CN107648307B - Composition, preparation method and application thereof - Google Patents

Composition, preparation method and application thereof Download PDF

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CN107648307B
CN107648307B CN201710895567.3A CN201710895567A CN107648307B CN 107648307 B CN107648307 B CN 107648307B CN 201710895567 A CN201710895567 A CN 201710895567A CN 107648307 B CN107648307 B CN 107648307B
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刘晔峰
曹翠峰
刘勇
翁慧燕
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Yangshengtang Pharmaceutical Co ltd
Zhejiang Yangshengtang Institute of Natural Medication Co Ltd
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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
    • A61K31/01—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

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Abstract

The invention belongs to the field of medicines or foods, and particularly relates to a composition which comprises 0.3-280 parts by weight of lycopene and 0.2-140 parts by weight of rosemary extract; also relates to a preparation method and application of the composition. The composition can treat/assist to treat/prevent/improve frequent nocturia symptoms caused by diabetes insipidus, primary aldosteronism, hypercalcemia or prostatic hyperplasia, and has the treatment/assist to treat/prevent/improve prostatic hyperplasia or prostatic cancer.

Description

Composition, preparation method and application thereof
Technical Field
The invention belongs to the field of medicines or foods, and particularly relates to a composition, a preparation method of the composition and a medicine or food application of the composition.
Background
Diabetes Insipidus (DI) is a group of clinical syndromes in which Arginine Vasopressin (AVP), also called antidiuretic hormone (ADH), is deficient to varying degrees due to hypothalamic-neurohypophyseal lesions or deficiency in sensitivity of the kidney to AVP is caused by various lesions, making the kidney unable to concentrate the raw urine and excrete large amounts of hypo-osmotic urine, the former being Central Diabetes Insipidus (CDI) and the latter being renal diabetes insipidus (NDI). The clinical characteristics of diabetes insipidus are polydipsia, frequent urination and hypotonic urination, which can occur at any age, the proportion of male and female is 2:1 in young and strong years, the disease is slow to occur, and the disease condition is gradually obvious within a few days.
Primary Aldosteronism (PA) is a group of diseases characterized by increased aldosterone secretion and inhibited renin-angiotensin system but not regulated by sodium load, is secondary hypertension caused by increased aldosterone secretion, and is currently considered to account for 4.3% of patients with primary hypertension, 9.5% of patients with referral hypertension and 20% of patients with refractory hypertension, and is the most common cause of secondary hypertension. The disease has the symptoms of frequent urination clinically.
Hypercalcemia (HC) refers to an abnormally elevated concentration of ionic calcium in the serum. HC occurs when the calcium (gut, bone) entering the extracellular fluid exceeds the calcium (gut, kidney) being excreted. HC is one of the more common endocrine and metabolic disorders in clinic, and serious patients can have high calcium crisis, and if the patients are not diagnosed and treated in time, the life can be threatened. The incidence of HC in the general population reaches 1%, and the incidence of HC in hospitalized patients reaches 3%. HC can cause renal tubular damage, kidney concentration function decline, polydipsia, frequent urination and dehydration; renal calculus and renal calcification may also occur.
Benign Prostatic Hyperplasia (BPH) is a common disease causing micturition disorders in middle-aged and elderly men, with an increasing incidence of disease with increasing age, typically occurring initially after age 40, with a incidence of greater than 50% in the 60-year-old population and up to 83% in the 80-year-old population. Moderate to severe lower urinary tract symptoms occur in about 50% of the male population that is histologically diagnosed with BPH. There are studies that show asians are more likely to develop moderate to severe BPH-related symptoms than americans.
Prostate cancer is one of the common malignancies of the male reproductive system, and the incidence of prostate cancer is the first in europe and america, especially in the united states. At present, although the incidence of prostate cancer in China is far lower than that in western countries, in recent years, with the change of life styles of people, the prolonging of life and the improvement of medical care and diagnosis levels, the incidence of prostate cancer is gradually increased by Chinese data statistics. The prostate cancer has the characteristics of slow development and hidden onset, can be asymptomatic in the early stage, and the prostate cancer detected by pathological sections in the operation of prostate hyperplasia accounts for about 5 percent.
There is a need for a medicament for treating or preventing frequent nocturia caused by diabetes insipidus, primary aldosteronism, hypercalcemia or prostatic hyperplasia, and for treating or preventing prostatic hyperplasia or prostate cancer.
Lycopene is mainly distributed in the testes and adrenal glands of the human body, and is also more distributed in the liver, adipose tissues, prostate and ovaries. About 50% of the carotenoids in human body are lycopene, and the carotenoid concentration of normal prostate tissue is 2 times higher than that of benign prostatic hyperplasia tissue and 5-8 times higher than that of prostate cancer tissue. At present, the research on carotenoids associated with prostatic hyperplasia is mostly focused on lycopene. Kim HS et al (Nutr Cancer,2003,47(1):40-47) firstly found that, by supplementing tomato juice containing 30mg of lycopene every day, apoptotic cells in BPH tissues increased significantly after three weeks, and the number of apoptotic cells died increased and Bax gene expression decreased. Herzog A et al (FASEB J,2005,19(2):272-274) showed that lycopene attenuated androgen signaling pathway conduction in prostate tissue, down-regulated insulin-like growth factor-1 (IGF-1) expression, and helped to prevent BPH.
Rosemary, known as Oenothera odorata, Rosmarinus officinalis L.belonging to the family Labiatae. Rosemary has been widely used in the fields of food and food processing as a natural antioxidant with high efficiency and no toxic or side effect, and in addition, rosemary has an obvious inhibitory effect on the growth of escherichia coli, staphylococcus aureus, rhizoctonia solani and other bacteria, and rosemary is also commonly used for treating inflammatory diseases such as arthritis, nephritis and the like in European traditional medical treatment.
Vitamin B2The riboflavin is used as a coenzyme of glutathione reductase and has the function of maintaining the concentration of reduced glutathione in vivo, the riboflavin can be converted into dihydroriboflavin in vivo to directly play an antioxidation role, and the riboflavin is also helpful for maintaining the normal structure and function of intestinal mucosa and promoting the absorption and the transportation of iron.
Zinc is widely distributed in all tissues, organs, body fluids and secretions of human bodies, participates in the synthesis of various enzymes of the human bodies, can control the integrity and stability of cell biological membranes, and the deficiency of zinc can cause mental retardation, immunity reduction, inappetence, hypogonadism and the like.
Vitamin C, also known as ascorbic acid, is a water-soluble vitamin, the reduction of vitamin C can promote the formation of body antibodies, promote the absorption of iron, the formation of tetrahydrofolic acid and maintain the activity of mercaptoenzyme, and the vitamin C also participates in the hydroxylation reaction of the body, can promote the synthesis of collagen and neurotransmitter, promote the hydroxylation of steroid and can promote the hydroxylation and detoxification of organic matters or poisons.
Vitamin E, also known as tocopherol, is a fat-soluble vitamin that is stored mainly in adipose tissue, liver and muscle, with highest concentrations of adrenal gland, pituitary gland, testis, and platelets in various tissues and organs. Vitamin E is an important antioxidant in the non-enzymatic antioxidant system.
Disclosure of Invention
The invention provides a composition which can treat/assist in treating/preventing/improving frequent nocturia symptoms caused by diabetes insipidus, primary aldosteronism, hypercalcemia or prostatic hyperplasia, and has a treatment/assist in treating/preventing/improving effect on prostatic hyperplasia or prostate cancer. On the basis, the invention also provides a medicament and a health food.
The present invention relates in a first aspect to a composition comprising:
lycopene 0.3 to 280 parts by weight (e.g., 0.4 parts by weight, 0.6 parts by weight, 0.8 parts by weight, 1 part by weight, 2 parts by weight, 3 parts by weight, 6 parts by weight, 8 parts by weight, 10 parts by weight, 13 parts by weight, 15 parts by weight, 20 parts by weight, 30 parts by weight, 50 parts by weight, 60 parts by weight, 80 parts by weight, 100 parts by weight, 130 parts by weight, 140 parts by weight, 150 parts by weight, 155 parts by weight, 160 parts by weight, 163 parts by weight, 168 parts by weight, 170 parts by weight, 175 parts by weight, 180 parts by weight, 186 parts by weight, 190 parts by weight, 200 parts by weight, 220 parts by weight, 240 parts by weight, 260 parts by weight, 270 parts by weight)
0.2 to 140 parts by weight of rosemary extract (for example, 0.5 parts by weight, 0.6 parts by weight, 0.8 parts by weight, 1 part by weight, 2 parts by weight, 3 parts by weight, 4 parts by weight, 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 14 parts by weight, 18 parts by weight, 20 parts by weight, 30 parts by weight, 40 parts by weight, 60 parts by weight, 70 parts by weight, 75 parts by weight, 80 parts by weight, 85 parts by weight, 88 parts by weight, 90 parts by weight, 93 parts by weight, 95 parts by weight, 97 parts by weight, 98 parts by weight, 99 parts by weight, 100 parts by weight, 120 parts by weight, 130 parts by weight).
In one embodiment of the first aspect of the present invention, the composition comprises:
0.6-260 parts by weight of lycopene
0.5-120 parts of rosemary extract.
In one embodiment of the first aspect of the present invention, the lycopene is provided in the form of a lycopene oleoresin, lycopene powder/crystals/granules; preferably, the lycopene content in the lycopene oleoresin or lycopene powder/crystals/granules is 1% to 99.9%, more preferably 3%, 5%, 6%, 10%, 30%, 40%, 50%, 70%, 80%, 90%, 95%, 98%, 99%.
In one embodiment of the first aspect of the present invention, the composition further comprises vitamin ABiotin B2And/or salts thereof.
In one embodiment of the first aspect of the present invention, the vitamin B2And/or a salt thereof is 1 to 160 parts by weight, for example, 2 parts by weight, 3 parts by weight, 4 parts by weight, 5 parts by weight, 6 parts by weight, 7 parts by weight, 9 parts by weight, 10 parts by weight, 12 parts by weight, 15 parts by weight, 18 parts by weight, 20 parts by weight, 30 parts by weight, 38 parts by weight, 40 parts by weight, 42 parts by weight, 45 parts by weight, 47 parts by weight, 49 parts by weight, 50 parts by weight, 51 parts by weight, 55 parts by weight, 60 parts by weight, 70 parts by weight, 80 parts by weight, 84 parts by weight, 88 parts by weight, 90 parts by weight, 93 parts by weight, 97 parts by weight, 100 parts by weight, 106 parts by weight, 110 parts by weight, 115 parts by weight, 117 parts by weight, 120 parts by weight, 130 parts by weight, 140 parts by weight, 150 parts by weight.
In one embodiment of the first aspect of the present invention, the vitamin B2And/or 1 to 140 parts by weight of a salt thereof.
In one embodiment of the first aspect of the present invention, the composition further comprises at least one selected from the group consisting of vitamin C, a vitamin C salt, a pharmaceutically or dietetically acceptable zinc-containing compound, biological zinc, vitamin E and tocotrienols.
In one embodiment of the first aspect of the invention, the composition further comprises vitamin C and/or a salt thereof, a pharmaceutically or dietetically acceptable zinc-containing compound and/or biological zinc, and vitamin E and/or tocotrienol.
In one embodiment of the first aspect of the invention, the composition further comprises vitamin C, vitamin E, and a pharmaceutically or food acceptable zinc-containing compound and/or biological zinc.
In one embodiment of the first aspect of the invention, one or more of the following 1) to 5) is included:
1) the vitamin C and/or a salt thereof is 0.5 to 2200 parts by weight, preferably 1 to 2100 parts by weight, for example, 2 parts by weight, 4 parts by weight, 5 parts by weight, 8 parts by weight, 10 parts by weight, 13 parts by weight, 16 parts by weight, 18 parts by weight, 20 parts by weight, 21 parts by weight, 23 parts by weight, 25 parts by weight, 27 parts by weight, 30 parts by weight, 33 parts by weight, 40 parts by weight, 50 parts by weight, 60 parts by weight, 70 parts by weight, 80 parts by weight, 90 parts by weight, 100 parts by weight, 110 parts by weight, 120 parts by weight, 130 parts by weight, 140 parts by weight, 148 parts by weight, 150 parts by weight, 153 parts by weight, 155 parts by weight, 160 parts by weight, 180 parts by weight, 200 parts by weight, 240 parts by weight, 300 parts by weight, 360 parts by weight, 380 parts by weight, 400 parts by weight, 420 parts by weight, 500 parts by weight, 700 parts by weight, 1000 parts by weight, 1300 parts by weight, 1600 parts by weight, 1800 parts by weight, 1900 parts by weight, 2000 parts by weight, 2100 parts by weight, 2200 parts by weight;
2) 1 to 840 parts by weight, preferably 2 to 790 parts by weight, such as 3 parts by weight, 5 parts by weight, 7 parts by weight, 10 parts by weight, 15 parts by weight, 23 parts by weight, 30 parts by weight, 50 parts by weight, 100 parts by weight, 130 parts by weight, 160 parts by weight, 180 parts by weight, 200 parts by weight, 210 parts by weight, 230 parts by weight, 250 parts by weight, 270 parts by weight, 300 parts by weight, 400 parts by weight, 500 parts by weight, 550 parts by weight, 570 parts by weight, 600 parts by weight, 620 parts by weight, 630 parts by weight, 660 parts by weight, 670 parts by weight, 680 parts by weight, 700 parts by weight, 750 parts by weight, 800 parts by weight, 830 parts by weight;
3) 4 to 150 parts by weight, preferably 7 to 130 parts by weight, for example 5 parts by weight, 6 parts by weight, 7 parts by weight, 9 parts by weight, 10 parts by weight, 12 parts by weight, 14 parts by weight, 16 parts by weight, 20 parts by weight, 30 parts by weight, 40 parts by weight, 41 parts by weight, 43 parts by weight, 45 parts by weight, 47 parts by weight, 50 parts by weight, 52 parts by weight, 54 parts by weight, 56 parts by weight, 60 parts by weight, 70 parts by weight, 80 parts by weight, 90 parts by weight, 100 parts by weight, 104 parts by weight, 107 parts by weight, 110 parts by weight, 113 parts by weight, 116 parts by weight, 118 parts by weight, 120 parts by weight, 125 parts by weight, 130 parts by weight, 140 parts by weight, 142 parts by weight, 147 parts by weight, 150 parts by weight;
4) the pharmaceutically or food acceptable zinc-containing compound is at least one selected from zinc sulfate, zinc carbonate, zinc lactate, zinc oxide, zinc gluconate, zinc citrate, zinc glycinate, zinc acetate, zinc chloride and hydrates thereof;
5) the biological zinc is yeast zinc.
In the invention, the salt is a food acceptable salt or a pharmaceutically acceptable salt.
In one embodiment of the present invention, the salts include, but are not limited to, hydrochloride, sulfate, nitrate, phosphate, hydroiodide, formate, citrate, acetate, trichloroacetate, trifluoroacetate, benzoate, fumarate, maleate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, 2-dichloroacetate, acylated amino acid, adipate, alginate, ascorbate, L-aspartate, 4-acetamidobenzoate, (+) -camphorsulfonate, (+) - (1S) -camphorsulfonate, decanoate, hexanoate, octanoate, cinnamate, cyclamate, lauryl sulfate, ethane-1, 2-disulfonate, ethanesulfonate, 2-hydroxyethanesulfonate, galactaric acid, galactose, acetate, trichloro acetate, trifluoroacetate, benzoate, fumarate, and mixtures thereof, Gentisate, glucoheptonate, D-gluconate, D-glucuronate, L-glutamate, alpha-oxo-glutarate, glycolate, hippurate, (+) -L-lactate, (+ -) -DL-lactate, lactobionate, (-) -L-malate, malonate, (+ -) -DL-mandelate, methanesulfonate, naphthalene-2-sulfonate, naphthalene-1, 5-disulfonate, 1-hydroxy-2-naphthoate, nicotinate, oleate, orotate, oxalate, palmitate, pamoate, embonate, L-pyroglutamate, salicylate, 4-amino-salicylate, sebacate, stearate, succinate, tartrate, maleate, fumarate, maleate, salicylate, and any combination thereof, Tannate, (+) -L-tartrate, thiocyanate, undecylenate.
In one embodiment of the first aspect of the invention, the rosemary extract is a water-soluble or fat-soluble extract, preferably a fat-soluble extract.
In one embodiment of the first aspect of the present invention, the rosemary extract is an extract obtained by extracting stems and leaves of rosemary (Rosmarinus officinalis L.) with a solvent or by supercritical carbon dioxide extraction and refining. The extraction solvent is at least one selected from water, methanol, ethanol, acetone and n-hexane.
In one embodiment of the first aspect of the invention, the rosemary extract meets the requirements of GB1886.172-2016, "national food safety standard food additive rosemary extract".
In one embodiment of the first aspect of the invention, the rosemary extract is a powder or a liquid.
In one embodiment of the first aspect of the present invention, the physicochemical indices of rosemary extract are shown in the following table:
Figure BDA0001422082490000071
ais meant for water soluble powder products only;
brepresents a product in which only n-hexane or methanol is used as an extraction solvent;
1shows the test according to the method in appendix A of GB1886.172-2016 "national food safety Standard food additive rosemary extract";
2indicating the detection according to GB 5009.3 distillation method or Karl Fischer method;
3indicating detection according to the method of GB 5009.75 or GB 5009.12;
4indicating detection according to the method of GB 5009.76.
In one embodiment of the first aspect of the invention, vitamin B2The salt is riboflavin-5' -sodium phosphate.
In one embodiment of the first aspect of the present invention, the ascorbic acid salt is selected from at least one of ascorbic acid-6-palmitate, calcium ascorbate, sodium ascorbate and potassium ascorbate.
In one embodiment of the first aspect of the invention, the vitamin E is selected from the group consisting of natural d-type alpha tocopherol, natural d-type beta tocopherol, natural d-type gamma tocopherol, natural d-type delta tocopherol, natural d-type alpha tocopherol acetate, natural d-type beta tocopherol acetate, natural d-type gamma tocopherol acetate, natural d-type delta tocopherol acetate, natural d-type alpha tocopherol succinate, natural d-type beta tocopherol succinate, natural d-type gamma tocopherol succinate, natural d-type delta tocopherol succinate, mixed tocopherol, synthetic dl-type alpha tocopherol, synthetic dl-type beta tocopherol, synthetic dl-type gamma tocopherol, synthetic dl-type alpha tocopherol acetate, synthetic dl-type beta tocopherol acetate, synthetic dl-type gamma tocopherol acetate, synthetic dl-type delta tocopherol acetate, synthetic dl-type alpha tocopherol succinate, synthetic dl-type tocopherol, At least one of dl-type gamma tocopherol succinate and dl-type delta tocopherol succinate is synthesized.
In one embodiment of the first aspect of the present invention, the tocotrienol is selected from at least one of natural d-type alpha tocotrienol, natural d-type beta tocotrienol, natural d-type gamma tocotrienol, natural d-type delta tocotrienol, natural d-type alpha tocotrienol acetate, natural d-type beta tocotrienol acetate, natural d-type gamma tocotrienol acetate, natural d-type delta tocotrienol acetate, natural d-type alpha tocotrienol succinate, natural d-type beta tocotrienol succinate, natural d-type gamma tocotrienol succinate, and natural d-type delta tocotrienol succinate.
In one embodiment of the first aspect of the present invention, the composition further comprises an adjuvant; preferably, the adjuvant is selected from at least one of diluents, stabilizers, antioxidants, preservatives, binders, glidants, flavors, colorants, wetting agents, anticaking agents, fillers, disintegrants and carriers.
In the invention, the auxiliary material is an auxiliary material acceptable in food or an auxiliary material acceptable in pharmacy.
A second aspect of the invention relates to a medicament or food product comprising a composition according to any one of the first aspects of the invention.
In one embodiment of the second aspect of the invention, the food product is a health food product.
In one embodiment of the second aspect of the present invention, the pharmaceutical or food is in the form of a capsule (e.g., soft or hard), solid granules or tablets, preferably a capsule; more preferably, the composition is the contents of a capsule.
A third aspect of the present invention relates to a process for preparing the composition of any one of the first aspects of the present invention, which is process 1, process 2 or process 3; wherein,
the method 1 comprises the following steps:
(1) extracting herba Rosmarini officinalis with vitamin B2Vitamin B2Mixing salt, vitamin C salt, at least one of pharmaceutically or food acceptable zinc-containing compound and biological zinc, and diluent to obtain mixture;
(2) mixing the mixture obtained in step (1), lycopene, at least one selected from diluent, stabilizer and antioxidant, and optionally vitamin E and/or tocotrienol;
the method 2 comprises the following steps:
(I) extracting rosemary with a vitamin B2Vitamin B2Mixing salt, vitamin C salt, at least one of pharmaceutically or food acceptable zinc-containing compound and biological zinc, and at least one of diluent, filler and disintegrant to obtain mixture;
(II) mixing the mixture obtained in the step (I) with lycopene, and granulating to obtain solid particles;
(III) mixing the solid granules obtained in the step (II) with at least one selected from the group consisting of a disintegrant, a lubricant, a glidant and an anticaking agent;
the method 3 comprises the following steps:
mixing rosemary extract, lycopene and at least one selected from the group consisting of stabilizers, diluents, fillers, glidants, lubricants and anticaking agents.
In one embodiment of the third aspect of the present invention, method 3 further comprises adding vitamin B2Vitamin B2At least one of salt, vitamin C salt, pharmaceutically or food acceptable zinc-containing compound and biological zinc.
Diluents, stabilizers, antioxidants, preservatives, binders, glidants, flavoring agents, colorants, wetting agents, anticaking agents, fillers, disintegrants and carriers used in the present invention are all conventionally used in the art.
In the present invention, the diluent includes, but is not limited to, safflower seed oil, soybean oil, peanut oil, rapeseed oil, corn oil, sea buckthorn oil, linseed oil, perilla seed oil, camellia seed oil, sunflower seed oil, walnut oil, fish oil, and PEG.
In the present invention, stabilizers include, but are not limited to, beeswax, phospholipids, PEG, caprylic acid, capric acid glycerides (MCT oil), candelilla wax, palm wax, and glyceryl mono/distearate.
In the present invention, antioxidants include, but are not limited to, tea polyphenols, vitamin E.
In the present invention, lubricants include, but are not limited to, magnesium stearate.
In the present invention, the anticaking agent includes, but is not limited to, magnesium stearate, silicon dioxide.
In the present invention, glidants include, but are not limited to, silicon dioxide.
In the present invention, the disintegrant includes, but is not limited to, sodium carboxymethyl starch, starch.
In the present invention, fillers include, but are not limited to, sorbitol, lactose, starch, microcrystalline cellulose, and dextrin.
In certain embodiments of the invention, the biological zinc (yeast zinc) is pharmaceutically or food acceptable biological zinc (yeast zinc).
The fourth aspect of the present invention relates to the use of the composition according to any one of the first aspect of the present invention for the preparation of a medicament for the treatment and/or prevention of frequent nocturia symptoms caused by diabetes insipidus, primary aldosteronism, hypercalcemia or prostate hyperplasia, or for the preparation of a medicament for the treatment and/or prevention of prostate hyperplasia or prostate cancer.
A fifth aspect of the present invention relates to the use of the composition according to any one of the first aspect of the present invention for the preparation of a food product for preventing and/or ameliorating frequent nocturia symptoms caused by diabetes insipidus, primary aldosteronism, hypercalcemia or prostate hyperplasia, or for the preparation of a food product for preventing and/or ameliorating prostate hyperplasia or prostate cancer; preferably, the food is a health food.
The following documents are incorporated herein in their entirety:
GB1886.172-2016 "food safety national standard food additive rosemary extract";
GB 14752-2(riboflavin) ";
GB 14754-;
GB 8820-;
GB1886.78-2016 "national food safety Standard food additive lycopene (synthetic)";
GB 1886.233-2016 "national food safety Standard food additive vitamin E";
GB/T22327-;
GB/T11765-;
GB/T8235 + 2008 'linseed oil';
GB/T22465-;
GB/T24314-;
GB 1996.84-2015 "national food safety Standard food additive carnauba wax".
In the present invention, if not otherwise stated:
the term "rosemary extract" refers to rosemary extract as specified in GB1886.172-2016 "national food safety Standard food additive rosemary extract".
The term "lycopene" is one of the carotenoid compounds, a natural plant pigment. Molecular formula C40H56536.88 molecular weight, deep red needle crystal, 172-173 deg.C melting point, dissolving in benzene, chloroform, carbon disulfide, and boiling ether and zeolite oil ether. For example, lycopene as specified in GB1886.78-2016, "national food safety Standard food additive lycopene (synthetic)".
The term "vitamin B2"of the formula C17H20N4O6Molecular weight 376.38, also known as vitamin G or riboflavin, orange yellow crystals, slightly bitter, melting point 280 ℃ (decomposed), is slightly soluble in water and ethanol, and insoluble in ether and chloroform, and exists in meat, liver, egg, milk, vegetables and soybean. For example, GB 14752-2Vitamin B as defined in (Riboflavin)2。
The term "vitamin C", also known as ascorbic acid, is a water-soluble vitamin, the reduction of which can promote the formation of antibodies in the body, promote the absorption of iron, the formation of tetrahydrofolic acid and maintain the activity of mercaptoenzyme, and which also participates in the hydroxylation reaction of the body, can promote the synthesis of collagen and neurotransmitters, promote the hydroxylation of steroids and can promote the hydroxylation detoxification of organic substances or poisons. For example, vitamin C specified in GB 14754-.
The term "vitamin E", also known as tocopherol, is a fat-soluble vitamin that is stored primarily in adipose tissue, liver and muscle, with highest concentrations of adrenal glands, pituitary gland, testes and platelets in various tissues and organs. Vitamin E is an important antioxidant in the non-enzymatic antioxidant system. For example, vitamin E as specified in GB 1886.233-2016, "national food safety Standard food additive vitamin E".
The term "tocotrienol" is an isomer of tocopherol, abundant in palm oil and rice bran oil, with a chemical structure similar to tocopherol, with antioxidant, lipid peroxidation inhibiting, cholesterol synthesis lowering, antitumor and neuroprotective effects.
The term "biological zinc" also called protein zinc, also called zinc protein, zinc binding protein, is a conjugate of protein and zinc, the connection between them can be either in the form of a compound bound by covalent bond or in the form of a chelate mainly with coordination bond.
The term "yeast zinc" refers to that zinc element is added in the process of culturing yeast, and the zinc element is absorbed and transformed in the growth process of yeast, so that the zinc is organically combined with protein and polysaccharide in the yeast body, thereby eliminating the toxic and side reaction and gastrointestinal stimulation of inorganic zinc and organic zinc with chemical properties to human bodies, and enabling the zinc to be more efficiently and safely absorbed and utilized by the human bodies.
The term "lycopene oleoresin" refers to an oily substance obtained by extracting tomato and its products with supercritical carbon dioxide or organic solvent, and evaporating the organic solvent from the extractive solution.
The term "lycopene powder/crystals" refers to a high content of powdery or crystalline lycopene prepared by wittig condensation using tomatoes and products thereof as raw materials or using synthetic intermediates commonly used in the production of other carotenoids of foods as raw materials.
The invention has the following beneficial effects:
the composition can treat/assist to treat/prevent/improve frequent nocturia symptoms caused by diabetes insipidus, primary aldosteronism, hypercalcemia or prostatic hyperplasia, and has good treatment/assist to treat/prevent/improve prostatic hyperplasia or prostatic cancer.
Drawings
In order that the present disclosure may be more readily and clearly understood, reference is now made to the following detailed description of the present disclosure taken in conjunction with the accompanying drawings, in which:
FIG. 1 is a graph showing the average number of urination per day of rats in each group of test example 1.
Detailed Description
The materials and reagents used in the following examples, comparative examples and test examples were as follows:
candelilla wax: purchased from cantonese biotechnology limited, guangzhou;
sunflower seed oil: purchase from the jaboticari group;
oil tea seed oil: purchase from the jaboticari group;
vitamin B2: purchased from tsuki biotechnology limited, zhejiang;
linseed oil: purchased from Shandong Fushikang Biotech Ltd;
purple perilla seed oil: purchased from Jiangxi Yisen botanical flavors, Inc.;
tea polyphenol: purchased from Jiangsu de & Biotech limited;
phospholipid: purchased from jiaji china ltd;
beeswax: purchased from Longxiang beeswax products, Inc., Dongguang county, Shandong;
safflower seed oil: purchased from Zhongliang group, Inc.;
zinc gluconate: purchased from zhengzhou repulpe bioengineering, ltd;
zinc citrate: purchased from zhengzhou repulpe bioengineering, ltd;
zinc lactate: purchased from zhengzhou repulpe bioengineering, ltd;
zinc oxide: purchased from Guangzhou Tuoyi trade company Limited;
vitamin C: purchased from shanghai lexiang biotechnology limited;
vitamin E: purchased from the Disemann group;
carnauba wax: purchased from cantonese biotechnology limited, guangzhou;
fish oil: purchased from jiaji china ltd;
walnut oil: purchased from Shandong Fushikang Biotech Ltd;
lycopene oleoresin containing 2% lycopene: purchased from Xinjiang Keyu science and technology;
lycopene oleoresin containing 5% lycopene: purchased from Xinjiang Keyu science and technology;
lycopene oleoresin containing 10% lycopene: purchased from Xinjiang Keyu science and technology;
lycopene oleoresin containing 50% lycopene: purchased from Xinjiang Keyu science and technology;
lycopene crystals containing 96% lycopene: purchased from le conruid food additives (changzhou) limited;
lycopene particles containing 5% lycopene: purchased from le conruid food additives (changzhou) limited;
rosemary extract: purchased from guangzhou congruence;
rice bran wax: purchased from san bee chemical ltd, guangzhou;
peanut oil: purchased from Shandong mountain Song food science and technology Ltd;
zinc-rich yeast: purchased from Angel Yeast Ltd;
lactose: purchased from Zhengzhou dragon biochemical products, Inc.;
sorbitol: purchased from rogowtt (china) fine chemical limited;
dextrin: purchased from rogowtt (china) fine chemical limited;
starch: purchased from rogowtt (china) fine chemical limited;
magnesium stearate: purchased from Anhui mountain river pharmaceutic adjuvant, Inc.;
silicon dioxide: purchased from Anhui mountain river pharmaceutic adjuvant, Inc.;
sodium carboxymethyl starch: purchased from xu zhou prosperous technologies ltd;
coating powder (opadry): purchased from shanghai carlekang limited.
Example 1
50g of candelilla wax and 200g of sunflower seed oil are put into a mixing tank to be heated to 70 +/-5 ℃, and the temperature is reduced to 50 +/-5 ℃ to be used as a standby solution. Mixing 95g herba Rosmarini officinalis extract and 5g vitamin B2200g of zinc lactate, 2kg of vitamin C, 1.2kg of peanut oil and 1.1kg of camellia seed oil are uniformly stirred and then are uniformly dispersed by a colloid mill to obtain the dispersed material. Adding the dispersed material, 50g of lycopene oleoresin containing 2% lycopene, 10g of vitamin E and the standby solution into a vacuum emulsification tank, emulsifying and shearing uniformly, controlling the vacuum degree to be 0.06 +/-0.02 MPa, stirring for more than 10 minutes, shearing for more than 20 minutes, sieving the obtained feed liquid to be used as content feed liquid, and storing the content feed liquid into a feed liquid barrel for standby.
Adding 1.8kg of water and 900g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 2kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment until the gelatin is completely dissolved, stirring uniformly, vacuum degassing, cooling, sieving, transferring into a gel barrel, keeping the temperature and standing for more than 2 hours.
Putting the content material liquid and the glue solution into a pelleting machine for pelleting, and then carrying out shaping, drying, polishing and packaging to obtain the capsule 1.
Example 2
930g of vitamin B210g of vitamin C, 25g of rosemary extract, 1kg of rapeseed oil and 500g of perilla seed oil are stirred uniformly and then are ground and dispersed uniformly by a ball mill to obtain the dispersed material. Adding the dispersed material, 2.5kg of lycopene crystal containing 96% lycopene, 25g of tea polyphenol and 10g of phospholipid into a vacuum emulsification tank, emulsifying and shearing uniformly, controlling the vacuum degree to be 0.06 +/-0.02 MPa, stirring for more than 10 minutes, shearing for more than 20 minutes, sieving the obtained feed liquid to be used as content feed liquid, and storing the content feed liquid into a feed liquid barrel for later use.
Adding 2kg of water and 500g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 1.6kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment until the gelatin is completely dissolved, stirring uniformly, vacuum degassing, cooling, sieving, transferring into a sol barrel, keeping the temperature and standing for more than 2 hours.
Putting the content material liquid and the glue solution into a pelleting machine for pelleting, and then carrying out shaping, drying, polishing and packaging to obtain the capsule 2.
Example 3
Placing 250g of beeswax and 500g of safflower seed oil in a mixing tank, heating to 65 +/-5 ℃, and cooling to 45 +/-5 ℃ to obtain a standby solution. Mixing 60g of vitamin B2333g of zinc gluconate, 200g of vitamin C, 0.5g of rosemary extract and 1.6kg of safflower seed oil are stirred uniformly and then are ground and dispersed uniformly by a colloid mill to obtain the dispersed material. Adding the dispersed material, 2kg lycopene oleoresin containing 5% lycopene, 56.5g vitamin E and the standby solution into a vacuum emulsifying tank, emulsifying and shearing uniformly, controlling the vacuum degree to be 0.06 + -0.02 MPa, stirring for more than 10 minutes, shearing for more than 40 minutes, sieving the obtained feed liquid to be used as inner materialFeed solution of contents (Composition A) And storing the mixture into a material liquid barrel for later use.
Adding 2kg of water and 800g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 2kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment, stirring uniformly, degassing in vacuum, cooling, sieving, transferring into a gel barrel, keeping the temperature, and standing for more than 2 hours.
Putting the content material liquid and the glue solution into a pelleting machine for pelleting, and then carrying out shaping, drying, polishing and packaging to obtain the capsule 3.
Example 4
100g of carnauba wax and 500g of fish oil are put into a dosing tank to be heated to 80 plus or minus 5 ℃, and the solution is cooled to 60 plus or minus 5 ℃ to be used as a standby solution. 98g of vitamin B250g of vitamin C, 1.5kg of zinc citrate, 2g of rosemary extract and 2kg of walnut oil are stirred uniformly, and then are ground by a colloid mill to be dispersed uniformly, so as to obtain the dispersed material. Adding the dispersed material, 700g of lycopene oleoresin containing 50% lycopene, 50g of glyceryl monostearate and the standby solution into a vacuum emulsification tank, emulsifying and shearing uniformly, controlling the vacuum degree to be 0.06 +/-0.02 MPa, stirring for more than 10 minutes, shearing for more than 20 minutes, sieving the obtained feed liquid to be used as content feed liquid, and storing the content feed liquid into a feed liquid barrel for standby.
Adding 1.8kg of water and 900g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 2kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment until the gelatin is completely dissolved, stirring uniformly, vacuum degassing, cooling, sieving, transferring into a gel barrel, keeping the temperature and standing for more than 2 hours.
Putting the content material liquid and the glue solution into a pelleting machine for pelleting, and then carrying out shaping, drying, polishing and packaging to obtain the capsule 4.
Example 5
Placing 250g of beeswax and 2.75kg of safflower seed oil in a mixing tank, heating to 65 +/-5 ℃, and cooling to 45 +/-5 ℃ to obtain a standby solution. Adding 0.5g herba Rosmarini officinalis extract, 2kg lycopene oleoresin containing 5% lycopene and the solution for use together into vacuumEmulsifying and shearing in an emulsifying tank uniformly, controlling vacuum degree at 0.06 + -0.02 MPa, stirring for more than 10 min, shearing for more than 40 min, sieving the obtained feed liquid to obtain content feed liquid ((Composition B) And storing the mixture into a material liquid barrel for later use.
Adding 2kg of water and 800g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 2kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment after the gelatin is completely dissolved, stirring uniformly, degassing in vacuum, cooling, sieving, transferring into a gelatin liquid barrel, keeping the temperature and standing for more than 2 hours.
Putting the content material liquid and the glue solution into a pelleting machine for pelleting, and then carrying out shaping, drying, polishing and packaging to obtain the capsule 5.
Example 6
Placing 250g of beeswax and 1kg of safflower seed oil in a mixing tank, heating to 65 +/-5 ℃, and cooling to 45 +/-5 ℃ to obtain a standby solution. Mixing 60g of vitamin B20.5g of rosemary extract and 1.69kg of safflower oil are stirred uniformly and then are ground and dispersed uniformly by a colloid mill to obtain the dispersed material. Adding dispersed material, 2kg lycopene oleoresin containing 5% lycopene and standby solution into vacuum emulsifying tank, emulsifying and shearing uniformly, controlling vacuum degree at 0.06 + -0.02 MPa, stirring for more than 10 min, shearing for more than 40 min, sieving the obtained feed liquid to obtain content feed liquid (C)Composition C) And storing the mixture into a material liquid barrel for later use.
Adding 2kg of water and 800g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 2kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment after the gelatin is completely dissolved, stirring uniformly, degassing in vacuum, cooling, sieving, transferring into a gelatin liquid barrel, keeping the temperature and standing for more than 2 hours.
Placing the content material liquid and the glue solution into a pelleting machine for pelleting, and then carrying out shaping, drying, polishing and packaging to obtain the capsule 6.
Example 7
500g of rice bran wax and 800g of soybean oil are placed in a mixing tank to be heated to 80 +/-5 ℃, and the temperature is reduced to 60 +/-5 ℃ to be used as a standby solution. Adding 500g of vitaminB2800g of vitamin C, 5g of rosemary extract, 850g of sea buckthorn oil and 1kg of linseed oil are uniformly stirred and then ground and uniformly dispersed by a ball mill and the like to obtain a dispersed material. Adding the dispersed material, 300g of lycopene oleoresin containing 10% lycopene, 250g of vitamin E and the standby solution into a vacuum emulsification tank, emulsifying and shearing uniformly, controlling the vacuum degree to be 0.06 +/-0.02 MPa, stirring for more than 10 minutes, shearing for more than 40 minutes, sieving the obtained feed liquid to be used as content feed liquid, and storing the content feed liquid into a feed liquid barrel for standby.
Adding 2kg of water and 800g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 2kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment after the gelatin is completely dissolved, stirring uniformly, degassing in vacuum, cooling, sieving, transferring into a gelatin liquid barrel, keeping the temperature and standing for more than 2 hours.
Putting the content material liquid and the glue solution into a pelleting machine for pelleting, and then carrying out shaping, drying, polishing and packaging to obtain the capsule 7.
Example 8
Mixing herba Rosmarini officinalis 10g extract and vitamin B150 g2200g of zinc yeast, 2kg of lycopene granules containing 5% of lycopene, 1.5kg of lactose, 1kg of sorbitol, 50g of magnesium stearate and 50g of silicon dioxide are placed in a mixer to be uniformly mixed, and the uniformly mixed mixture is filled into hard capsules or pressed into tablets to obtain capsules 8 or tablets 1.
Example 9
Mixing 50g herba Rosmarini officinalis extract, 350g vitamin B2100g of vitamin C, 125g of zinc oxide, 500g of starch, 500g of microcrystalline cellulose and 1kg of dextrin are placed in a mixer to be uniformly mixed, 300g of lycopene oleoresin containing 10% of lycopene is added, the mixture is stirred at a high speed for 30 minutes, the materials are transferred to a wet granulation machine to obtain 20-mesh granules, the granules are dried in a vacuum oven at 50 ℃ for 80 minutes to obtain 14-mesh granules, then the 14-mesh granules are mixed with 30g of sodium carboxymethyl starch, 15g of magnesium stearate and 15g of silicon dioxide for 10 minutes, tabletting is carried out, 100g of coating powder is prepared into coating liquid, and the tablets obtained are coated to obtain the tablet 2.
Comparative example 1
The same procedure as in example 5 was repeated except that the addition of rosemary extract was omitted, and a content liquid (Lycopene medicine) And storing the mixture in a feed liquid barrel for later use.
Adding 2kg of water and 800g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 2kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment after the gelatin is completely dissolved, stirring uniformly, degassing in vacuum, cooling, sieving, transferring into a gelatin liquid barrel, keeping the temperature and standing for more than 2 hours.
And putting the content material liquid and the glue solution into a pelleting machine for pelleting, and then shaping, drying, polishing and packaging to obtain the capsule I.
Comparative example 2
Placing 250g of beeswax and 1kg of safflower seed oil in a mixing tank, heating to 65 +/-5 ℃, and cooling to 45 +/-5 ℃ to obtain a standby solution. Mixing 60g of vitamin B2And 1.69kg of safflower oil, and then the materials are uniformly dispersed by a colloid mill to obtain the dispersed materials. Adding dispersed material, 2kg lycopene oleoresin containing 5% lycopene and standby solution into vacuum emulsifying tank, emulsifying and shearing uniformly, controlling vacuum degree at 0.06 + -0.02 MPa, stirring for more than 10 min, shearing for more than 40 min, sieving the obtained feed liquid to obtain content feed liquid (C)Composition I) And storing the mixture into a material liquid barrel for later use.
Adding 2kg of water and 800g of glycerol into a sol tank, heating and stirring, heating to 75 +/-5 ℃, keeping constant temperature, adding 2kg of gelatin, stirring, keeping the temperature, adding uniformly dispersed pigment after the gelatin is completely dissolved, stirring uniformly, degassing in vacuum, cooling, sieving, transferring into a gelatin liquid barrel, keeping the temperature and standing for more than 2 hours.
And putting the content material liquid and the glue solution into a pelleting machine for pelleting, and then shaping, drying, polishing and packaging to obtain the capsule II.
Test example 1: study of the number of urination and influence of prostate tissue on drugs in rats
1. Experimental drugs:
composition a in example 3;
composition B in example 5;
composition C in example 6;
the lycopene drug of comparative example 1;
composition i in comparative example 2.
2. The experimental method comprises the following steps:
SD male rats of 3-4 months age are randomly divided into a normal group, a model group, a composition A group, a composition B group, a composition C group, a lycopene group and a composition I group, and each group comprises 6 animals. Pentobarbital sodium 40mg/kg is anesthetized by intraperitoneal injection, sterile surgery is performed on scrotum, bilateral testes are removed from other groups except a normal group, and the postoperative recovery lasts for 1 week. Except for normal groups injected with physiological saline subcutaneously, other groups injected with testosterone propionate 5mg/kg subcutaneously every day for 28 days to establish a rat Benign Prostatic Hyperplasia (BPH) model. Meanwhile, the corresponding medicines are given according to experimental groups every day, each group adopts intragastric administration, the intragastric volume is 0.1mL/10g body weight, and the administration is carried out once a day for 28 consecutive days. Rats were fed in metabolism cages and were fed with free water. The number of urination times between 9:00pm and 12:00pm per day was monitored and recorded by computer-connected metabolic cages, and averaged over 28 days, as shown in figure 1. After 28 days, the weight was taken, the prostate tissue was rapidly harvested after anesthesia, the prostate wet weight was taken, and the prostate index was calculated according to the following formula, the results of which are shown in fig. 1 and table 1.
Prostate index ═ prostate wet weight (mg)/rat body weight (g)
TABLE 1
Figure BDA0001422082490000201
a: the model group has very significant difference compared with the normal group, and p is less than 0.01;
b: compared with a model group, the model group has very significant difference, and p is less than 0.01;
#: compared with a model group, the model group has obvious difference, and p is less than 0.05;
c: compared with the lycopene group, the composition B and the composition I, the lycopene composition has very obvious difference, and p is less than 0.01.
As can be seen from Table 1, the administration of the compositions A-C, lycopene and composition I can significantly reduce the frequency of urination of the sick rats, reduce the wet weight of the prostate and relieve the disease. Wherein, compared with the lycopene group, the composition B can reduce the times of urination of sick rats and obviously reduce the wet weight of prostate and the prostate index; compared with the composition I, the composition C or the composition A can reduce the times of urination of the sick rats very obviously and reduce the prostate wet weight and the prostate index of the sick rats very obviously. Also, after taking composition A, the number of urination and wet weight of prostate of the diseased rat were similar to those of the normal group.
Test example 2: the medicine is used for treating diabetes insipidus, hypercalcemia, primary aldosteronism or prostatic hyperplasia Study on improvement of frequent nocturia
The subjects are 139 patients with diabetes insipidus, hypercalcemia, primary aldosteronism or prostatic hyperplasia who have frequent nocturia and are not taking medicines in the 20-60 years, and the disease course is more than 3 months. Wherein, 34 cases of diabetes insipidus, 12 cases of a control group, 11 cases of a test I group, 11 cases of a test II group, 9 cases of a final effective number control group, 9 cases of the test I group and 10 cases of the test II group; 28 hypercalcemia cases, 9 cases in a control group, 10 cases in a test I group, 9 cases in a test II group, 8 cases in a final effective number control group, 8 cases in the test I group, and 9 cases in the test II group; 34 cases of primary aldosteronism, 11 cases of a control group, 11 cases of a test I group, 12 cases of a test II group, 10 cases of a final effective number control group, 11 cases of the test I group and 11 cases of the test II group; 43 cases of prostatic hyperplasia, 14 cases of control group and test I group, 15 cases of test II group, 12 cases of final effective number control group, 13 cases of test I group and 14 cases of test II group.
All control groups received daily capsules of soybean oil with an appearance consistent with that of the test groups, all test groups I received daily capsules I from comparative example 1, and all test groups II received daily capsules 3, all with meals, with a test cycle of 1 month, and the number of nocturia times from 10:00pm per day to 6:00am on the next day was recorded before, during and after the test, and the results are shown in Table 2.
TABLE 2
Figure BDA0001422082490000211
Figure BDA0001422082490000221
a: compared with the test group before taking, the medicine has very obvious difference that p is less than 0.01;
b: compared with a control group in half a month, the difference is very obvious, and p is less than 0.01;
c: compared with a control group in one month, the difference is very obvious, and p is less than 0.01;
#: compared with the control group before taking, the traditional Chinese medicine composition has significant difference that p is less than 0.05.
As shown in Table 2, the composition of the present invention has an improvement effect on diabetes insipidus, hypercalcemia, primary aldosteronism and frequent nocturia caused by prostatic hyperplasia, and the improvement effect is very significant for more than half a month after administration. Moreover, compared with the control group in one month, the frequent nocturia symptoms are remarkably improved after the composition is taken for one month; compared with the lycopene medicament in the comparative example 1, the composition has more obvious improvement effect on frequent nocturia symptoms caused by diabetes insipidus, hypercalcemia or primary aldosteronism and prostatic hyperplasia after being taken for half a month or a month.
Test example 3 study of drug safety
(1) Acute oral toxicity of composition a on mice was tested according to the method of "health food test and evaluation technical specification (2003 edition)" page 177, and the results are shown in table 3.
TABLE 3
Figure BDA0001422082490000231
As can be seen from Table 3, after the infection, no toxic symptoms or death of the experimental mice occurred during the observation period. The oral maximum tolerance dose of the male and female sexual urgency of the sample mice is more than 40.0mL/kg body weight.
(2) Acute oral toxicity of composition a on rats was tested according to the method of "health food test and evaluation technical specification (2003 edition)" page 177 with the results shown in table 4.
TABLE 4
Figure BDA0001422082490000232
As can be seen from Table 4, after the infection, no toxic symptoms or death of the experimental rats occurred during the observation period. The female and male sexual urgency oral maximum tolerance dose of the sample rat is more than 40.0mL/kg body weight.
(3) Teratogenicity of mouse sperm was determined according to method page 203 of "health food test and evaluation technical Specification (2003 edition)" with the results shown in Table 5.
TABLE 5
Figure BDA0001422082490000241
#: p is less than 0.05 compared with the negative control group.
As can be seen from Table 5, there was no significant difference in the sperm teratospermia rate between the doses of composition A and the negative control group, and the sample was negative in the mouse teratospermia test.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims (15)

1. A composition, comprising:
Figure FDA0003017411150000011
2. the composition according to claim 1, wherein the lycopene is 80 to 260 parts by weight and the rosemary extract is 0.5 to 4 parts by weight.
3. The composition of claim 1, wherein said vitamin B2And/or 1 to 140 parts by weight of a salt thereof.
4. The composition of claim 1, comprising:
Figure FDA0003017411150000012
5. the composition according to claim 1, characterized by the following items 1) and/or 2):
1) the pharmaceutically or food acceptable zinc-containing compound is at least one selected from zinc sulfate, zinc carbonate, zinc lactate, zinc oxide, zinc gluconate, zinc citrate, zinc glycinate, zinc acetate, zinc chloride and hydrates thereof;
2) the biological zinc is yeast zinc.
6. The composition according to claim 1, wherein the vitamin C and/or the salt thereof is 1 to 2100 parts by weight.
7. The composition according to claim 1, wherein the pharmaceutically or dietetically acceptable zinc-containing compound and/or bio-zinc is 2 to 790 parts by weight.
8. The composition according to claim 1, wherein the vitamin E and/or tocotrienol is 7 to 130 parts by weight.
9. The composition of any one of claims 1 to 8, further comprising an adjuvant.
10. The composition of claim 9, wherein the adjuvant is selected from at least one of diluents, stabilizers, antioxidants, preservatives, binders, glidants, flavoring agents, colorants, wetting agents, anticaking agents, fillers, disintegrants and carriers.
11. A medicament or food product comprising the composition of any one of claims 1 to 10.
12. The food product of claim 11, which is a health food.
13. The drug or food of claim 11, wherein the drug or food is in the form of a capsule, a solid granule or a tablet.
14. A process for preparing a composition according to any one of claims 1 to 10, comprising the steps of:
(1) mixing herba Rosmarini officinalis extract and vitamin B2And/or a salt thereof, vitamin C and/or a salt thereof, a pharmaceutically or food acceptable zinc-containing compound and/or biological zinc, and a diluent to obtain a mixture;
(2) mixing the mixture obtained in step (1), lycopene, at least one selected from diluent, stabilizer and antioxidant, and vitamin E and/or tocotrienol.
15. Use of a composition according to any one of claims 1 to 10 for the preparation of a medicament for the treatment and/or prevention of frequent nocturia symptoms caused by diabetes insipidus, primary aldosteronism, hypercalcemia or prostatic hyperplasia or for the preparation of a medicament for the treatment and/or prevention of prostatic hyperplasia.
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