CN106177964B - The male health-care composition and its formulation preparation method of the zinc gluconate containing folic acid - Google Patents
The male health-care composition and its formulation preparation method of the zinc gluconate containing folic acid Download PDFInfo
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- CN106177964B CN106177964B CN201510213589.8A CN201510213589A CN106177964B CN 106177964 B CN106177964 B CN 106177964B CN 201510213589 A CN201510213589 A CN 201510213589A CN 106177964 B CN106177964 B CN 106177964B
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- China
- Prior art keywords
- folic acid
- zinc gluconate
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- health
- zinc
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- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 title claims abstract description 205
- 235000019152 folic acid Nutrition 0.000 title claims abstract description 104
- 239000011724 folic acid Substances 0.000 title claims abstract description 104
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 title claims abstract description 101
- 229960000304 folic acid Drugs 0.000 title claims abstract description 101
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 title claims abstract description 96
- 235000011478 zinc gluconate Nutrition 0.000 title claims abstract description 91
- 239000011670 zinc gluconate Substances 0.000 title claims abstract description 91
- 229960000306 zinc gluconate Drugs 0.000 title claims abstract description 91
- 239000000203 mixture Substances 0.000 title claims abstract description 59
- 238000002360 preparation method Methods 0.000 title claims abstract description 55
- 238000009472 formulation Methods 0.000 title claims abstract description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 35
- 238000004090 dissolution Methods 0.000 claims abstract description 21
- 230000036541 health Effects 0.000 claims abstract description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 17
- 239000000463 material Substances 0.000 claims abstract description 15
- 239000002775 capsule Substances 0.000 claims abstract description 6
- 229960001407 sodium bicarbonate Drugs 0.000 claims abstract description 6
- 239000007787 solid Substances 0.000 claims abstract description 6
- 239000000843 powder Substances 0.000 claims abstract description 5
- 239000003826 tablet Substances 0.000 claims abstract description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 44
- 235000019359 magnesium stearate Nutrition 0.000 claims description 22
- 239000011701 zinc Substances 0.000 claims description 21
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 20
- 229910052725 zinc Inorganic materials 0.000 claims description 20
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 19
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 19
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 19
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 17
- 229920000881 Modified starch Polymers 0.000 claims description 15
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 239000012467 final product Substances 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 claims 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 235000016804 zinc Nutrition 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 abstract description 11
- 206010067484 Adverse reaction Diseases 0.000 abstract description 10
- 230000006838 adverse reaction Effects 0.000 abstract description 10
- 210000000936 intestine Anatomy 0.000 abstract description 9
- 230000000052 comparative effect Effects 0.000 description 18
- 238000012360 testing method Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- 235000019698 starch Nutrition 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 206010036596 premature ejaculation Diseases 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000008859 change Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 230000007797 corrosion Effects 0.000 description 4
- 238000005260 corrosion Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 208000000509 infertility Diseases 0.000 description 4
- 230000036512 infertility Effects 0.000 description 4
- 241000219095 Vitis Species 0.000 description 3
- 235000009754 Vitis X bourquina Nutrition 0.000 description 3
- 235000012333 Vitis X labruscana Nutrition 0.000 description 3
- 235000014787 Vitis vinifera Nutrition 0.000 description 3
- 206010048259 Zinc deficiency Diseases 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 229940014144 folate Drugs 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 229960003604 testosterone Drugs 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010021929 Infertility male Diseases 0.000 description 2
- 208000007466 Male Infertility Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 206010003883 azoospermia Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- 231100000535 infertility Toxicity 0.000 description 2
- 208000021267 infertility disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- 230000004899 motility Effects 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 206010043298 Testicular atrophy Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003321 atomic absorption spectrophotometry Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
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- 210000000918 epididymis Anatomy 0.000 description 1
- 201000010063 epididymitis Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000009027 insemination Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- JQJCSZOEVBFDKO-UHFFFAOYSA-N lead zinc Chemical compound [Zn].[Pb] JQJCSZOEVBFDKO-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 208000008634 oligospermia Diseases 0.000 description 1
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- 210000002381 plasma Anatomy 0.000 description 1
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- 210000002966 serum Anatomy 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000035911 sexual health Effects 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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- 238000010200 validation analysis Methods 0.000 description 1
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- 235000005074 zinc chloride Nutrition 0.000 description 1
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Abstract
The male health-care composition and its formulation preparation method of present invention offer zinc gluconate containing folic acid, wherein the health composition contains folic acid and zinc gluconate, also comprising acceptable auxiliary material on sodium bicarbonate and galenic pharmacy；The folic acid, zinc gluconate, sodium bicarbonate weight be 0.2-0.8: 35-70: 100-500.Health composition of the present invention can be prepared as being not limited to the oral solid formulation of tablet, capsule, powder, it can be improved folic acid, the dissolution rate of zinc gluconate and degree, the stomach and intestine adverse reaction as caused by zinc gluconate is significantly reduced, and the bioavilability of zinc gluconate can be improved.
Description
Technical field
The present invention relates to the male health-care compositions and its formulation preparation method of the zinc gluconate containing folic acid, and in particular to one
Kind dissolution rate is fast, dissolution rate is high, stomach and intestine adverse reaction is small, the good health composition of bioavilability, belongs to health care product neck
Domain.
Background technique
Premature ejaculation is a kind of common sexual dysfunction disease, not only influences the life quality of patient, over time can shadow
The normal life for ringing man and wife, causes anxiety, anxiety, the fear etc. on patient mental.The undesirable state of mind can be further aggravated
Premature ejaculation, gradually allow patient to lose the confidence, lassitude, to seriously affect its life and work quality.It is multinomial both at home and abroad to grind
Study carefully the results show that Patients with Premature Ejaculation serum folate levels are substantially less than normal male, folate level decline reduces internal 5- hydroxyl color
Amine and NO are horizontal, disturb the ejaculation access of maincenter and periphery, the NO/cGMP dysfunction of urogenital tract are caused, thus most
Cause patient to shorten in the ejaculation latency of intravaginal eventually, physiologically shows as premature ejaculation.
Zinc is the important microelement of human body, in sperm the content of zinc than in blood plasma it is high nearly a hundred times.The shortage meeting of zinc
Lead to orchiatrophy, sperm quantity decline, hypogona dism, serious person even can lose fecundity.Zinc passes through following form
Influence fertility: the 1) manufacture of testosterone: interstitial glands manufacture testosterone needs the effect of a variety of enzymes that could complete, enzyme when zinc-deficiency
It cannot participate in synthesizing, Testosterone will reduce；2) activity of sperm: zinc has the structure and function for keeping spermatoblast film
Effect, motility of sperm reduces and causes infertility when zinc-deficiency；3) influence insemination: zinc concentration reduces in sperm, sperm can be made to lose
Remove fertilizing ability；4) generation of sperm: the seminaferous epithelium of manufacture sperm in testis needs enough zinc and provides raw material, zinc-deficiency
The atrophy of seminaferous epithelium can be caused afterwards, therefore causes oligozoospermia or without sperm.
The World Health Organization points out, the normal couple at child-bearing age, which has 12 months or more, does not take the regular life of contraceptives
And not becoming pregnant can examine as infertility yet.Married couple's sterility incidence about 15%, wherein sterility caused by male factor accounts for
50%, referred to as male sterility, and premature ejaculation and sperm quality obstacle are the major reasons for causing male sterility.Folic acid and zinc are in male
Property normally complete sexual life and sperm quality in terms of play highly important role, therefore, exogenous artificial Supplement of folic acid
More normal couple at child-bearing age will be made to possess perfectly to there are the males of premature ejaculation and sperm quality obstacle to bring income with zinc
Family.
In the prior art, there is Couteat of Folic Acid and zinc gluconate tablets in the market.Couteat of Folic Acid usually has that dissolution rate is low to ask
Therefore topic has only done 45 minutes regulations not less than 75% to its dissolution rate in Chinese Pharmacopoeia 2010 editions, it is well known that living
Property ingredient dissolution rate directly affect its vivo biodistribution availability, and then influence final curative effect.Zinc gluconate tablets are usually deposited
The stomach and intestine adverse reaction such as Nausea and vomiting the problem of, clinical compliance is poor, this generates zinc chloride with zinc gluconate under one's belt
It is related；Meanwhile it is more very important be zinc gluconate bioavailability concerns, usual human body is to wherein active constituent zinc
Bioavilability be about 15%, lead to being largely lost for active constituent in clinical application, be unable to get the effective use of human body.
To sum up, currently there is an urgent need to provide the confession that a kind of dissolved corrosion is good, stomach and intestine adverse reaction is small, bioavilability is high
The alimentation health care composition of child-bearing period male Supplement of folic acid and zinc.
Summary of the invention
It is an object of the present invention to provide the male health-care compositions and its formulation preparation method of the zinc gluconate containing folic acid.
In order to realize these purposes, adopt the following technical scheme that
The male health-care composition of the zinc gluconate containing folic acid, the health composition contain folic acid, zinc gluconate, carbonic acid
Acceptable auxiliary material on hydrogen sodium and galenic pharmacy；The folic acid, zinc gluconate, sodium bicarbonate weight be 0.2-0.8:
35-70∶100-500。
Preferably, the folic acid, zinc gluconate, sodium bicarbonate weight be 0.4-0.8: 35-70: 200-
300。
Acceptable auxiliary material includes filler, adhesive, disintegrating agent, lubricant, corrigent on the galenic pharmacy.
The health composition can be prepared as being not limited to the oral solid formulation of tablet, capsule, powder.
Preferably, the oral solid formulation is tablet.
30 minutes dissolution rates of the folic acid in tablets and zinc gluconate are not less than 85%.
Further, 45 minutes dissolution rates of the folic acid in tablets and zinc gluconate are not less than 95%.
The auxiliary material is microcrystalline cellulose, pregelatinized starch and magnesium stearate, and the parts by weight of the tablet form are as follows: leaf
0.4 part of acid, 70 parts of zinc gluconate, 250 parts of sodium bicarbonate, 60 parts of microcrystalline cellulose, 40 parts of pregelatinized starch, magnesium stearate 5
Part.
The auxiliary material is microcrystalline cellulose, pregelatinized starch and magnesium stearate, and the parts by weight of the tablet form are as follows: leaf
0.8 part of acid, 70 parts of zinc gluconate, 250 parts of sodium bicarbonate, 60 parts of microcrystalline cellulose, 40 parts of pregelatinized starch, magnesium stearate 5
Part.
The health composition formulation preparation method of the zinc gluconate containing folic acid, the tablet can be prepared by following technique and
At:
1) folic acid is crossed into 120 meshes, zinc gluconate crosses 80 meshes, sodium bicarbonate, microcrystalline cellulose, pregelatinized starch,
Magnesium stearate sieves with 100 mesh sieve respectively；
2) folic acid for weighing recipe quantity is uniformly mixed with zinc gluconate using equivalent gradually-increased, then with sodium bicarbonate, micro-
Crystalline cellulose, pregelatinized starch are uniformly mixed；
3) tabletted through tablet press machine by the magnesium stearate total mix of step 2) resulting material and recipe quantity to uniform to obtain the final product.
The invention has the advantages that: the health composition of the zinc gluconate containing folic acid obtained by adopting the above technical scheme, energy
It is enough ideal to generate present invention purpose to be achieved and technical effect, specifically, health composition of the present invention due to
The introducing of sodium bicarbonate can have the following technical effects: 1) dissolved corrosion is good, and bioavilability is high；2) stomach and intestine adverse reaction
Small, clinical compliance is good.
It should be noted that here, in order to enable the more clear errorless understanding of technical field personnel of the present invention
Summary of the invention and technical connotation of the invention, the present inventor are applied to the technical term being related to, symbol
Reagent consumptive material and instrument and equipment do as described below:
" mesh ": refer to the granularity measurement unit stated in Chinese Pharmacopoeia 2010 editions；
" instrument and equipment ": no special instruction is commercially available routine instrument device；
" auxiliary material reagent ": no special instruction is commercially available conventional reagent consumptive material；
" Tmax ": time when drug after medicine reaches maximum plasma concentration is showed；
" Cmax ": the maximum plasma concentration detected after medicine in body is showed；
“AUC0~∞": refer to lower area of blood concentration-time curve, during bioavailability study, in dosage
Under the premise of identical, which then illustrates bioavilability height, and the numerical value is low to illustrate that bioavilability is low, needs furtherly
Bright, the height of bioavilability of the present invention is indicated using the height of this numerical value.
Specific embodiment
In the following, the personnel for the ease of the technical field of the invention understand that the present invention, the present invention provide following specific real
Mode is applied to be described further the health composition of the zinc gluconate containing folic acid:
Embodiment 1
The preparation of the male health-care composition tablet of the zinc gluconate containing folic acid:
Preparation prescription:
| Supplementary material | Recipe quantity (10000) |
| Folic acid | 4.0g |
| Zinc gluconate | 700g |
| Sodium bicarbonate | 2500g |
| Microcrystalline cellulose | 600g |
| Pre-paying starch | 400g |
| Magnesium stearate | 50g |
Preparation process:
1) folic acid is crossed into 120 meshes, zinc gluconate crosses 80 meshes, sodium bicarbonate, microcrystalline cellulose, pregelatinized starch,
Magnesium stearate sieves with 100 mesh sieve respectively；
2) folic acid for weighing recipe quantity is uniformly mixed with zinc gluconate using equivalent gradually-increased, then with sodium bicarbonate, micro-
Crystalline cellulose, pregelatinized starch are uniformly mixed；
3) tabletted through tablet press machine by the magnesium stearate total mix of step 2) resulting material and recipe quantity to uniform to obtain the final product.
Embodiment 2
The preparation of the male health-care composition tablet of the zinc gluconate containing folic acid:
Preparation prescription:
| Supplementary material | Recipe quantity (10000) |
| Folic acid | 8.0g |
| Zinc gluconate | 700g |
| Sodium bicarbonate | 2500g |
| Microcrystalline cellulose | 600g |
| Pre-paying starch | 400g |
| Magnesium stearate | 50g |
Preparation process: with embodiment 1.
Embodiment 3
The preparation of the male health-care composition tablet of the zinc gluconate containing folic acid:
Preparation prescription:
| Supplementary material | Recipe quantity (10000) |
| Folic acid | 2.0g |
| Zinc gluconate | 350g |
| Sodium bicarbonate | 2000g |
| Microcrystalline cellulose | 500g |
| Pre-paying starch | 500g |
| Magnesium stearate | 40g |
Preparation process: with embodiment 1.
Embodiment 4
The preparation of the male health-care composition tablet of the zinc gluconate containing folic acid:
Preparation prescription:
| Supplementary material | Recipe quantity (10000) |
| Folic acid | 4.0g |
| Zinc gluconate | 500g |
| Sodium bicarbonate | 3000g |
| Microcrystalline cellulose | 500g |
| Pre-paying starch | 500g |
| Magnesium stearate | 40g |
Preparation process: with embodiment 1.
Embodiment 5
The preparation of the male health-care composition capsule of the zinc gluconate containing folic acid:
Preparation prescription:
| Supplementary material | Recipe quantity (10000) |
| Folic acid | 4.0g |
| Zinc gluconate | 700g |
| Sodium bicarbonate | 5000g |
| Microcrystalline cellulose | 600g |
| Pre-paying starch | 400g |
| Magnesium stearate | 50g |
Preparation process: with the preparation process of the male health-care composition tablet of the zinc gluconate containing folic acid in embodiment 1, no
Same is by resulting material in final step by the tabletted male for being adjusted to be filled with capsule to get the zinc gluconate containing folic acid
Sexual health composition capsule.
Embodiment 6
The preparation of the male health-care combination composition powders of the zinc gluconate containing folic acid:
Preparation prescription:
| Supplementary material | Recipe quantity (10000 bags) |
| Folic acid | 4.0g |
| Zinc gluconate | 500g |
| Sodium bicarbonate | 1000g |
| Sucrose | 400.0g |
| Mannitol | 600.0g |
| Corrigent | 60.0g |
| Magnesium stearate | 40.0 |
Preparation process: with the preparation process of the male health-care composition tablet of the zinc gluconate containing folic acid in embodiment 1, no
Be final step by resulting material by it is tabletted be adjusted to it is filling into compound membrane bag to get gluconic acid containing folic acid
The male health-care of zinc combines composition powders.
Comparative example 1
The preparation (being free of sodium bicarbonate) of the male health-care composition tablet of the zinc gluconate containing folic acid:
Preparation prescription:
| Supplementary material | Recipe quantity (10000) |
| Folic acid | 4.0g |
| Zinc gluconate | 700g |
| Starch | 2500g |
| Microcrystalline cellulose | 600g |
| Pre-paying starch | 400g |
| Magnesium stearate | 50g |
Preparation process: 1) crossing 120 meshes for folic acid, and zinc gluconate crosses 80 meshes, microcrystalline cellulose, pregelatinized starch,
Magnesium stearate sieves with 100 mesh sieve respectively；
2) folic acid for weighing recipe quantity is uniformly mixed with zinc gluconate using equivalent gradually-increased, then fine with starch, crystallite
Dimension element, pregelatinized starch are uniformly mixed；
3) tabletted through tablet press machine by the magnesium stearate total mix of step 2) resulting material and recipe quantity to uniform to obtain the final product.
Test case 1
1 gained preparation dissolution test of embodiment 1-6 and comparative example:
According under Couteat of Folic Acid item in 2010 addendum of Chinese Pharmacopoeia and in Chinese Pharmacopoeia 2010 editions under zinc gluconate tablets item
The inspection method of dissolution rate, respectively carry out embodiment 1-6, comparative example 1, commercially available Couteat of Folic Acid (Jiangxi Pharmaceutical Co. Ltd.),
Folic acid in preparation obtained by commercial glucose saccharic acid zinc metal sheet (HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory), 30 minutes of zinc gluconate, 45 minutes it is molten
Out-degree inspection, as a result as shown in table 1 below:
1 gained preparation dissolution test result of 1. embodiment 1-6 of table and comparative example
1 interpretation of result of table in synthesis is it is found that 1) folic acid gluconic acid zinc preparation middle period obtained by embodiment 1-6 of the present invention
30 minutes dissolution rates of acid and zinc gluconate in 85% or more, 45 minute dissolution rate 95% or more, with comparative example and
Commercially available Couteat of Folic Acid, zinc gluconate tablets are compared, and have faster dissolution rate and higher dissolution degree, while prompting may tool
There is excellent vivo biodistribution availability；2) in 1 gained folic acid gluconic acid zinc preparation of comparative example and commercially available Couteat of Folic Acid and glucose
In sour zinc metal sheet 30 minutes dissolution rates of folic acid and zinc gluconate 70% hereinafter, 45 minutes dissolution rates 80% hereinafter,
It is well known that for oral solid formulation, active constituent dissolution rate in vivo and dissolution degree be it is very crucial,
The difference of dissolution degree and speed directly results in the similarities and differences of clinical efficacy, and active constituent is difficult to dissolve out often vivo biodistribution utilization
Spend the major reason of difference；
For synthesis, the preparation of the present invention containing folic acid, zinc gluconate, wherein the introducing of sodium bicarbonate, is brought
Folic acid and zinc gluconate dissolution rate and degree significantly improves in final preparation.The present inventor thinks that this can
It can be since the introducing of sodium bicarbonate generates, being introduced into for sodium bicarbonate improves gained preparation moisture and work in process in leaching
Property ingredient between micro change, such as in microenvironment pH value change, microcosmic wetting, disintegration behavior change etc., although
Concrete reason can not determine, but its bring accident technical effect is pleasurable.
Test case 2
Referring to the method in existing " chemicals stability study technological guidance principle " and condition is investigated, according to middle traditional Chinese medicines
Couteat of Folic Acid, the content under zinc gluconate tablets item, 45 minutes dissolution test methods in 2010 addendum of allusion quotation carry out embodiment 1-
Steadiness under 6 gained preparation acceleration environments is investigated, as a result such as the following table 2.
Preparation accelerated stability result obtained by 2. embodiment 1-6 of table
2 interpretation of result of table in synthesis is it is found that preparation obtained by 1-6 of the embodiment of the present invention is accelerating to be able to maintain within 6 months well
Stability, the content and dissolved corrosion of folic acid and zinc gluconate do not substantially change.
Test case 3
In order to study 1 gained preparation of embodiment 1 and comparative example of the present invention and commercially available Couteat of Folic Acid (the limited duty of Jiangxi pharmacy
Ren company) and zinc gluconate tablets (HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory) bioavilability situation, the present inventor select
Beagle dog as animal subject carry out bioavilability comparative study, need it is predeclared be, following testing programs
Implement the raising of Beagle dog in whole cycle and be all made of same standardized diet, result may be brought with excluding food
Adverse effect.
Animal selection: selecting female, health, Beagle dog of the same age, and weight amounts to 18 within the scope of 10 ± 2.0kg,
It is randomly divided into 3 groups, every group 6.
Testing program: 1) it tests first 14 day and does not apply any both effectiveness substance；2) it is tested dynamic to test preceding 1 day 18:00 each group
Object is fasted, and test same day 6:00 give the folic acid of 0.2mg/kg weight and the zinc gluconate of 35mg/kg weight on an empty stomach, and
In each sampling time point (0 point, 15 minutes, 30 minutes, 45 minutes, 1.0 hours, 1.5 hours, 2.0 hours, 4.0 hours, it is 8.0 small
When, 12.0 hours, 24.0 hours), extract forelimb median vein 2mL blood keep sample；4) commercially available Beagle dog folic acid ELISA is used
Kit carries out folate content detection to the sample of each sampling time point of each tested group of animal, using atomic absorption spectrophotometry
Zn content detection is carried out to the sample of each sampling time point of each tested group of animal；And calculate each tested group 6 Beagle dogs are each
The mean value of assessment item, it need to be noted that be sample analysis detection before, the present inventor is to detection method used
Precision, the rate of recovery, specificity, detection limit etc. carried out the methodology validation of system, the results showed that, which is section
It learns feasible.
Using the result such as the following table 3 for the Beagle dog bioavailability study that this test case carries out:
3. embodiment 1 of table, comparative example 1 and commercial preparation bioavailability study result
3 interpretation of result of table in synthesis is it is found that 1) 1 preparation of embodiment of the zinc gluconate of the present invention containing folic acid, to leaf
The infiltration rate of acid and zinc gluconate faster, shows as the Tmax=45 minute of folic acid, the Tmax=1.5 hour of zinc；And it is right
Ratio 1 and commercially available Couteat of Folic Acid+zinc gluconate tablets, the Tmax=1.0 hour of folic acid, the Tmax=2.0 hour of zinc.2) embodiment
The bioavilability of 1 gained folic acid zinc gluconate tablets is apparently higher than comparative example 1 and commercial preparation, for zinc gluconate,
(4157.0-3389.6)/3789.6=22.6% is improved for 1 relative contrast's example 1 of embodiment, relatively commercially available Couteat of Folic Acid+Portugal
(4157.0-3315.3)/3315.3=25.4% is improved for grape saccharic acid zinc metal sheet.
It should be noted that the present inventor prepares gained to embodiment 2-6 according further to the method in this test case
Folic acid gluconic acid zinc preparation carried out bioavailability study, as a result show to be equal with embodiment 1 or close situation.
Test case 4
The present inventor " adds the poly- smart diet therapy soup of taste to few essence, weak essence referring to what 2009 Nian Yuxin Journals of Traditional Chinese Medicine were delivered
The experimental study that sperm quality influences in a disease rat epididymis " method described in text, to gluconic acid containing folic acid of the present invention
1 gained preparation of embodiment, 1 preparation of comparative example and commercially available Couteat of Folic Acid+zinc gluconate tablets of the health composition preparation of zinc carry out
Research, in addition to normal group and model group, the grape of each tested group of folic acid for giving 0.1mg/kg weight and 17.5mg/kg weight
Saccharic acid zinc, as a result as shown in table 4 below.
4. embodiment 1 of table, comparative example 1 and commercial preparation Ergonomy result of study
Note: the 1. p < 0.05 compared with normal group；The 2. p < 0.05 compared with comparative example 1；With Couteat of Folic Acid+zinc gluconate tablets
Than 3. p < 0.05.
4 interpretation of result of table in synthesis is it is found that 1 gained folic acid zinc gluconate tablets of embodiment of the present invention can significantly change
Kind few essence, azoospermia, compared with comparative example 1 and commercial preparation, embodiment 1 is mentioned for sperm concentration, A grades of sperms and total motility rate
High performance is obvious, and has significant statistical significance.System of the present invention containing folic acid, zinc gluconate and sodium bicarbonate
Agent is finally reflected being obviously improved for effect due to the dissolved corrosion of folic acid and zinc gluconate, the improvement of bioavilability.
It should be noted that the present inventor prepares gained to embodiment 2-6 according further to the method in this test case
Folic acid gluconic acid zinc preparation carried out Ergonomy research, as a result show to be equal with embodiment 1 or close situation.
Test case 5
The small beneficial effect of the health composition bring stomach and intestine adverse reaction in order to further illustrate the present invention, this survey
Examination example has carried out the comparative study of clinical test-meal experiment to embodiment 1, comparative example 1 and commercially available Couteat of Folic Acid and zinc gluconate tablets.
Subject's selection: selection is without the bad daily hobby such as smoke, drink, the healthy adult male of no gastrointestinal disease history,
Age between 20-30 years old, amounts to 300, is randomly divided into three groups, every group 100.
Test-meal scheme: each group subject gave 0.4mg folic acid, 70mg zinc gluconate dosage in the test-meal same day on an empty stomach
Tested material, continuous test-meal 14 days record the stomach and intestine adverse reaction situation after subject's test-meal daily.
Observation index: mainly to each group tested patients, whether there is or not Nausea and vomiting, stomachache, abdominal pain phenomenons to record.
5. embodiment 1 of table, comparative example 1 and commercial preparation stomach and intestine adverse reaction result of study
5 interpretation of result of table in synthesis is it is found that reality prepared by the health composition of the zinc gluconate of the present invention containing folic acid
1 folic acid zinc gluconate tablets of example are applied, compared with comparative example 1 and commercial preparation, hence it is evident that the adverse reaction for reducing subject occurs
Rate, direct bring income are that the clinical compliance of patient is improved, this is for needing long-term supplemented with exogenous folic acid and Portugal
It is highly beneficial for the crowd of grape saccharic acid zinc.
It should be noted that the present inventor prepares gained to embodiment 2-6 according further to the method in this test case
Folic acid gluconic acid zinc preparation carried out stomach and intestine adverse reaction research, as a result show to be equal with embodiment 1 or close feelings
Shape.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, without departing from the technical principles of the invention, several improvements and modifications, these improvements and modifications can also be made
Also it should be regarded as protection scope of the present invention.
Claims (9)
1. the male health-care composition of the zinc gluconate containing folic acid, which is characterized in that the health composition is by folic acid, glucose
Sour zinc, sodium bicarbonate, microcrystalline cellulose, pregelatinized starch and magnesium stearate composition, or by folic acid, zinc gluconate, bicarbonate
Sodium, sucrose, mannitol, corrigent and magnesium stearate composition, the weight of the folic acid, zinc gluconate, sodium bicarbonate
For 0.2-0.8:35-70:100-500.
2. the male health-care composition of the zinc gluconate containing folic acid according to claim 1, which is characterized in that the folic acid,
Zinc gluconate, sodium bicarbonate weight be 0.4-0.8:35-70:200-300.
3. the male health-care composition of the zinc gluconate containing folic acid according to claim 1, which is characterized in that the health care group
Close the oral solid formulation that object can be prepared as tablet, capsule, powder.
4. the health composition of the zinc gluconate containing folic acid according to claim 3, which is characterized in that the oral administration solid system
Agent is tablet.
5. the male health-care composition of the zinc gluconate containing folic acid according to claim 4, which is characterized in that in the tablet
30 minutes dissolution rates of folic acid and zinc gluconate are not less than 85%.
6. the male health-care composition of the zinc gluconate containing folic acid according to claim 4, which is characterized in that in the tablet
45 minutes dissolution rates of folic acid and zinc gluconate are not less than 95%.
7. the male health-care composition of the zinc gluconate containing folic acid according to claim 4, which is characterized in that the tablet
Parts by weight composition are as follows: 0.4 part of folic acid, 70 parts of zinc gluconate, 250 parts of sodium bicarbonate, 60 parts of microcrystalline cellulose, pregelatinized starch
40 parts, 5 parts of magnesium stearate.
8. the male health-care composition of the zinc gluconate containing folic acid according to claim 4, which is characterized in that the tablet
Parts by weight composition are as follows: 0.8 part of folic acid, 70 parts of zinc gluconate, 250 parts of sodium bicarbonate, 60 parts of microcrystalline cellulose, pregelatinized starch
40 parts, 5 parts of magnesium stearate.
9. a kind of preparation method of the male health-care composition of claim 7 or 8 zinc gluconate containing folic acid, feature exist
In the tablet can be prepared by following technique:
1) folic acid is crossed into 120 meshes, zinc gluconate crosses 80 meshes, sodium bicarbonate, microcrystalline cellulose, pregelatinized starch, tristearin
Sour magnesium sieves with 100 mesh sieve respectively；
2) folic acid for weighing recipe quantity is uniformly mixed with zinc gluconate using equivalent gradually-increased, then fine with sodium bicarbonate, crystallite
Dimension element, pregelatinized starch are uniformly mixed；
3) tabletted through tablet press machine by the magnesium stearate total mix of step 2 resulting material and recipe quantity to uniform to obtain the final product.
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Denomination of invention: Male health care composition containing zinc folate gluconate and preparation method thereof Effective date of registration: 20210818 Granted publication date: 20190507 Pledgee: Beijing Yizhuang International Financing Guarantee Co.,Ltd. Pledgor: BEIJING SILIAN PHARMACEUTICAL INDUSTRY Co.,Ltd. Registration number: Y2021990000732 |
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