hexa-2,4-diene) (heading 2907); (b) hexestrol (INN) (3,4-bis(p-hydroxyphenyl)hexane) (heading 2907); (c) diethylstilbestrol (INN) (trans-3,4-bis(p-hydroxyphenyl)hex-3-ene) (heading 2907), its dimethyl ether (heading 2909), its dipropionate (heading 2915) and its furoate (heading 2932); (d) clomifene (INN) (anti-oestrogen) (heading 2922); (e) tamoxifen (INN) (anti-oestrogen) (heading 2922); (f) flutamide (INN) (anti-androgen) (heading 2924); (g) endothelin antagonists, such as darusentan (INN) (heading 2933), atrasentan (INN) (heading 2934) and sitaxentan (INN) (heading 2935). (3) Natural substances which have a hormonal action but are not produced by the human or animal body: (a) zearalenone, an anabolic agent (heading 2932); (b) asperlicin, a cholecystokinin antagonist (heading 2933). (4) The following compounds, which are sometimes regarded as hormones but which do not in fact have a hormonal action: (a) cystine, cysteine (INN) and their hydrochlorides (heading 2930); (b) methionine and its calcium salts (heading 2930); (c) neurotransmitters and neuromodulators, such as sepranolone (INN) (heading 2914), dopamine (heading 2922), acetylcholine (heading 2923), serotonin (5-hydroxytryptamine or 5-hydroxy-3-(β-aminoethyl)indole) (heading 2933), histamine (heading 2933) and related products such as agonists and antagonists of their receptors; (d) leukaemia inhibitory factor (human) and the growth factor emfilermin (INN) (heading 2933) and the fibroblast growth factor repifermin (INN) (heading 2933); (e) N-methyl-D-aspartic acid receptor antagonists, such as lanicemine (INN) (heading 2933) and nebostinel (INN) (heading 2924); (f) heparin (heading 3001); (g) modified immunological products (heading 3002). (5) Plant growth regulators (e.g., phytohormones), natural or synthetic, which are classified: (A) If unmixed and not put up for retail sale, according to their chemical constitution, for example: (a) α-naphthylacetic acid and its sodium salt (heading 2916); (b) 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-T (ISO) (2,4,5-trichlorophenoxyacetic acid) and 4-chloro-2-methylphenoxyacetic acid (MCPA) (heading 2918); (c) β-indolylacetic acid and its sodium salt (heading 2933). (B) If put up in forms or packings for retail sale or as preparations or articles, in heading 3808. (6) Thromboxane and leukotriene antagonists, which are classified according to their structure (e.g., seratrodast (INN) (heading 2918) and montelukast (INN) (heading 2933)). (7) Tumour necrosis factor antagonists, such as ataquimast (INN) (heading 2933). (8) Immunological products of heading 3002. (9) Medicaments of heading 3003 or 3004, in particular "retard insulin" (zinc-insulin, protamine-zinc insulin, globin-insulin, zinc-globin insulin, histone-insulin). Subheading Explanatory Notes. Subheadings 2937 11 to 2937 19

These subheadings include peptide hormones containing two or more amino acids. Sub-Chapter XII Glycosides and Alkaloids, Natural or Synthesized, Their Salts, Simple and Complex Ethers and Other Produced General Provisions In this sub-Chapter, the term "derivatives" means chemical compounds which can be obtained from the parent compound of the heading concerned and which retain the essential properties of the parent compound, including its basic structure.

Notes

Machine translation. The original is the Russian text of the EAEU tariff, and customs goes by it; this translation is for understanding only and has no legal force.

1. Unless otherwise specified in the context, the headings of this chapter include only:

(a) individual organic compounds of a particular chemical composition, whether or not containing impurities;

(b) mixtures of two or more isomers of the same organic compound (containing or not containing impurities), except for mixtures of isomers of acyclic hydrocarbons (but not stereoisomers), saturated or unsaturated (Chapter 27);

(c) products of headings 2936 to 2939 or simple esters of sugars, acetals of sugars, esters of sugars and their salts, of heading 2940, or products of heading 2941, whether chemically defined or indefinite;

(d) products referred to in points (a), (b) or (c) above dissolved in water;

(e) products referred to in points (a), (b) or (c) above dissolved in other solvents, provided that dissolution is the usual and necessary method used solely for the preservation or transportation of these products, and that the solvent does not render the product suitable for a specific application other than conventional use;

(f) products referred to in points (a), (b), (c), (d) or (e) above, with the addition of a stabilizing substance (including an anti-traceability agent) necessary for their preservation or transport;

(g) products referred to in points (a), (b), (c), (d), (e) or (f) above, with the addition of an anti-dust agent or a coloring or fragrant substance or emetic to facilitate their identification or for safety purposes, provided that these additives do not make the product suitable for a specific use other than traditional use;

(h) the following products diluted to a standard concentration for the production of azo dyes: diazonium salts, substances reacting with these salts, diazotizing amines and their salts.

2. This group does not include:

(a) the goods of heading 1504 or of raw glycerol of heading 1520;

(b) ethyl alcohol (heading 2207 or 2208);

(c) methane or propane (heading 2711);

(d) the carbon compounds referred to in Note 2 to Chapter 28;

(e) immunological products of heading 3002;

(f) urea (heading 3102 or 3105);

(g) dyes of vegetable or animal origin (heading 3203), synthetic organic dyes, synthetic organic products used as optical bleaches or phosphors (heading 3204), or dyes or other dyes packaged in molds or packages for retail sale (heading 3212);

(h) enzymes (heading 3507);

(ij) metaldehyde, hexamethylenetetramine or similar substances, packaged in moulds (e.g. tablets, sticks or similar forms) intended for use as fuel, or liquid or liquefied gaseous fuel in containers of not more than 300 cm in capacity, used for filling or refilling cigarette or similar lighters (heading 3606);

(k) products supplied as fire extinguishing charges or grenades for extinguishing fires of heading 3813; ink stain removal preparations packaged for retail sale of heading 3824; or

(l) optical elements, for example of ethylenediamintartrate (heading 9001).

3. Goods which may be included in two or more headings of this Chapter are classified in the heading, the latter in ascending order of the codes in this Chapter of the Nomenclature.

4. For the purposes of headings 2904 to 2906, 2908 to 2911 and 2913 to 2920, any reference to halogenated, sulfonated, nitrated or nitrosed derivatives also applies to mixed derivatives such as sulfohalogenated, nitrohalogenated, nitrosulfonated or nitrosulfohalogenated derivatives.

For the purposes of heading 2929, nitrogen or nitrozo groups are not regarded as nitrogen-containing functional groups.

For the purposes of headings 2911, 2912, 2914, 2918 and 2922, the term “oxygen-containing functional group” means that the characteristic organic oxygen-containing groups of these headings are limited to the oxygen-containing functional groups referred to in headings 2905 to 2920.

5. (A) Esters of organic compounds with acidic functional groups of subgroups I to VII with organic compounds of the same subgroups shall be included with that of them which falls in the heading last in ascending order of codes in these subgroups of the Nomenclature.

(B) Ethyl alcohol esters with organic compounds with acid functional groups of subgroups I to VII are to be classified in the same headings as the corresponding organic compounds with acid functional groups.

(C) Subject to note 1 to section VI and note 2 to chapter 28:

(1) Inorganic salts of organic compounds, such as compounds with acidic, phenolic or enolic functional groups, or organic bases of subgroups I to X or heading 2942, are to be classified in the headings for organic compounds;

(2) salts resulting from chemical reactions between organic compounds of subgroups I to X or heading 2942 are to be classified in the heading for the base or acid (including compounds with phenolic or enolic functional groups) from which these salts are formed, the latter in ascending order of the codes in the group; and

(3) Coordinating or complex compounds, other than substances of sub-group XI or heading 2941, are classified in the heading last in ascending order of the codes of Chapter 29, among those suitable for fragments formed by the "splitting" of all metal bonds other than metal-carbon bonds.

(D) Metal alcohols are to be classified in the same heading as the alcohols concerned, with the exception of ethanol (heading 2905).

(E) Carboxylic acid halides are to be classified in the same heading as the corresponding acids.

6. The compounds of headings 2930 and 2931 are organic compounds whose molecules, in addition to hydrogen, oxygen or nitrogen atoms, contain atoms of other nonmetals or metals (such as sulfur, arsenic or lead) directly bound to carbon atoms.

Headings 2930 (organic sulphur compounds) and 2931 (other organo-inorganic compounds) do not include sulfonated or halogenated derivatives (including complex derivatives) which, in addition to hydrogen, oxygen and nitrogen, have only directly carbon-related sulphur or halogen atoms giving them the properties of sulfonated or halogenated derivatives (or complex derivatives).

7. Headings 2932 to 2934 do not include three-membered ring epoxides, ketone peroxides, cyclic polymers of aldehydes or thioaldehydes, anhydrides of polybasic carboxylic acids, cyclic esters of polyalcohols or phenols with polybasic acids or imides of polybasic acids.

These provisions are applicable only if heteroatom cycles are formed only as a result of the cyclization reaction or as a result of the reactions mentioned above.

8. In heading 2937:

(a) the term “hormones” covers release hormones or factors that stimulate hormone secretion, hormone inhibitors and hormone antagonists (antihormones);

(b) the term “mainly used as hormones” applies not only to hormone derivatives and their structural analogues used principally for hormonal action, but also to such derivatives and structural analogues as are used principally as intermediates in the synthesis of substances of this heading.

Subheading notes

English text as published in Annex I to Regulation (EU) 2021/1832 (Combined Nomenclature). The EAEU tariff and the EU nomenclature copy these notes from the same convention. For a Russian declaration the binding version is the Russian one: Annex to Decision No 80 of the EEC Council of 14 September 2021.

1. Within any one heading of this chapter, derivatives of a chemical compound (or group of chemical compounds) are to be classified in the same subheading as that compound (or group of compounds), provided that they are not more specifically covered by any other subheading and that there is no residual subheading named ‘Other’ in the series of subheadings concerned.

2. Note 3 to Chapter 29 does not apply to the subheadings of this chapter.

Additional notes of the Eurasian Economic Union

Machine translation. The original is the Russian text of the EAEU tariff, and customs goes by it; this translation is for understanding only and has no legal force.

1. Subheading 2901 10 000 1 covers ethane, butane and isobutane in the form of separate isomers of a purity of 95% or more. This percentage of compounds is calculated respectively by volume for gaseous products or by weight for liquefied products. Ethane, butane and isobutane having a lower degree of purity fall in heading 2711.

2. Subheading 2901 10 000 2 covers pentane and isopentane as separate isomers of a purity of 95 % or more by weight.