WO2018095209A1 - 促进胃肠系统动力的复合维生素组合物 - Google Patents

促进胃肠系统动力的复合维生素组合物 Download PDF

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WO2018095209A1
WO2018095209A1 PCT/CN2017/109280 CN2017109280W WO2018095209A1 WO 2018095209 A1 WO2018095209 A1 WO 2018095209A1 CN 2017109280 W CN2017109280 W CN 2017109280W WO 2018095209 A1 WO2018095209 A1 WO 2018095209A1
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vitamin
parts
group
biotin
acid
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PCT/CN2017/109280
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English (en)
French (fr)
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周明东
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上海泽生科技开发股份有限公司
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Priority to CN201780072139.9A priority Critical patent/CN110022882A/zh
Priority to AU2017364583A priority patent/AU2017364583B2/en
Priority to JP2019547749A priority patent/JP2020503373A/ja
Priority to EP17873082.6A priority patent/EP3545960A4/en
Priority to US16/462,510 priority patent/US11351171B2/en
Priority to BR112019010564A priority patent/BR112019010564A2/pt
Priority to CA3043648A priority patent/CA3043648A1/en
Publication of WO2018095209A1 publication Critical patent/WO2018095209A1/zh
Priority to US17/353,558 priority patent/US11759463B2/en
Priority to AU2023203550A priority patent/AU2023203550A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents

Definitions

  • the present invention relates to a vitamin B, C composition, and more particularly to a multivitamin B, C composition that promotes gastrointestinal system motility.
  • the composition is useful for preventing and/or treating a condition or disease associated with gastrointestinal motility.
  • Gastrointestinal motility is a coordinated neuromuscular process that delivers nutrients through the digestive system. May be involved in gastroesophageal reflux disease, gastroparesis (eg, diabetic and postoperative gastroparesis), irritable bowel syndrome (IBS), intestinal obstruction, and constipation (eg, functional or drug-induced constipation)
  • gastroparesis eg, diabetic and postoperative gastroparesis
  • IBS irritable bowel syndrome
  • constipation eg, functional or drug-induced constipation
  • gastrointestinal motility disorders are easy to lead to IBS.
  • the current drugs for the treatment of gastrointestinal motility are metoclopramide, domperidone and itopride.
  • metoclopramide the drug is a dopamine receptor blocker with strong central vomiting and gastrointestinal stimulatory effects.
  • the drug can inhibit the relaxation of gastric smooth muscle, increase the response of gastrointestinal smooth muscle to cholinergic, accelerate gastric emptying, and increase the phase activity of gastric antrum.
  • the drug also has the effect of stimulating the release of prolactin.
  • the side effects of metoclopramide are more common with lethargy, irritability, and fatigue.
  • the drug may cause symptoms of Parkinson's disease due to blockade of dopamine receptors in large doses or long-term use.
  • Domperidone is a peripheral dopamine receptor antagonist that promotes normal motility and tension of the upper gastrointestinal tract, promotes gastric emptying, increases gastric antrum and duodenal bowel movement, coordinates pyloric contraction, and can also Enhance the peristalsis of the esophagus and the tension of the lower esophageal sphincter. Because of its poor permeability to the blood-brain barrier, it has almost no antagonistic effect on dopamine receptors in the brain. There are reports of seizures caused by large-dose intravenous injections abroad (there is no such preparation in China), but this drug is a powerful prolactin. Hormone release drugs may cause menstrual disorders.
  • Itobili has the dual effects of dopamine receptor blockade and acetylcholinesterase inhibition, which enhances gastric and duodenal movement by stimulating endogenous acetylcholine release and inhibiting its hydrolysis, and promotes gastric emptying. Moderate antiemetic effect. This medicine should be used with caution in elderly or elderly patients.
  • Vitamin B is a water-soluble vitamin, mostly coenzyme, involved in the metabolism of sugar, protein and fat in the body.
  • Vitamin B1 can promote gastrointestinal motility and increase appetite. Vitamin B1 inhibits the hydrolysis of acetylcholine by cholinesterase. When B1 is deficient, the activity of the enzyme is increased, and the hydrolysis of acetylcholine is accelerated. Acetylcholine is an important substance that transmits nerve impulses. When it is lacking, it can cause nerve conduction disorder, especially affecting nerve conduction in the gastrointestinal tract, glands, etc., causing slow gastrointestinal motility, abdominal distension, decreased secretion of digestive glands, and reduced appetite. .
  • Vitamin B2 is a component of the luteinase excipients in the body. It can be converted into flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), both important coenzymes for tissue respiration, acting as hydrogen in the enzyme system, involved in sugar, protein, fat metabolism, and Can maintain normal visual function.
  • vitamin B2 activates vitamin B6, which converts tryptophan to niacin, which may be related to maintaining the integrity of red blood cells. It maintains and improves the health of epithelial tissues such as the digestive tract mucosa.
  • the mucosal layer of the human body cavity will have problems, causing mucosal lesions and enhancing the carcinogenic effect of chemical carcinogens. Therefore, vitamin B2 can prevent cancer.
  • Vitamin B3 constitutes a coenzyme for dehydrogenase in the body. It is the most needed B vitamins in the human body. It is not only a vitamin that maintains the health of the digestive system, but also reduces gastrointestinal disorders. Niacin is converted into nicotinamide in human body. Niacinamide is a component of coenzyme I and coenzyme II, which participates in lipid metabolism in the body, oxidation process of tissue respiration and anaerobic decomposition of carbohydrates. It can promote the health of the digestive system, reduce gastrointestinal disorders, and effectively alleviate constipation symptoms. If it is lacking, it can cause angular cheilitis, glossitis, diarrhea, etc.
  • Diarrhea is a typical symptom of this disease. It is often caused by constipation in the early stage, and then due to intestinal wall, digestive gland, intestinal wall and mucosa, atrophy of villi and enteritis. There are often diarrhea, the stool is watery or mushy, the amount is too much and there is stench, but also can bring blood, such as the lesion close to the anus can appear in the rush and then heavy. Diarrhea is often severe and refractory and can be combined with malabsorption.
  • vitamin B5 pantothenic acid
  • coenzyme A is an acyl carrier in the body and is involved in the metabolism of sugar, fat and protein. They work synergistically to regulate metabolism, maintain skin and muscle health, enhance immune and nervous system function, promote cell growth and division (including promoting red blood cell production and preventing anemia).
  • the symptoms of vitamin B5 deficiency are loss of appetite, indigestion, and prone to duodenal ulcer.
  • Vitamin B6 includes three kinds of pyridoxine, pyridoxal and pyridoxamine, which can be converted into each other. In vivo, ATP is converted into a coenzyme of various physiologically active enzymes by enzymatic action, thereby participating in various metabolic functions of amino acids and fats. In combination with vitamin B1, it has a strong analgesic effect. Vitamin B12 can enhance the analgesic effect of the combination of both, and alleviate the pain caused by peripheral nerve diseases and spinal cord diseases. Studies have reported that intravenous infusion of vitamin B6 and azithromycin can reduce the side effects of azithromycin on the gastrointestinal tract. Mainly in the body's blood, muscles, nerves, skin and so on.
  • Vitamin B6 deficiency damages cells and affects humoral immune function. Vitamin B6 can increase immunity, reduce carcinogens in the body, and have certain anti-cancer effects.
  • Vitamin B7 also known as vitamin H, biotin, coenzyme R, participates in the metabolism of fatty acids and carbohydrates in the body; promotes protein synthesis; also participates in the metabolism of vitamin B12, folic acid and pantothenic acid; promotes urea synthesis and excretion. Enhance the body's immune response and infection resistance, stabilize the lysosomal membrane of normal tissues, maintain the body's humoral immunity, cellular immunity and affect the secretion of a series of cytokines, improve the body's immune function. Reduce the symptoms of perianal eczema and itching.
  • the biotin side chain carboxyl group can be attached to the lysine residue of the enzyme via an amide bond. Biotin is a carboxyl carrier and is also involved in the metabolism of vitamin B12, folic acid, and pantothenic acid.
  • Vitamin B9 (folic acid), a water-soluble B vitamin consisting of pteridine, p-aminobenzoic acid and glutamic acid residues.
  • Tetrahydrofolic acid is a carrier for the transfer of "monocarbon groups" in vivo.
  • a "monocarbon group” can be attached to the 5- or 10-position carbon atom of tetrahydrofolate, and is mainly involved in the synthesis and conversion of purine nucleotides and pyrimidine nucleotides.
  • folic acid for women are widely noticed by the medical community, and should be supplemented by pregnant and lactating women to prevent rectal cancer and heart disease. It has also been found to prevent free radical damage to chromosomes, and humans such as the lack of folic acid can cause macrocytic anemia and leukopenia.
  • Deoxyadenosylcobalamin is a major form of vitamin B12 in the body. It is a red compound containing cobalt. It needs to be converted to methylcobalamin and coenzyme B12 to be active. Vitamin B12 and folic acid play an important role in DNA synthesis. In addition, vitamin B12 also plays an important role in the maturation of red blood cells and the normal maintenance of the nervous system. It is often associated with the action of folic acid. Folic acid has various forms of sputum in cells. Studies have suggested that folic acid can interfere with the occurrence of gastrointestinal cancer. Folic acid can treat atrophic gastritis and improve the pathology of gastric mucosa.
  • Hydrocholine tartrate promotes the conversion of phospholipids, accelerates the functioning of fats, and acts as a choleretic agent; inositol promotes cell metabolism, promotes development, and increases appetite.
  • Para-aminobenzoic acid (PABA) is actually a component of folic acid. Its role in the body is coenzyme, which works in conjunction with folic acid to promote protein metabolism and blood cell production.
  • Vitamin C also known as ascorbic acid, is one of the antioxidant vitamins. It is involved in the hydroxylation reaction in the body and is necessary for the formation of bone, tooth, connective tissue and non-epithelial cells. It can maintain the normal teeth, bones and blood vessels. Function to increase resistance to disease. According to relevant information, vitamin C has different degrees of deficiency in various populations. When there are some minor problems in the body, you should promptly supplement the appropriate amount of vitamins and minerals to improve nutritional deficiencies, especially in middle-aged and elderly people. Vitamins have a preventive effect on many diseases, and many diseases may be more or less related to the lack of vitamin C. In addition, vitamin C can be combined with many other drugs to treat certain diseases. Vitamin C is an antioxidant that protects the body from free radicals.
  • Vitamin C is also a coenzyme. Many studies have shown that vitamin C can block the synthesis of carcinogen N-nitroso compounds, preventing the formation of carcinogenic ammonium nitrite in salted, stained and smoked foods containing nitrite (same as bacon and sausage). Cancer, especially for rectal and colon cancer, has a better preventive effect. At the same time, it has the effect of softening the anorectal blood vessels and increasing the anorectal elasticity. VC is easily destroyed by heat or oxidant, especially light, trace heavy metals and fluorescent substances, which promotes its oxidation, which makes VC widely limited in application.
  • vitamin C including metal salts of VC, esters of VC and various acids, and compounds of VC and saccharides
  • VC instability can overcome the disadvantages of VC instability and better play the role of VC.
  • Physiological function include vitamin C (L-ascorbic acid), vitamin C sodium (L-ascorbate), vitamin C phosphate magnesium, vitamin C polyphosphate, vitamin C palmitate, vitamin C stearate, vitamin C glucose. Compounds, etc.
  • vitamin B is an important coenzyme involved in human energy metabolism, and vitamin C can promote the body's absorption of vitamin B members.
  • Multivitamins B and C enhance the body's energy metabolism and provide more energy to the gastrointestinal tract to improve functional dyspepsia caused by gastrointestinal motility. This increase in energy metabolism includes assisting carbohydrates and fats in releasing energy, breaking down amino acids, and delivering nutrient-containing oxygen and energy to the entire body.
  • Multivitamin BC will likely become a new drug or health food with a high safety to promote gastrointestinal system power, but by now So far, there is no evidence to prove that vitamin B and C promote the gastrointestinal system, especially in the pathological state, vitamin B, C treatment and regulation of gastrointestinal motility disorders.
  • the selection and compatibility of vitamin B components is essential for the preparation of drugs or health foods for treating or regulating gastrointestinal motility disorders.
  • the present invention relates to a method of promoting gastrointestinal system motility in a subject in need thereof, wherein the subject has a gastrointestinal system disorder (i.e., a disorder, a condition, a symptom, or a dysfunction caused by a drug or surgery).
  • the method comprises administering to a subject in need thereof a therapeutically effective amount of a vitamin B and vitamin C family composition.
  • vitamins referred to in the present invention include their corresponding analogs or derivatives, such as vitamin B1 means thiamine or an analogue or derivative thereof; vitamin B2 means riboflavin or an analogue or derivative thereof; vitamin B3 Means niacin or an analogue or derivative thereof; vitamin B5 means pantothenic acid or an analogue or derivative thereof; vitamin B6 means pyridoxine or an analogue or derivative thereof; vitamin B7 is biotin or its analogue or Derivative; vitamin B9 means folic acid or an analogue or derivative thereof; vitamin B12 means cyanocobalamin or an analogue or derivative thereof; vitamin C means ascorbic acid or an analogue or derivative thereof; and the like.
  • vitamin B1 means thiamine or an analogue or derivative thereof
  • vitamin B2 means riboflavin or an analogue or derivative thereof
  • vitamin B3 Means niacin or an analogue or derivative thereof
  • vitamin B5 means pantothenic acid or an analogue
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, A composition of vitamin C.
  • the multivitamin BC composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid , a combination of biotin, vitamin C, hydrogen choline tartrate, inositol.
  • the vitamin B group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, vitamins.
  • the invention provides a composition comprising an effective amount of a vitamin B family, a vitamin C family composition, and a pharmaceutically acceptable carrier.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, Vitamin C and a pharmaceutically acceptable carrier.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid, Biotin, vitamin C, hydrogencholine tartrate, inositol, and a pharmaceutically acceptable carrier.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, vitamins. B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol, p-aminobenzoic acid, and a pharmaceutically acceptable carrier.
  • vitamin B1 thiamine
  • vitamin B2 riboflavin
  • vitamin B3 nicotinic acid
  • vitamin B5 pantothenic acid
  • vitamins. B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol, p-aminobenzoic acid and a pharmaceutically acceptable carrier.
  • the present invention is directed to a composition
  • a composition comprising an effective amount of a vitamin B, a C-group composition and an effective amount of a medicament for the treatment and/or prevention of gastrointestinal disorders.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, Vitamin C and an effective amount of a drug for treating and/or preventing gastrointestinal diseases.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid, biotin, vitamin C, Hydrocholine tartrate, inositol, and an effective amount of a medicament for treating and/or preventing gastrointestinal diseases.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, vitamins. B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol, p-aminobenzoic acid, and an effective amount of a medicament for treating and/or preventing gastrointestinal diseases.
  • the present invention is directed to a composition
  • a composition comprising an effective amount of a vitamin B, a Group C composition, and other effective amount of a vitamin family compound.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, Vitamin C and other effective amounts of vitamin compounds.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid, Biotin, vitamin C, choline hydrogen tartrate, inositol, and other effective amounts of vitamin compounds.
  • the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, vitamins. B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol, p-aminobenzoic acid and other effective amounts of vitamin compounds.
  • the other vitamin compounds include vitamin A, vitamin D, vitamin E, vitamin K, and the like.
  • Promoting gastrointestinal motility is used in a method of treating a gastrointestinal dysfunction caused by a drug (for example, an opioid such as morphine-induced intestinal dysfunction or constipation) in a subject in need thereof, the method comprising administering a treatment An effective amount of a vitamin B, C group composition.
  • a drug for example, an opioid such as morphine-induced intestinal dysfunction or constipation
  • the subject may be using opioid or opioid for postoperative pain management or chronic pain management.
  • opioids and opioids include morphine, codeine, oxycodone, hydrocodone, methadone, fentanyl, and anti-inflammatory agents such as acetaminophen or A combination of aspirin).
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, A composition of vitamin C.
  • the multivitamin BC composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid , a combination of biotin, vitamin C, hydrogen choline tartrate, inositol.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, A composition of vitamin B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol and p-aminobenzoic acid.
  • Promoting gastrointestinal motility can be used to treat gastroparesis in a subject in need thereof by administering a therapeutically effective amount of a vitamin B, C-group composition.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, A composition of vitamin C.
  • the multivitamin BC composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid , a combination of biotin, vitamin C, hydrogen choline tartrate, inositol.
  • the complex The vitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, vitamin B12, folic acid, biotin, vitamin C. , a composition of choline hydrogen tartrate, inositol and p-aminobenzoic acid.
  • the method of promoting gastrointestinal motility is used in a method of treating gastroesophageal reflux disease (GERD) in a subject in need thereof, the method comprising administering a therapeutically effective amount of vitamin B, Group C composition.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, A composition of vitamin C.
  • the multivitamin BC composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid , a combination of biotin, vitamin C, hydrogen choline tartrate, inositol.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, A composition of vitamin B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol and p-aminobenzoic acid.
  • the gastroesophageal reflux disease is nocturnal gastroesophageal reflux disease.
  • the invention also provides a method of promoting gastrointestinal motility to treat irritable bowel syndrome (IBS) in a subject in need thereof by administering a therapeutically effective amount of a vitamin B, C-group composition.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, A composition of vitamin C.
  • the multivitamin BC composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid , a combination of biotin, vitamin C, hydrogen choline tartrate, inositol.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, A composition of vitamin B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol and p-aminobenzoic acid.
  • the irritable bowel syndrome may be constipation-type irritable bowel syndrome or constipation/diarrhea alternating irritable bowel syndrome.
  • the invention also provides a method of promoting gastrointestinal motility to treat constipation in a subject in need thereof by administering a therapeutically effective amount of a vitamin B, C-group composition.
  • the constipation includes functional (bad habits, eating habits, senile and other constipation without organic causes) and drug-induced constipation.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, A composition of vitamin C.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, vitamins. B12, a composition of folic acid, biotin, vitamin C, hydrogencholine tartrate, inositol.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, A composition of folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol and p-aminobenzoic acid.
  • the method of promoting gastrointestinal motility is used in the treatment of a gastrointestinal dysfunction caused by surgery or related to gastrointestinal dysfunction (eg, post-operative bowel movement slowing) in a subject in need thereof, the method comprising administering the therapeutically effective Amount of vitamin B, Group C composition.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, A composition of vitamin C.
  • the multivitamin BC composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid , a combination of biotin, vitamin C, hydrogen choline tartrate, inositol.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, A composition of vitamin B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol and p-aminobenzoic acid.
  • a preferred multivitamin BC group composition is a composition comprising vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, vitamin C. .
  • a more preferred multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, folic acid, biotin, vitamin C. , a composition of choline hydrogen tartrate, inositol.
  • the multivitamin BC group composition comprises vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, A composition of vitamin B12, folic acid, biotin, vitamin C, choline hydrogen tartrate, inositol and p-aminobenzoic acid.
  • the dosage form of the multivitamin BC group composition of the present invention may be a chewable tablet, but is not limited thereto, and the composition of the present invention may also be added with various conventional excipients required for preparing different dosage forms, such as a disintegrating agent, a lubricant, and a sticking agent.
  • a pharmaceutical carrier such as a mixture, an antioxidant, a complexing agent or the like can be prepared into any of the commonly used oral dosage forms, such as dispersible tablets, granules, capsules, oral liquids, and the like, by a conventional preparation method.
  • the multivitamin BC group composition of the present invention has various weight ratios of the components, and each of them has a corresponding promoting effect on the gastrointestinal system kinetics.
  • it may comprise the following components by weight: 5-10 parts of vitamin B1, 10-15 parts of vitamin B2, 6-25 parts of vitamin B3, 10-110 parts of vitamin B5, 5-10 parts Vitamin B6, 0.01-0.1 part biotin, 50-500 parts vitamin C.
  • the vitamin B group composition comprises the following components by weight: 10 parts of vitamin B1, 15 parts of vitamin B2, 25 parts of vitamin B3, 110 parts of vitamin B5, 10 parts of vitamin B6 and 0.1 part of biotin. And 150 parts of vitamin C.
  • the vitamin B group composition comprises the following components by weight: 10 parts of vitamin B1, 15 parts of vitamin B2, 25 parts of vitamin B3, 110 parts of vitamin B5, 10 parts of vitamin B6, 0.1 parts Biotin, 0.4 parts folic acid, 250 parts of choline hydrogen tartrate, 250 parts of inositol and 150 parts of vitamin C.
  • the vitamin B group composition comprises the following components by weight: 10 parts of vitamin B1, 15 parts of vitamin B2, 25 parts of vitamin B3, 110 parts of vitamin B5, 10 parts of vitamin B6, 0.1 parts Biotin, 0.4 parts folic acid, 250 parts of choline hydrogen tartrate, 0.025 parts of vitamin B12 and 150 parts of vitamin C.
  • the vitamin B group composition comprises the following components by weight: 10 parts of vitamin B1, 15 parts of vitamin B2, 25 parts of vitamin B3, 110 parts of vitamin B5, 10 parts of vitamin B6, 0.1 Biotin, 0.4 parts folic acid, 250 parts of choline hydrogen tartrate, 250 parts of inositol, 0.025 parts of vitamin B12, 50 parts of p-aminobenzoic acid and 150 parts of vitamin C.
  • part especially when referring to a given amount, refers to an amount within 10% of the positive or negative deviation.
  • vitamin B group composition includes all vitamin B compounds or analogs or derivatives thereof, such as vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid) and vitamin B6.
  • analog refers to any two or more molecules or fragments thereof that are substantially identical in structure and have the same biological activity but may have varying degrees of activity.
  • derivative refers to a more complex compound derived from a hydrogen atom or a group of atoms in a compound which is substituted by another atom or group of atoms.
  • Figure 7 Schematic diagram of the test method for the effect of different multivitamin BC prescriptions on small intestinal propulsion rate in mice treated with loperamide
  • Figure 8 Schematic diagram of the test method for the effect of different multivitamin BC prescriptions on bowel function in mice treated with loperamide
  • This study aimed to evaluate the therapeutic effects of different prescriptions of multivitamin BC tablets by loperamide-induced mouse constipation model.
  • the experimental animals were randomly divided into 8 groups, 10 to 12 in each group.
  • the specific groupings and dosages of BC tablets were shown in Table 1 and Table 2.
  • 1% Tween-80 saline accurately measure 40 ml of normal saline into a 50 ml centrifuge tube, measure 400 ⁇ l Tween-80 with a pipette, add to a centrifuge tube, vortex and mix, and set aside at room temperature. .
  • Composite VB (5X) group According to the equivalent dose of the mouse in Table 2 (*5), weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, biotin and vitamin B12, and added 0.5% CMC. -Na 20ml, shake and mix, A stable suspension is formed. Now available.
  • Composite VB + choline (5X) group According to the equivalent dose of the mouse in Table 2 (*5), weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, biotin, vitamin B12 and heavy tartaric acid. Choline was added to 0.5% CMC-Na 20 ml and vortexed to form a stable suspension. Now available.
  • Composite VB+VC (5X) group According to the equivalent dose of the mouse in Table 2 (*5), weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, biotin, vitamin B12 and vitamin C. Add 20 ml of 0.5% CMC-Na and mix by shaking to form a stable suspension. Now available.
  • Composite VB+VC+Biotin (5X) group According to the equivalent dose (2) of the mouse in Table 2, weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, vitamin B12, vitamin C and 3 parts of biotin (ie 0.3 mg biotin per 100 mg tablet), added with 0.5% CMC-Na 20 ml, and shaken to form a stable suspension. Now available.
  • Compound VB+VC+ choline (5X) group According to the equivalent dose of the mouse in Table 2 (*5), weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, biotin, vitamin B12, Vitamin C and choline bitartrate were added to 20 ml of 0.5% CMC-Na and vortexed to form a stable suspension. Now available.
  • Itopride hydrochloride group 2 tablets of itopride hydrochloride were taken, and after grinding, 0.5 ml of CMC-Na 13 ml was added, and the mixture was shaken to form a stable suspension. Now available.
  • Loperamide Accurately weigh 5.0 mg of loperamide, add 20 ml of physiological saline solution containing 1.0% Tween 80, shake and mix for at least 5 min, and use it now.
  • mice were given free access to drinking water. Each group was administered at a dose of 20 ml/kg.
  • the model group and the normal group were intragastrically administered with 0.5% CMC-Na solution. After 30 minutes of administration, the normal group was subcutaneously.
  • a physiological saline solution containing 1.0% Tween 80 was injected, and the other groups were subcutaneously injected with loperamide solution in an injection volume of 10 ml/kg. After subcutaneous injection for 30 minutes, the ink was administered orally with a dose of 10 ml/kg.
  • the animals were sacrificed by cervical dislocation. Immediately open the abdominal cavity to separate the mesentery. The upper end of the intestine from the pylorus and the lower end to the ileocecal area was cut and placed on the tray. Be careful not to involve the small intestine and gently put the small intestine into a straight line. , measuring the total length of the small intestine Degree, from the pylorus to the ink front, the ink advancement length, calculate the intestinal ink propulsion rate (%).
  • test data were expressed by Mean ⁇ SE, SPSS software was used for one-way analysis of variance, and the comparison between groups was performed by LSD test.
  • This study aimed to evaluate the therapeutic effects of different prescriptions of multivitamin BC tablets by loperamide-induced mouse constipation model.
  • the experimental animals were randomly divided into 8 groups, 5 in each group.
  • the specific groupings and dosages of BC tablets were shown in Table 4 and Table 5.
  • 1% Tween-80 saline accurately measure 40 ml of normal saline into a 50 ml centrifuge tube, measure 400 ⁇ l Tween-80 with a pipette, add to a centrifuge tube, vortex and mix, and set aside at room temperature. .
  • Composite VB (5X) group According to the equivalent dose of the mouse in Table 5 (*5), weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, biotin and vitamin B12, and added 0.5% CMC. -Na 20 ml, vortex and mix to form a stable suspension. Now available.
  • Composite VB + choline (5X) group According to the equivalent dose of the mouse in Table 5 (*5), weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, biotin, vitamin B12 and heavy tartaric acid. Choline was added to 0.5% CMC-Na 20 ml and vortexed to form a stable suspension. Now available.
  • Composite VB+VC (5X) group According to the equivalent dose of the mouse in Table 5 (*5), weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, biotin, vitamin B12 and vitamin C. Add 20 ml of 0.5% CMC-Na and mix by shaking to form a stable suspension. Now available.
  • Composite VB+VC+Biotin (5X) group According to the equivalent dose of mice in Table 5 (*5), weighed vitamin B1, vitamin B2, vitamin B3, vitamin B6, calcium pantothenate, folic acid, vitamin B12, vitamin C and 3 parts of biotin (ie 0.3 mg biotin per 100 mg tablet), added with 0.5% CMC-Na 20 ml, and shaken to form a stable suspension. Now available.
  • Loperamide Accurately weigh 5.0 mg of loperamide, add 20 ml of physiological saline solution containing 1.0% Tween 80, shake and mix for at least 5 min, and use it now.
  • mice were given free access to drinking water. Each group was administered at a dose of 20 ml/kg.
  • the model group and the normal group were intragastrically administered with 0.5% CMC-Na solution. After 30 minutes of administration, the normal group was subcutaneously.
  • a physiological saline solution containing 1.0% Tween 80 was injected, and the other groups were subcutaneously injected with loperamide solution in an injection volume of 10 ml/kg. After 30 minutes of subcutaneous injection, the ink was administered by intragastric administration at a dose of 10 ml/kg [1, 2, 3] .
  • the mice were housed in a single cage, fasted with water, and the body weight of each mouse before and at the end of the experiment was recorded.
  • mice were housed in a single cage, fasted with water, and the body weight of each mouse before and at the end of the experiment was recorded.
  • test data were expressed by Mean ⁇ SE, SPSS software was used for one-way analysis of variance, and the comparison between groups was performed by LSD test.
  • the test results showed that compared with the normal group, the first group of black stool time in the model group was prolonged (264.2 ⁇ 131.18VS104.0 ⁇ 12.00); compared with the model group, the composite VB (5X) group, composite VB+VC (5X) Both the group and the composite VB+VC+choline (5X) group can reduce the first black stool time (264.2 ⁇ 131.18VS 177.2 ⁇ 105.25, 178.8 ⁇ 113.19, 171.4 ⁇ 123.03).
  • the composite VB (5X) group, the composite VB+ choline (5X) group and the composite VB+VC+ organism The number of defecations in the prime (5X) group was higher than that in the model group (2.8 ⁇ 1.92 vs 6.6 ⁇ 3.44, 4.8 ⁇ 2.86, 4.8 ⁇ 2.86); the composite VB (5X) group, the composite VB+choline (5X) group, and the composite VB+VC+
  • the fecal wetness of the biotin (5X) group and the composite VB+VC+choline (5X) group was significantly greater than that of the model group (0.043 ⁇ 0.031 vs 0.092 ⁇ 0.040, 0.068 ⁇ 0.048, 0.059 ⁇ 0.042, 0.054 ⁇ 0.023); composite VB (5X) Group, composite VB+choline (5X) group, composite VB+VC+ bio
  • composite VB (5X) group, composite VB+VC (5X) group, composite VB+VC+ biotin (5X) group and composite VB+VC+choline (5X) group fecal water content Slightly higher than the model group (31.59 ⁇ 25.82 vs 37.19 ⁇ 8.94, 36.56 ⁇ 25.03, 50.95 ⁇ 10.53, 38.31 ⁇ 18.37).
  • Different prescriptions of multivitamin BC tablets can improve bowel function in mice with constipation caused by 2.5mg/kg loperamide.

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Abstract

一种复合物维生素B、C族组合物以及其在制备治疗和/或预防与胃肠系统动力匮乏相关的胃肠状态或疾病的药物或保健食品中的用途，所述组合物包含维生素B族组合物或其类似物或衍生物和维生素C或其类似物或衍生物。

Description

促进胃肠系统动力的复合维生素组合物 技术领域
本发明涉及一种维生素B、C组合物，尤其是一种促进胃肠系统动力的复合维生素B、C组合物。该组合物适用于预防和/或治疗与胃肠动力匮乏相关的状态或疾病。
背景技术
现在，人们生活压力普遍加大，生活节奏加快，竞争日益激烈，胃肠道疾患或胃肠不适者越来越多，其起因是多方面的，其症状也各有不同。
胃肠(gastrointestinal,GI)动力是经由消化系统输送营养物之协调的神经肌肉进程。可参与胃食管反流病、胃轻瘫(例如，糖尿病性和手术后的胃轻瘫)、肠易激综合征(IBS)、肠梗阻和便秘(例如，功能性或药物引起的便秘)之胃肠系统动力削弱是工业化国家最大的医疗保健负担之一。鉴于上述情况，有效促进胃肠系统动力是亟需的并且将成为本领域中的进展。
功能性消化不良(functional dyspepsia)及慢性胃炎常有腹部饱胀感、上腹痛、恶心、食欲减退等症状，胃肠道动力障碍引起胃排空延缓是这类症状发生的一个重要原因。而且胃肠道动力障碍易导致IBS。现治疗胃肠动力的药物有甲氧氯普胺、多潘立酮和伊托必利。
以往治疗胃肠疾病的药物很多，但疗效好且无副作用者甚少，尤其是即可作长期保健作用，又很好改善胃肠道功能促进胃肠动力及减缓胃肠不适症状的药物或保健品更是少之又少。
如之前所述的(1)甲氧氯普胺，该药为多巴胺受体阻断药，具有强大的中枢性镇吐和胃肠道兴奋作用。该药可抑制胃平滑肌松弛，使胃肠平滑肌对胆碱能的反应增加，胃排空加快，增加胃窦部时相活性。此外，该药尚有刺激催乳激素释放的作用。甲氧氯普胺的副作用较常见昏睡、烦躁不安、倦怠无力，另该药大剂量或长期应用可能因阻断多巴胺受体，表现为帕金森综合症的症状。(2)多潘立酮是外周性多巴胺受体拮抗剂，可促进上胃肠道的蠕动和张力恢复正常，促进胃排空，增加胃窦和十二指肠肠运动，协调幽门的收缩，同时也能增强食道的蠕动和食道下端括约肌的张力。由于它对血脑屏障的渗透力差，对脑内多巴胺受体几乎无拮抗作用，国外有静脉大剂量注射引起癫痫发作的报道(国内无此制剂)，但该药是一种强有力的催乳激素释放药，可能导致月经失调。(3)伊托必利具多巴胺受体阻滞和乙酰胆碱酯酶抑制的双重作用，通过刺激内源性乙酰胆碱释放并抑制其水解而增强胃与十二指肠运动，促进胃排空，并具有中度镇吐作用。老年或高龄患者慎用此药。
维生素B都是水溶性维生素，多数是辅酶，参与体内糖、蛋白质和脂肪的代谢。
维维生素B1(硫胺素)能促进肠胃蠕动，增加食欲。维生素B1可抑制胆碱酯酶对乙酰胆碱的水解作用。B1缺乏时，该酶活性增高，加速乙酰胆碱的水解。乙酰胆碱是传递神经冲动的重要物质，它缺乏时，可使神经传导障碍，尤其影响支配胃肠道、腺体等处的神经传导，造成胃肠蠕动缓慢、腹胀、消化腺分泌减少，使食欲减低。
维生素B2是体内黄素酶类辅基的组成部分。可转化为黄素单核苷酸(FMN)和黄素腺嘌呤二核苷酸(FAD)，均为组织呼吸的重要辅酶，在酶系统中起递氢的作用，参与糖、蛋白质、脂肪代谢，并能维持正常视觉功能。另外维生素B2可激活维生素B6，使色氨酸转换为烟酸，可能与维持红细胞的完整性有关。它能维持和改善上皮组织，如消化道黏膜组织的健康。当人体缺少B2，尤其是严重缺乏时，人体腔道的粘膜层就会出现问题，引起粘膜病变，增强化学致癌物的致癌作用。因此维生素B2可防治癌症。
维生素B3(烟酸)在体内构成脱氢酶的辅酶，是B族维生素中人体需要量最多者，它不但是维持消化系统健康的维生素，也能减轻胃肠障碍。烟酸在人体内转化为烟酰胺，烟酰胺是辅酶Ⅰ和辅酶Ⅱ的组成部分，参与体内脂质代谢，组织呼吸的氧化过程和糖类无氧分解的过程。可促进消化系统的健康，减轻胃肠障碍，有效减轻便秘症状。若其缺乏时，可引起口角炎、舌炎、腹泻等，腹泻是本病的典型症状，早期多患便秘，其后因肠壁、消化腺体、肠壁及黏膜、绒毛的萎缩和肠炎的发生常有腹泻，大便呈水样或糊状，量多而有恶臭，也可带血，如病变接近肛门可出现里急后重。腹泻往往严重和难治，可合并吸收障碍。
维生素B5(泛酸)的活性形式是辅酶A，在体内是酰基载体，参与糖、脂肪、蛋白质的代谢。它们是协同作用，调节新陈代谢，维持皮肤和肌肉的健康，增进免疫系统和神经系统的功能，促进细胞生长和分裂(包括促进红血球的产生，预防贫血发生)。缺乏维生素B5的症状有食欲不振、消化不良，易患十二指肠溃疡。
维生素B6包括吡哆醇、吡哆醛和吡哆胺3种，可互相转化。在体内与ATP经酶作用转变成有生理活性的多种酶的辅酶，从而参与氨基酸及脂肪的多种代谢功能。与维生素B1合用，有较强的止痛作用，维生素B12可增强两者联用的止痛效果，缓解因外周神经疾病和脊髓疾病所致的疼痛。有研究报道维生素B6与阿奇霉素混合静滴可减轻阿奇霉素对胃肠道副作用。主要作用在人体的血液、肌肉、神经、皮肤等。功能有抗体的合成、消化系统中胃酸的制造、脂肪与蛋白质利用(尤其在减肥时应补充)、维持钠/钾平衡(稳定神经系统)。维生素B6缺乏损害细胞并影响体液免疫功能，给予维生素B6可提高免疫力，减少体内致癌物，有一定的防癌作用。
维生素B7，又称维生素H、生物素、辅酶R，参与体内的脂肪酸和碳水化合物的代谢；促进蛋白质的合成；还参与维生素B12、叶酸、泛酸的代谢；促进尿素合成与排泄。增强机体的免疫反应和感染的抵抗力，稳定正常组织的溶酶体膜，维持机体的体液免疫、细胞免疫并影响一系列细胞因子的分泌，提高人体免疫功能。减轻肛周湿疹和瘙痒的症状。生物素侧链羧基可通过酰胺键与酶的赖氨酸残基相连。生物素是羧基载体，还参与维生素B12、叶酸、泛酸的代谢。
维生素B9(叶酸)，由蝶啶、对氨基苯甲酸及谷氨酸残基组成的水溶性B族维生素。本药由肠道吸收后，经门静脉进人肝脏，在肝内二氢叶酸还原酶的作用下，转变为具有活性的四氢叶酸。四氢叶酸是体内转移“一碳基团”的载体。“一碳基团”可以连接在四氢叶酸5位或10位碳原子上，主要参与嘌呤核苷酸和嘧啶核苷酸的合成与转化。尿嘧啶核苷酸转化为胸 腺嘧啶核苷酸时所需的甲基即来自携有“一碳基团”的四氢叶酸所提供的甲烯基。因此，叶酸缺乏可致“一碳基团”转移障碍，胸腺嘧啶核苷酸合成困难，DNA合成受到影响，从而使细胞分裂速度减慢，仅停留在G1期，而S期及G2期相对延长。上述改变不仅会影响造血细胞(引起巨幼细胞性贫血)，也会累及体细胞(尤其是消化道黏膜细胞)。叶酸缺乏可导致B1吸收障碍。叶酸对于女性的健康好处广受医学界注意，除了怀孕与哺乳期的妇女应该补充，能够用于预防直肠癌和心脏病。它也被发现能阻止自由基对染色体破坏，人类如缺乏叶酸可引起巨红细胞性贫血以及白细胞减少症。
脱氧腺苷钴胺素是维生素B12在体内主要存在形式，是一种含钴的红色化合物，需转化为甲基钴胺和辅酶B12后才具有活性。维生素B12与叶酸在DNA合成方面发挥着重要的作用。此外维生素B12在红细胞的成熟和神经系统正常维持方面也发挥着重要作用。它和叶酸的作用常互相关联。叶酸在细胞中有多种辅脢形式，有研究提示叶酸对胃肠道癌的发生有干预作用，叶酸可治疗萎缩性胃炎、改善胃粘膜病理。
酒石酸氢胆碱有促使磷脂转变、加速脂肪的运转及利胆作用；肌醇可促进细胞新陈代谢、助长发育、增进食欲。对氨基苯甲酸(PABA)实际上是叶酸的一种成分，在体内它的作用是辅酶，它与叶酸一道工作以促进蛋白质的代谢和血细胞的生成。
维生素C又称抗坏血酸，是抗氧化维生素当中的一种，它参与体内羟化反应，为形成骨骼、牙齿、结缔组织及非上皮组织细胞间粘物所必需，可维持牙齿、骨骼、血管的正常功能，增加对疾病的抵抗能力。据有关资料报道维生素C在各人群中有不同程度的缺乏。当身体出现一些小毛病时，就应该及时补充适量的维生素和矿物质来改善营养缺乏症，尤其是中老年应较为重视。维生素对许多疾病都有预防作用，而许多疾病的发生可能或多或少与维生素C的缺乏有关系，另外维生素C还能和许多其他药物联合用药治疗某些疾病。维生素C是一种抗氧化剂，保护身体免于自由基的威胁，维生素C同时也是一种辅酶。许多研究证明维生素C可以阻断致癌物N～亚硝基化合物合成，防止盐腌、渍和熏制食品含亚硝酸盐(咸肉、香肠之类也一样)中致癌物亚硝酸铵的形成，预防癌症，特别是对直肠癌和结肠癌有较好的预防作用。同时具有软化肛肠血管、增加肛肠弹性的作用。VC容易被热或氧化剂破坏，特别是光、微量重金属和荧光物质等更能促进其氧化，这使得VC在应用上受到了很大地限制。因此，维生素C的衍生物，包括VC的金属盐类、VC与各种酸形成的酯类及VC与糖类的化合物等，既能克服VC不稳定的缺点，又能更好地发挥VC的生理功能。这些衍生物包括维生素C(L-抗坏血酸)、维生素C钠(L-抗坏血酸钠)、维生素C磷酸酯镁、维生素C多磷酸酯、维生素C棕榈酸酯、维生素C硬脂酸酯、维生素C葡萄糖化合物等。
从作用机制上看，维生素B族是参与人体能量代谢的重要辅酶，而维生素C可以促进人体对维生素B族成员的吸收。复合维生素B、C通过增强人体的能量代谢，为胃肠提供更多的能量来改善胃肠动力不足所引起的功能性消化不良。这种能量代谢的增强包括协助碳水化合物和脂肪释放能量、分解氨基酸及输送含有营养素的氧及能量到整个机体。复合维生素BC将有可能成为一种新的具有较高安全性的促进胃肠系统动力的药物或保健食品，然而到目前 为止还没有事实证据证明维生素B、C对胃肠系统动力的促进作用，特别是在病理状态下，维生素B、C对胃肠系统动力紊乱的治疗和调节作用。另外由于维生素B家族成员众多，并且存在相互依赖的关系，因此维生素B的成分选择和配伍，对于制备治疗或调节胃肠系统动力紊乱的药物或保健食品至关重要。
发明内容
A.发明概述
本发明涉及在有此需要之对象中促进胃肠系统动力的方法，其中所述对象患有胃肠系统疾病(即，失调症、病症、症状或者药物或手术引起的功能障碍)。该方法包括向有此需要之对象施用治疗有效量的维生素B和维生素C族组合物。本发明中所指的维生素包括其相应的类似物或衍生物，如维生素B1是指硫胺素或其类似物或衍生物；维生素B2是指核黄素或其类似物或衍生物；维生素B3是指烟酸或其类似物或衍生物；维生素B5是指泛酸或其类似物或衍生物；维生素B6是指吡哆醇或其类似物或衍生物；维生素B7是生物素或其类似物或衍生物；维生素B9是指叶酸或其类似物或衍生物；维生素B12是指氰钴胺或其类似物或衍生物；维生素C是指抗坏血酸或其类似物或衍生物；等等。在一个优选实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中，维生素B族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
另一方面，本发明提供了一种组合物，该组合物包括有效量的维生素B族、维生素C族组合物以及药学上可接受的载体。在一个优选的实施方案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C以及药学上可接受的载体。在一个更优选的实施方案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、、维生素C、酒石酸氢胆碱、肌醇以及药学上可接受的载体。在另一个更优选的实施方案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇、对氨基苯甲酸以及药学上可接受的载体。
另一方面，本发明涉及一种组合物，该组合物包括有效量的维生素B、C族组合物以及有效量的治疗和/或预防胃肠疾病的药物。在一个优选的实施方案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C以及有效量的治疗和/或预防胃肠疾病的药物。在一个更优选的实施方 案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇以及有效量的治疗和/或预防胃肠疾病的药物。在另一个更优选的实施方案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇、对氨基苯甲酸以及有效量的治疗和/或预防胃肠疾病的药物。
另一方面，本发明涉及一种组合物，该组合物包括有效量的维生素B、C族组合物以及其他有效量的维生素族化合物。在一个优选的实施方案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C以及其他有效量的维生素族化合物。在一个更优选的实施方案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇以及其他有效量的维生素族化合物。在另一个更优选的实施方案中，该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇、对氨基苯甲酸以及其他有效量的维生素族化合物。所述其他维生素族化合物包括维生素A、维生素D、维生素E、维生素K等。
促进胃肠动力被用于在有此需要之对象中治疗由药物引起的胃肠功能障碍(例如，阿片类药物，如吗啡引起之肠道功能障碍或便秘)的方法中，该方法包括施用治疗有效量的维生素B、C族组合物。所述对象可正在使用阿片物质或阿片类物质进行手术后疼痛控制或慢性疼痛控制。阿片物质和阿片类物质的实例包括吗啡、可待因、羟考酮、氢可酮(hydrocodone)、美沙酮(methadone)、芬太尼(fentanyl)以及其与抗炎剂(例如对乙酰氨基酚或阿司匹林)的组合。在一个优选实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
促进胃肠动力可用于在有此需要之对象中治疗胃轻瘫，其通过施用治疗有效量的维生素B、C族组合物。在一个优选实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中，复 合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
在另一实施方案中，促进胃肠动力被用于在有此需要之对象中治疗胃食管反流病(gastro esophageal reflux disease,GERD)之方法中，该方法包括施用治疗有效量的维生素B、C族组合物。在一个优选实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。在一个具体实施方案中，所述胃食管反流病为夜间胃食管反流病。
本发明还提供了在有此需要之对象中促进胃肠动力以治疗肠易激综合征(irritable bowel syndrome,IBS)的方法，其通过施用治疗有效量的维生素B、C族组合物来实现。在一个优选实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。所述肠易激综合征可为便秘型肠易激综合征或便秘/腹泻交替型肠易激综合征。
本发明还提供了在有此需要之对象中促进胃肠动力以治疗便秘的方法，其通过施用治疗有效量的维生素B、C族组合物来实现。所述便秘包括功能性(不良生活习惯、饮食习惯，老年性等无器质性病因的便秘)和药物引起的便秘。在一个优选实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
在一个实施方案中，促进胃肠动力被用于在有此需要之对象中治疗由手术引起或相关的胃肠功能障碍(例如手术后肠蠕动减慢)的方法中，该方法包括施用治疗有效量的维生素B、 C族组合物。在一个优选实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
优选的复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。更优选的复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中，复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
本发明的复合维生素BC族组合物的剂型可以为口嚼片，但不限于此，本发明组合物还可加入制备不同剂型时所需的各种常规辅料，如崩解剂、润滑剂、粘合剂、抗氧剂、络合剂等药用载体，以常规的制剂方法制成任何一种常用的口服剂型，如分散片、颗粒剂、胶囊剂、口服液等其他剂型。
本发明的复合维生素BC族组合物，其各组份的重量配比可有多种选择，其均对胃肠系统动力有相应的促进作用。在某些实施方案中，其可包含如下重量配比的组份：5-10份维生素B1，10-15份维生素B2，6-25份维生素B3，10-110份维生素B5，5-10份维生素B6，0.01-0.1份生物素，50-500份维生素C。在一个优选实施方案中，维生素B族组合物包含如下重量配比的组份：10份维生素B1，15份维生素B2，25份维生素B3，110份维生素B5，10份维生素B6和0.1份生物素和150份维生素C。在一个更优选的实施方案中，维生素B族组合物包含如下重量配比的组份：10份维生素B1，15份维生素B2，25份维生素B3，110份维生素B5，10份维生素B6，0.1份生物素，0.4份叶酸，250份酒石酸氢胆碱，250份肌醇和150份维生素C。在一个更优选的实施方案中，维生素B族组合物包含如下重量配比的组份：10份维生素B1，15份维生素B2，25份维生素B3，110份维生素B5，10份维生素B6，0.1份生物素，0.4份叶酸，250份酒石酸氢胆碱，0.025份维生素B12和150份维生素C。在另一个更优选的实施方案中，维生素B族组合物包含如下重量配比的组份：10份维生素B1，15份维生素B2，25份维生素B3，110份维生素B5，10份维生素B6，0.1份生物素，0.4份叶酸，250份酒石酸氢胆碱，250份肌醇，0.025份维生素B12，50份对氨基苯甲酸和150份维生素C。
B.定义
除另有定义，这里使用的所有科技术语与本发明所属技术领域的普通技术人员理解含义相同。所有专利文献、专利申请文献、公开的专利文献和其它出版物均作为参考。如本节阐述的定义与上述参考文献所述的定义不一致或相反时，以本节阐述的定义为准。
除非在上下文中明确表明，在此所用“一个”的意思是“至少一个”或“一个或多于一个”。
术语“份”，特别是涉及一个给定的量，是指正负偏差在10％以内的量。
此处所使用的术语“包含(comprises)”、“包含(comprising)”、“包括(includes)”、“包括(including)”、“含有(contains)”、“含有(containing)”及其任何变体旨在涵盖非独占性的包含物，例如包含、包括或含有一种元素或一列表的元素的过程、方法、加工产品或物质的组合物不仅包括那些元素还可能包括没有明确地列出的或该过程、方法、加工产品或物质的组合物的固有的其它元素。
此处所用的术语“维生素B族组合物”包括所有的维生素B化合物或其类似物或衍生物，如维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)和维生素B6等。
此处所用的术语“类似物”是指结构大致相同、并具有相同生物活性但可以有不同程度活性的任何两个以上分子或者是其中片段。所用术语“衍生物”是指化合物中的氢原子或原子团被其他原子或原子团取代而衍生的较复杂的化合物。
附图说明
图1：给药后墨汁在小鼠小肠内推进率(％)的变化
图2：给药后小鼠排首粒黑便时间
图3：给药后小鼠6h内排便粒数
图4：给药后小鼠6h内排便湿重
图5：给药后小鼠6h内排便干重
图6：给药后小鼠6h内排便含水量
图7：不同复合维生素BC处方对洛哌丁胺致便秘小鼠小肠推进率影响的试验方法示意图
图8：不同复合维生素BC处方对洛哌丁胺致便秘小鼠排便功能影响的试验方法示意图
具体实施方式
实施例1不同复合维生素BC处方对洛哌丁胺致便秘小鼠小肠推进率的影响
1.研究目的
本研究旨在通过洛哌丁胺诱导的小鼠便秘模型评价复合维生素BC片不同处方的治疗效果。
2.试验材料
2.1试剂与仪器
Figure PCTCN2017109280-appb-000001
2.2实验动物
种属：小鼠
品系：C57BL/6
性别和数量：雄性，80只
动物周龄：6-8周
体重范围：17.0-20.0g
动物来源：上海灵畅生物科技有限公司
动物合格证号：2013001820135
3.试验设计与方法
3.1.试验分组
实验动物采用随机数表法，随机分为8组，每组10～12只，BC片不同处方具体分组及给药剂量见表1和表2。
表1.各组小鼠给药计量表
Figure PCTCN2017109280-appb-000002
Figure PCTCN2017109280-appb-000003
表2.复合维生素BC片各成份给药剂量表
Figure PCTCN2017109280-appb-000004
3.2试剂配制
1)0.5％CMC-Na溶液：称取CMC-Na粉末2.0g，缓慢加入300ml超纯水，磁力搅拌至完全溶解，定容到400ml，配制成0.5％的澄清溶液，置于4℃备用。
2)1％吐温-80生理盐水：用量筒准确量取40ml生理盐水加入50ml离心管中，用移液器量取400μl吐温-80，加入离心管中，涡旋振荡混匀，室温放置备用。
3)5％墨汁：称取阿拉伯树胶100g，加水800ml，煮沸至溶液透明，称取活性炭粉50g加入上述溶液中煮沸3次，待溶液凉后加水定容到1000ml。
4)复合VB(5X)组：按表2小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、生物素和维生素B12，加入0.5％CMC-Na 20ml，振荡混匀， 形成稳定的混悬液。现配现用。
5)复合VB+胆碱(5X)组：按表2小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、生物素、维生素B12和重酒石酸胆碱，加入0.5％CMC-Na20ml，振荡混匀，形成稳定的混悬液。现配现用。
6)复合VB+VC(5X)组：按表2小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、生物素、维生素B12和维生素C，加入0.5％CMC-Na 20ml，振荡混匀，形成稳定的混悬液。现配现用。
7)复合VB+VC+生物素(5X)组：按表2小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、维生素B12、维生素C和3份生物素(即每100mg片剂中含0.3mg生物素)，加入0.5％CMC-Na 20ml，振荡混匀，形成稳定的混悬液。现配现用。
8)复合VB+VC+胆碱(5X)组：按表2小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、生物素、维生素B12、维生素C和重酒石酸胆碱，加入0.5％CMC-Na 20ml，振荡混匀，形成稳定的混悬液。现配现用。
9)盐酸伊托必利组：取盐酸伊托必利2片，研磨后加入0.5％CMC-Na 13ml，振荡混匀，形成稳定的混悬液。现配现用。
10)洛哌丁胺：精确称取5.0mg洛哌丁胺，加入20ml含1.0％Tween 80的生理盐水溶液，振荡混匀后超声至少5min，现配现用。
3.3试验方法
小鼠自由进食饮水，各组按照给药剂量给药，给药体积为20ml/kg，模型组和正常组按同样剂量灌胃给予0.5％CMC-Na溶液；给药30分钟后，正常组皮下注射含1.0％Tween 80的生理盐水溶液，其他组皮下注射洛哌丁胺溶液，注射体积为10ml/kg。皮下注射30分钟后，灌胃给予墨汁，给药体积为10ml/kg。
3.4观察指标
小肠墨汁推进率(％)＝(墨汁推进长度/小肠总长度)×100
灌胃给予墨汁20分钟后，脱颈椎处死动物，立即打开腹腔分离肠系膜，剪取上端自幽门、下端至回盲部的肠管，置于托盘上，小心不能牵扯小肠，轻轻将小肠摆成直线，测量小肠总长 度，从幽门至墨汁前沿为墨汁推进长度，计算小肠墨汁推进率(％)。
3.5数据分析
试验数据均用Mean±SE表示，采用SPSS软件进行单因素方差分析，组间比较采用LSD检验。
4.试验结果
不同处方的维生素BC片对墨汁在小鼠小肠内推进距离和推进率(％)影响见表3和图1。
表3.复合维生素BC片不同处方对洛哌丁胺致便秘小鼠小肠推进率的影响(Mean±SD)
Figure PCTCN2017109280-appb-000005
与模型组相比较，*P<0.05,**P<0.01,***P<0.001
试验结果显示：与正常组相比，模型组的小肠推进率(％)显著降低(64.5±8.5VS 28.1±5.3)，表明小鼠便秘模型制备成功；与模型组相比，伊托必利阳性药对照组、复合VB(5X)组、复合VB+胆碱(5X)组、复合VB+VC(5X)组、复合VB+VC+生物素(5X)组和复合VB+VC+胆碱(5X)组均能不同程度改善小鼠小肠推进率(％)(28.1±5.3VS 42.7±5.5、42.7±12.4、45.2±8.0、43.0±8.2、40.1±6.5、52.1±6.8)。
5.结论
不同处方的复合维生素BC片均能显著改善2.5mg/kg洛哌丁胺致便秘小鼠小肠推进率，其中复合VB+胆碱(5X)组、复合VB+VC(5X)组和复合VB+VC+胆碱(5X)组效果优于阳性药对照组。
实施例2 不同复合维生素BC处方对洛哌丁胺致便秘小鼠排便功能的影响
1.研究目的
本研究旨在通过洛哌丁胺诱导的小鼠便秘模型评价复合维生素BC片不同处方的治疗效果。
2.试验材料
2.1试剂与仪器
Figure PCTCN2017109280-appb-000006
2.2实验动物
种属：小鼠
品系：C57BL/6
性别和数量：雄性，40只
动物周龄：6-8周
体重范围：22.0-27.0g
动物来源：上海灵畅生物科技有限公司
动物合格证号：2013001820476
3.试验设计与方法
3.1.试验分组
实验动物采用随机数表法，随机分为8组，每组5只，BC片不同处方具体分组及给药剂量见表4和表5。
表4.各组小鼠给药计量表
Figure PCTCN2017109280-appb-000007
Figure PCTCN2017109280-appb-000008
表5.复合维生素BC片各成份给药剂量表
Figure PCTCN2017109280-appb-000009
3.2试剂配制
2)0.5％CMC-Na溶液：称取CMC-Na粉末2.0g，缓慢加入300ml超纯水，磁力搅拌至完全溶解，定容到400ml，配制成0.5％的澄清溶液，置于4℃备用。
6)1％吐温-80生理盐水：用量筒准确量取40ml生理盐水加入50ml离心管中，用移液器量取400μl吐温-80，加入离心管中，涡旋振荡混匀，室温放置备用。
7)5％墨汁：称取阿拉伯树胶100g，加水800ml，煮沸至溶液透明，称取活性炭粉50g加入 上述溶液中煮沸3次，待溶液凉后加水定容到1000ml。
8)复合VB(5X)组：按表5小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、生物素和维生素B12，加入0.5％CMC-Na 20ml，振荡混匀，形成稳定的混悬液。现配现用。
9)复合VB+胆碱(5X)组：按表5小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、生物素、维生素B12和重酒石酸胆碱，加入0.5％CMC-Na20ml，振荡混匀，形成稳定的混悬液。现配现用。
6)复合VB+VC(5X)组：按表5小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、生物素、维生素B12和维生素C，加入0.5％CMC-Na 20ml，振荡混匀，形成稳定的混悬液。现配现用。
7)复合VB+VC+生物素(5X)组：按表5小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、维生素B12、维生素C和3份生物素(即每100mg片剂中含0.3mg生物素)，加入0.5％CMC-Na 20ml，振荡混匀，形成稳定的混悬液。现配现用。
8)复合VB+VC+胆碱(5X)组：按表5小鼠等效剂量(*5)称取维生素B1、维生素B2、维生素B3、维生素B6、泛酸钙、叶酸、生物素、维生素B12、维生素C和重酒石酸胆碱，加入0.5％CMC-Na 20ml，振荡混匀，形成稳定的混悬液。现配现用。
9)洛哌丁胺：精确称取5.0mg洛哌丁胺，加入20ml含1.0％Tween 80的生理盐水溶液，振荡混匀后超声至少5min，现配现用。
3.3试验方法
小鼠自由进食饮水，各组按照给药剂量给药，给药体积为20ml/kg，模型组和正常组按同样剂量灌胃给予0.5％CMC-Na溶液；给药30分钟后，正常组皮下注射含1.0％Tween 80的生理盐水溶液，其他组皮下注射洛哌丁胺溶液，注射体积为10ml/kg。皮下注射30min后，灌胃给予墨汁，给药体积为10ml/kg[1,2,3]。灌墨后15min开始计时，分别记录排首粒黑便的时间、0-2h，4-6h的排便粒数，称重并测定粪便的干重(60℃，6h)，然后计算粪便含水量(％)[(湿 便质量-干便质量)/湿便质量*100％]。实验期间小鼠均单笼饲养，禁食不禁水，并且记录每只小鼠给药前及实验结束时的体重。
3.4观察指标
灌墨后15min开始计时，分别记录排首粒黑便的时间、0-2h、2-4h、4-6h的排便粒数，称重并测定粪便的干重(60℃，6h)，然后计算粪便含水量(％)[(湿便质量-干便质量)/湿便质量*100％]。实验期间小鼠均单笼饲养，禁食不禁水，并且记录每只小鼠给药前及实验结束时的体重。
3.5数据分析
试验数据均用Mean±SE表示，采用SPSS软件进行单因素方差分析，组间比较采用LSD检验。
4.试验结果
不同处方的维生素BC片对对小鼠排首粒黑便时间及6h内排便数量的影响见表6和图2、图3。
不同处方的维生素BC片对对小鼠6h内排便湿重、干重及粪便含水量的影响见表7和图4、图5和图6。
表6.复合维生素BC片不同处方对洛哌丁胺致便秘小鼠排首粒黑便时间及6h内排便粒数的影响(Mean±SE)
表7.复合维生素BC片不同处方对洛哌丁胺致便秘小鼠6h内排便湿重、干重及粪便含水量的影响(Mean±SE)
Figure PCTCN2017109280-appb-000011
试验结果显示：与正常组相比，模型组的排首粒黑便时间延长(264.2±131.18VS104.0±12.00)；与模型组相比，复合VB(5X)组、复合VB+VC(5X)组和复合VB+VC+胆碱(5X)组均能一定程度减少排首例黑便时间(264.2±131.18VS 177.2±105.25、178.8±113.19、171.4±123.03)。
与正常组相比，模型组6h内排便粒数、粪便湿重、干重均减少，排便含水量轻微下调；复合VB(5X)组、复合VB+胆碱(5X)组和复合VB+VC+生物素(5X)组排便粒数多于模型组(2.8±1.92 vs 6.6±3.44、4.8±2.86、4.8±2.86)；复合VB(5X)组、复合VB+胆碱(5X)组、复合VB+VC+生物素(5X)组和复合VB+VC+胆碱(5X)组粪便湿重大于模型组(0.043±0.031 vs 0.092±0.040、0.068±0.048、0.059±0.042、0.054±0.023)；复合VB(5X)组、复合VB+胆碱(5X)组、复合VB+VC+生物素(5X)组和复合VB+VC+胆碱(5X)组粪便干重大于模型组(0.0246±0.019 vs 0.0567±0.023、0.046±0.031、0.026±0.014、0.032±0.015)；复合VB(5X)组、复合VB+VC(5X)组、复合VB+VC+生物素(5X)组和复合VB+VC+胆碱(5X)组粪便含水量略高于模型组(31.59±25.82 vs 37.19±8.94、36.56±25.03、50.95±10.53、38.31±18.37)。
5.结论
不同处方的复合维生素BC片均能改善2.5mg/kg洛哌丁胺致便秘小鼠排便功能。
为了更清楚地描述和理解本发明，我们通过举例的方式详细描述了本发明，但显而易见的是，本技术领域中普通技术人员可以在不背离权利要求的精神和范围的前提下，对本发明做出适当的改变或修改。

Claims (10)

  1. 一种复合维生素B、C族组合物，其可用于预防和/或治疗与胃肠系统动力匮乏相关的状态或疾病。
  2. 根据权利要求1所述的组合物，其中所述复合维生素B、C组合物包括维生素B族组合物或其类似物或衍生物和维生素C或其类似物或衍生物。
  3. 根据权利要求1或2所述的组合物，其中所述复合维生素B、C族组合物还包括酒石酸氢胆碱。
  4. 根据权利要求1或2所述的组合物，其中所述复合维生素BC族组合物还包括肌醇或对氨基苯甲酸。
  5. 根据权利要求2所述的组合物，其特征在于其包含如下重量配比的组份：100份维生素B1，100份维生素B2，100份维生素B3，100份维生素B6，109份泛酸钙，0.4份叶酸，0.1份维生素B12，0.1份生物素和150份维生素C。
  6. 根据权利要求2所述的组合物，其特征在于其包含如下重量配比的组份：100份维生素B1，100份维生素B2，100份维生素B3，100份维生素B6，109份泛酸钙，0.4份叶酸，0.1份维生素B12，0.3份生物素和150份维生素C。
  7. 根据权利要求3所述的组合物，其特征在于其包含如下重量配比的组份：100份维生素B1，100份维生素B2，100份维生素B3，100份维生素B6，109份泛酸钙，0.4份叶酸，0.1份维生素B12，0.1份生物和250份酒石酸氢胆碱。
  8. 根据权利要求3所述的组合物，其特征在于其包含如下重量配比的组份：100份维生素B1，100份维生素B2，100份维生素B3，100份维生素B6，109份泛酸钙，0.4份叶酸，0.1份维生素B12，0.1份生物素，250份酒石酸氢胆碱和150份维生素C。
  9. 一种复合维生素B、C族组合物在制备治疗和/或预防与胃肠系统动力匮乏相关的胃肠状态或疾病的药物或保健食品中的用途。
  10. 根据权利要求9所述的用途，其中所述复合维生素BC组合物包括维生素B族组合物或其类似物或衍生物和维生素C或其类似物或衍生物。
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006108208A1 (en) * 2004-10-14 2006-10-19 Adventures Plus Pty Ltd A method for the treatment of gastrointestinal and other disorders with an admixture of vitamins and minerals
CN104337813A (zh) * 2013-07-23 2015-02-11 上海泽生科技开发有限公司 使用维生素b组合物促进胃肠系统动力的方法
CN104856048A (zh) * 2015-06-18 2015-08-26 安徽医联大成医药科技有限公司 一种促进肠胃蠕动的食品配方及其制备方法
CN106265696A (zh) * 2015-06-12 2017-01-04 上海泽生科技开发有限公司 使用复合维生素b、c组合物促进胃肠系统动力的方法

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5626884A (en) * 1995-08-18 1997-05-06 Lockett; Curtis G. Treatment of sickle cell disease
WO1999064022A1 (en) * 1998-06-10 1999-12-16 Crum Albert B Prophylactic and therapeutic nutritional supplement for creation/maintenance of health-protective intestinal microflora and enhancement of the immune system
AU2003218319A1 (en) * 2002-03-22 2003-10-13 Doc's Guide, Inc. Multivitamin and mineral nutritional supplement
WO2011121150A1 (es) 2010-03-31 2011-10-06 Vegenat, S.A. Producto alimenticio enteral u oral especialmente destinado para la nutrición, prevención y mejora de alteraciones neurológicas, neurodegenerativas o trastornos cognitivos
WO2011143587A1 (en) 2010-05-13 2011-11-17 Nitromega Corp. Nitro fatty acids - neuroprotection and/or inhibition of cognitive decline
CN103327986B (zh) 2010-07-22 2018-05-25 雷文制药有限公司 包含使用磁偶极子稳定化溶液的治疗或改善疾病并增强表现的方法
WO2013066151A1 (en) 2011-10-31 2013-05-10 N.V. Nutricia Improving recognition
WO2013129931A1 (en) 2012-03-02 2013-09-06 N.V. Nutricia Method for improving functional synaptic connectivity
CN104256652A (zh) 2014-10-08 2015-01-07 李明刚 一种口服复合维生素纳米脂质体
CN104306405B (zh) * 2014-10-28 2018-04-06 朱洞风 提高肛肠免疫力预防便秘和肛肠疾病的保健栓剂及其制备方法和应用
CN104922164B (zh) 2014-12-12 2020-06-02 中国医科大学 一种治疗阿尔茨海默病的药物复合制剂
CN108079008A (zh) * 2016-11-23 2018-05-29 上海泽生科技开发股份有限公司 促进胃肠系统动力的复合维生素组合物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006108208A1 (en) * 2004-10-14 2006-10-19 Adventures Plus Pty Ltd A method for the treatment of gastrointestinal and other disorders with an admixture of vitamins and minerals
CN104337813A (zh) * 2013-07-23 2015-02-11 上海泽生科技开发有限公司 使用维生素b组合物促进胃肠系统动力的方法
CN106265696A (zh) * 2015-06-12 2017-01-04 上海泽生科技开发有限公司 使用复合维生素b、c组合物促进胃肠系统动力的方法
CN104856048A (zh) * 2015-06-18 2015-08-26 安徽医联大成医药科技有限公司 一种促进肠胃蠕动的食品配方及其制备方法

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