CN106177964A - Male health-care compositions containing folic acid zinc gluconate and formulation preparation method thereof - Google Patents
Male health-care compositions containing folic acid zinc gluconate and formulation preparation method thereof Download PDFInfo
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- CN106177964A CN106177964A CN201510213589.8A CN201510213589A CN106177964A CN 106177964 A CN106177964 A CN 106177964A CN 201510213589 A CN201510213589 A CN 201510213589A CN 106177964 A CN106177964 A CN 106177964A
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- CN
- China
- Prior art keywords
- folic acid
- zinc gluconate
- care compositions
- health
- compositions containing
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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 189
- 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 97
- 235000019152 folic acid Nutrition 0.000 title claims abstract description 97
- 239000011724 folic acid Substances 0.000 title claims abstract description 97
- 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 94
- 229960000304 folic acid Drugs 0.000 title claims abstract description 94
- 239000011670 zinc gluconate Substances 0.000 title claims abstract description 93
- 235000011478 zinc gluconate Nutrition 0.000 title claims abstract description 93
- 229960000306 zinc gluconate Drugs 0.000 title claims abstract description 93
- 239000000203 mixture Substances 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 56
- 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 46
- 238000004090 dissolution Methods 0.000 claims abstract description 24
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 23
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 23
- 230000036541 health Effects 0.000 claims abstract description 18
- 239000002671 adjuvant Substances 0.000 claims abstract description 10
- 239000002775 capsule Substances 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 46
- 238000000034 method Methods 0.000 claims description 24
- 235000019359 magnesium stearate Nutrition 0.000 claims description 23
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 22
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 22
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 22
- 229940016286 microcrystalline cellulose Drugs 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
- 229920000881 Modified starch Polymers 0.000 claims description 14
- 229920002472 Starch Polymers 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 10
- 239000008107 starch Substances 0.000 claims description 10
- 235000019698 starch Nutrition 0.000 claims description 10
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- 239000012467 final product Substances 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- 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 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229960001407 sodium bicarbonate Drugs 0.000 claims description 3
- 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 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 125000003929 folic acid group Chemical group 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000006068 taste-masking agent Substances 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 1
- 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 1
- 238000006243 chemical reaction Methods 0.000 abstract description 9
- 230000002496 gastric effect Effects 0.000 abstract description 9
- 230000000052 comparative effect Effects 0.000 description 19
- 238000012360 testing method Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 9
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 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
- 230000037396 body weight Effects 0.000 description 6
- 206010036596 premature ejaculation Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 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 4
- 238000001514 detection method Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000000174 gluconic acid Substances 0.000 description 4
- 235000012208 gluconic acid Nutrition 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 3
- 206010048259 Zinc deficiency Diseases 0.000 description 3
- 206010003883 azoospermia Diseases 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000007797 corrosion Effects 0.000 description 3
- 238000005260 corrosion Methods 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 229940014144 folate Drugs 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- 229960003604 testosterone Drugs 0.000 description 3
- 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 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000005911 diet Nutrition 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
- 230000006872 improvement Effects 0.000 description 2
- 208000000509 infertility Diseases 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 231100000535 infertility Toxicity 0.000 description 2
- 230000009027 insemination Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 230000000920 spermatogeneic effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 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
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 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 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 description 1
- 206010043298 Testicular atrophy Diseases 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 201000010788 atrophy of testis Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 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
- 230000002354 daily effect Effects 0.000 description 1
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- 208000010643 digestive system disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
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- 238000001727 in vivo Methods 0.000 description 1
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- 210000002570 interstitial cell Anatomy 0.000 description 1
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- 238000002386 leaching Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 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
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides the male health-care compositions containing folic acid zinc gluconate and formulation preparation method thereof, and wherein, described health composition contains folic acid and zinc gluconate, also comprises acceptable adjuvant on sodium bicarbonate and galenic pharmacy；Described folic acid, zinc gluconate, the weight of sodium bicarbonate are 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, folic acid, the dissolution rate of zinc gluconate and degree can be improved, significantly reduce the gastrointestinal untoward reaction caused by zinc gluconate, and the bioavailability of zinc gluconate can be improved.
Description
Technical field
The present invention relates to the male health-care compositions containing folic acid zinc gluconate and formulation preparation method thereof, tool
Body relates to the health care that a kind of dissolution rate is fast, dissolution is high, gastrointestinal untoward reaction is little, bioavailability is good
Compositions, belongs to field of health care products.
Background technology
Premature ejaculation is a kind of common sexual dysfunction disease, not only affects the life quality of patient, long and long
The orthobiosis that can affect man and wife, cause the anxiety on patient mental, anxiety, fear etc..Bad essence
God's state can increase the weight of premature ejaculation further, and the patient that allows gradually loses the confidence, lassitude, thus has a strong impact on
Its live and work quality.Domestic and international multinomial result of study shows, Patients with Premature Ejaculation serum folate levels is the lowest
In normal male, folate level declines, and reduces internal 5-hydroxy tryptamine and NO level, disturb maincenter and
The ejaculation path of periphery, causes the NO/cGMP dysfunction of urogenital tract, thus ultimately results in patient and exist
Intravaginal ejaculation latency shortens, and physiologically shows as premature ejaculation.
Zinc is the trace element that body weight for humans is wanted, in seminal fluid the content of zinc than in blood plasma high nearly a hundred times.Zinc
Shortage can cause atrophy of testis, sperm quantity to decline, sexual hypofunction, and severe patient even can lose fertility energy
Power.Zinc affects fertility by following form: the 1) manufacture of testosterone: interstitial cell manufactures testosterone and needs
The effect wanting multiple enzyme just can complete, and during zinc deficiency, enzyme cannot participate in synthesis, and Testosterone will reduce；
2) activity of sperm: zinc has structure and the effect of function, sperm motility during zinc deficiency keeping spermatid film
Power reduces and causes sterile；3) impact insemination: in seminal fluid, zinc concentration reduces, and sperm can be made to lose insemination energy
Power；4) generation of sperm: manufacture the spermatogenic epithelium of sperm in testis, it is desirable to have enough zinc provides raw material,
The atrophy of spermatogenic epithelium can be caused after zinc deficiency, thus result in oligospermia or without sperm.
World Health Organization (WHO) points out, the normal couple at child-bearing age have more than 12 months do not take contraceptives regular
Sexual life and do not become pregnant yet and can examine as sterile.Married couple infertility incidence rate about 15%, wherein male because of
The infertility that element causes accounts for 50%, referred to as male infertility, and premature ejaculation and sperm quality obstacle are to cause male
Sterile major reason.Folic acid and zinc play very in terms of male normally completes sexual life and sperm quality
Important role, therefore, ectogenic artificial Supplement of folic acid and zinc will be given and there is premature ejaculation and sperm quality barrier
The male hindered brings income, makes the more normal couple at child-bearing age have perfect family.
In prior art, market exists YESUAN PIAN and zinc gluconate tablets.YESUAN PIAN is usually present dissolution
Low problem, therefore, has only done 45 minutes its dissolution in Chinese Pharmacopoeia 2010 editions and has been not less than 75%
Regulation, it is well known that the dissolution of active component directly affects its vivo biodistribution availability, and then impact
Final curative effect.Zinc gluconate tablets is usually present the problem of the gastrointestinal untoward reaction such as Nausea and vomiting, clinical
Compliance is poor, and it is relevant that this generates zinc chloride under one's belt with zinc gluconate；Meanwhile, the most very important
Being the bioavailability concerns of zinc gluconate, usual human body is to the bioavailability of wherein active component zinc about
It is 15%, causes a large amount of losses of active component in clinical practice, it is impossible to obtain effective utilization of human body.
To sum up, currently in the urgent need to providing, a kind of dissolved corrosion is good, gastrointestinal untoward reaction is little, biological utilisation
Spend high confession child-bearing period male's Supplement of folic acid and the alimentation health care composition of zinc.
Summary of the invention
It is an object of the present invention to provide the male health-care compositions containing folic acid zinc gluconate and preparation preparation side thereof
Method.
In order to realize these purposes, adopt the following technical scheme that
Male health-care compositions containing folic acid zinc gluconate, described health composition contains folic acid, gluconic acid
Acceptable adjuvant on zinc, sodium bicarbonate and galenic pharmacy；Described folic acid, zinc gluconate, sodium bicarbonate
Weight is 0.2-0.8: 35-70: 100-500.
Preferably, described folic acid, zinc gluconate, the weight of sodium bicarbonate are
0.4-0.8∶35-70∶200-300。
On described galenic pharmacy, acceptable adjuvant includes filler, binding agent, disintegrating agent, lubricant, taste masking
Agent.
Described health composition can be prepared as being not limited to the oral solid formulation of tablet, capsule, powder.
Preferably, described oral solid formulation is tablet.
30 minutes dissolutions of described folic acid in tablets and zinc gluconate are not less than 85%.
Further, 45 minutes dissolutions of described folic acid in tablets and zinc gluconate are not less than 95%.
Described adjuvant is microcrystalline Cellulose, pregelatinized Starch and magnesium stearate, the weight portion group of described tablet
Become: 0.4 part of folic acid, zinc gluconate 70 parts, sodium bicarbonate 250 parts, microcrystalline Cellulose 60 parts,
Pregelatinized Starch 40 parts, magnesium stearate 5 parts.
Described adjuvant is microcrystalline Cellulose, pregelatinized Starch and magnesium stearate, the weight portion group of described tablet
Become: 0.8 part of folic acid, zinc gluconate 70 parts, sodium bicarbonate 250 parts, microcrystalline Cellulose 60 parts,
Pregelatinized Starch 40 parts, magnesium stearate 5 parts.
Health composition formulation preparation method containing folic acid zinc gluconate, described tablet can be by following technique system
For forming:
1) folic acid being crossed 120 mesh sieves, zinc gluconate crosses 80 mesh sieves, sodium bicarbonate, microcrystalline Cellulose,
Pregelatinized Starch, magnesium stearate cross 100 mesh sieves respectively；
2) weighing the folic acid of recipe quantity uses the equivalent method of progressively increasing to mix homogeneously with zinc gluconate, then with carbonic acid
Hydrogen sodium, microcrystalline Cellulose, pregelatinized Starch mix homogeneously；
3) by step 2) magnesium stearate of gained material and recipe quantity always mixes to uniformly, is pressed into through tablet machine
Sheet and get final product.
The method have the benefit that the health-care combination containing folic acid zinc gluconate using technique scheme to obtain
Thing, it is possible to preferably produce present invention purpose to be reached and technique effect, specifically, institute of the present invention
State health composition and can produce following technique effect due to the introducing of sodium bicarbonate: 1) dissolved corrosion is good,
Bioavailability is high；2) gastrointestinal untoward reaction is little, and clinical compliance is good.
It should be noted that here, in order to enable technical field personnel of the present invention more clear errorless
The summary of the invention understanding the present invention and technical connotation, the present inventor is to the described professional art related to
Language, symbol, the reagent consumptive material being applied to and instrument and equipment do as described below:
" mesh ": refer to the granularity measurement unit stated in Chinese Pharmacopoeia 2010 editions；
" instrument and equipment ": be commercially available routine instrument device without special instruction；
" adjuvant reagent ": be commercially available conventional reagent consumptive material without special instruction；
" Tmax ": time when medicine reaches maximum plasma concentration after showing medicine；
" Cmax ": the maximum plasma concentration detected in body after showing medicine；
“AUC0～∞": refer to lower area of blood concentration-time curve, during bioavailability study, giving
On the premise of pharmaceutical quantities is identical, this numerical value height then illustrates that bioavailability is high, this numerical value low explanation biological utilisation
Spend low, need it is further noted that the height of bioavailability of the present invention uses the height of this numerical value
Represent.
Detailed description of the invention
Below, the personnel for the ease of the technical field of the invention understand that the present invention, the present invention provide as follows
The described health composition containing folic acid zinc gluconate is described further by detailed description of the invention:
Embodiment 1
The preparation of the male health-care composition tablet containing folic acid zinc gluconate:
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 technology:
1) folic acid being crossed 120 mesh sieves, zinc gluconate crosses 80 mesh sieves, sodium bicarbonate, microcrystalline Cellulose,
Pregelatinized Starch, magnesium stearate cross 100 mesh sieves respectively；
2) weighing the folic acid of recipe quantity uses the equivalent method of progressively increasing to mix homogeneously with zinc gluconate, then with carbonic acid
Hydrogen sodium, microcrystalline Cellulose, pregelatinized Starch mix homogeneously；
3) by step 2) magnesium stearate of gained material and recipe quantity always mixes to uniformly, is pressed into through tablet machine
Sheet and get final product.
Embodiment 2
The preparation of the male health-care composition tablet containing folic acid zinc gluconate:
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 technology: with embodiment 1.
Embodiment 3
The preparation of the male health-care composition tablet containing folic acid zinc gluconate:
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 technology: with embodiment 1.
Embodiment 4
The preparation of the male health-care composition tablet containing folic acid zinc gluconate:
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 technology: with embodiment 1.
Embodiment 5
The preparation of the male health-care composition capsule containing folic acid zinc gluconate:
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 technology: with the preparation of the male health-care composition tablet containing folic acid zinc gluconate in embodiment 1
Technique, is except for the difference that adjusted to gained material by tabletted in final step and is filled to capsule, must contain
The male health-care composition capsule of folic acid zinc gluconate.
Embodiment 6
The preparation of the male health-care compositions powder containing folic acid zinc gluconate:
Preparation prescription:
| Supplementary material | Recipe quantity (10000 bags) |
| Folic acid | 4.0g |
| Zinc gluconate | 500g |
| Sodium bicarbonate | 1000g |
| Sucrose | 400.0g |
| Mannitol | 600.0g |
| Correctives | 60.0g |
| Magnesium stearate | 40.0 |
Preparation technology: with the preparation of the male health-care composition tablet containing folic acid zinc gluconate in embodiment 1
Technique, is except for the difference that adjusted to fill in compound membrane bag in final step by gained material by tabletted,
Obtain the male health-care compositions powder containing folic acid zinc gluconate.
Comparative example 1
The preparation (without sodium bicarbonate) of the male health-care composition tablet containing folic acid zinc gluconate:
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 technology: 1) folic acid crossed 120 mesh sieves, zinc gluconate crosses 80 mesh sieves, microcrystalline Cellulose,
Pregelatinized Starch, magnesium stearate cross 100 mesh sieves respectively；
2) weighing the folic acid of recipe quantity uses the equivalent method of progressively increasing to mix homogeneously with zinc gluconate, then with starch,
Microcrystalline Cellulose, pregelatinized Starch mix homogeneously；
3) by step 2) magnesium stearate of gained material and recipe quantity always mixes to uniformly, is pressed into through tablet machine
Sheet and get final product.
Test case 1
Embodiment 1-6 and comparative example 1 gained preparation dissolution test:
According under Chinese Pharmacopoeia 2010 addendum Folic Acid sheet item and Chinese Pharmacopoeia 2010 editions in zinc gluconate
The inspection method of dissolution under sheet item, carries out embodiment 1-6, comparative example 1, commercially available YESUAN PIAN (river respectively
Western Pharmaceutical Co), in commercial glucose saccharic acid zinc metal sheet (HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory) gained preparation
Folic acid, 30 minutes of zinc gluconate, 45 minutes dissolution tests, result is as shown in table 1 below:
Table 1. embodiment 1-6 and comparative example 1 gained preparation dissolution test result
Comprehensive upper table 1 interpretation of result understands, and 1) embodiment 1-6 gained folic acid gluconic acid of the present invention
30 minutes dissolutions of zinc preparation Folic Acid and zinc gluconate are all more than 85%, and within 45 minutes, dissolution is equal
More than 95%, compare with commercially available YESUAN PIAN, zinc gluconate tablets with comparative example, there is the speed of dissolution faster
Degree and higher dissolution degree, prompting simultaneously is likely to be of excellent vivo biodistribution availability；2) comparative example 1
In gained folic acid gluconic acid zinc preparation and commercially available YESUAN PIAN and zinc gluconate tablets Folic Acid and gluconic acid
30 minutes dissolutions of zinc are all below 70%, and within 45 minutes, dissolution is all below 80%, it is well known that right
From the point of view of oral solid formulation, active component dissolution rate in vivo and dissolution degree are the most crucial,
The difference of dissolution degree and speed directly results in the similarities and differences of clinical efficacy, and it is often body that active component is difficult to dissolution
The major reason of interior poor bioavailability；
From the point of view of comprehensively, of the present invention containing folic acid, the preparation of zinc gluconate, the wherein introducing of sodium bicarbonate,
Bring significantly improving of final preparation Folic Acid and zinc gluconate dissolution rate and degree.The present invention's
It has been recognised by the inventors that what this introducing being likely due to sodium bicarbonate produced, the introducing of sodium bicarbonate improves institute
Preparation pH value in the change of micro environment, such as microenvironment between moisture and active component in process in leaching
Change, microcosmic moistening, the change etc. of disintegrate behavior, although concrete reason cannot determine, but what it brought
Unexpected technique effect is pleasurable.
Test case 2
With reference to the method in existing " chemicals stability study technological guidance's principle " and the condition of investigation, press
According to the content under Chinese Pharmacopoeia 2010 addendum Folic Acid sheet, zinc gluconate tablets item, 45 minutes dissolutions
Inspection method, carries out the steadiness under embodiment 1-6 gained preparation acceleration environment and investigates, and result is as follows
Table 2.
Table 2. embodiment 1-6 gained preparation accelerated stability result
Comprehensive upper table 2 interpretation of result understands, and embodiment of the present invention 1-6 gained preparation 6 months can in acceleration
Good stability, folic acid and the content of zinc gluconate and dissolved corrosion is kept all not to occur substantially to change.
Test case 3
In order to study embodiment 1 of the present invention and comparative example 1 gained preparation and commercially available YESUAN PIAN (Jiangxi system
Medicine Co., Ltd) and the bioavailability situation of zinc gluconate tablets (HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory),
The present inventor selects Beagle dog to carry out the comparative study of bioavailability as animal subject, needs
Wanting predeclared, the raising of Beagle dog in the whole cycle that is implemented in of following testing program all uses
Same standardized diet, to get rid of the adverse effect that result may be brought by food.
Animal selects: selecting Beagle dog female, healthy, of the same age, body weight is all in 10 ± 2.0kg scope
In, 18 altogether, it is randomly divided into 3 groups, often group 6.
Testing program: 1) test first 14 days and do not use any both effectiveness material；2) first 1 day 18:00 is tested
Each group animal subject starts fasting, and test 6:00 on the same day gives folic acid and the 35mg of 0.2mg/kg body weight on an empty stomach
The zinc gluconate of/kg body weight, 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, 8.0 hours, 12.0 hours, 24.0 hours),
Extraction forelimb median vein 2mL blood keeps sample；4) commercially available Beagle dog folic acid ELISA kit pair is used
The sample of each each sampling time point of tested treated animal carries out folate content detection, uses atomic absorption spectrphotometry
Method carries out Zn content detection to the sample of each each sampling time point of tested treated animal；And calculate each tested group 6
The average of each assessment item of Beagle dog, it need to be noted that be before sample analysis detects, this
Bright inventor has carried out system to the precision of detection method used, the response rate, specificity, detection limit etc.
Method validation, result shows, this analysis method is that science is feasible.
Use the result such as table 3 below of the Beagle dog bioavailability study that this test case carries out:
Table 3. embodiment 1, comparative example 1 and commercial preparation bioavailability study result
Comprehensive upper table 3 interpretation of result understands, and 1) embodiment 1 containing folic acid zinc gluconate of the present invention
Preparation, to the infiltration rate of folic acid and zinc gluconate faster, shows as Tmax=45 minute of folic acid, zinc
Tmax=1.5 hour；And comparative example 1 and commercially available YESUAN PIAN+zinc gluconate tablets, the Tmax=1.0 of folic acid
Hour, Tmax=2.0 hour of zinc.2) bioavailability of embodiment 1 gained folic acid zinc gluconate tablets
Apparently higher than comparative example 1 and commercial preparation, for zinc gluconate, embodiment 1 relative contrast's example 1
Say and improve (4157.0-3389.6)/3789.6=22.6%, the most commercially available YESUAN PIAN+zinc gluconate tablets
From the point of view of improve (4157.0-3315.3)/3315.3=25.4%.
It should be noted that the present inventor according further to the method in this test case to embodiment 2-6 system
The folic acid gluconic acid zinc preparation of standby gained has carried out bioavailability study, and result shows and embodiment 1
Equivalent or close situation.
Test case 4
The present inventor " added taste poly-essence diet therapy soup to few with reference to 2009 in what new Journal of Traditional Chinese Medicine was delivered
Essence, the experimentation of sperm quality impact in azoospermia rat epididymis " method described in a literary composition, to the present invention
Described prepare containing the health composition of folic acid zinc gluconate embodiment 1 gained preparation, comparative example 1 preparation
And commercially available YESUAN PIAN+zinc gluconate tablets studies, in addition to normal group and model group, all give for each tested group
Give folic acid and the zinc gluconate of 17.5mg/kg body weight of 0.1mg/kg body weight, result such as table 4 below institute
Show.
Table 4. embodiment 1, comparative example 1 and commercial preparation Ergonomy result of study
Note: 1. p ＜ 0.05 compared with normal group；2. p ＜ 0.05 compared with comparative example 1；With YESUAN PIAN+Portugal
Grape saccharic acid zinc metal sheet is than 3. p ＜ 0.05.
Comprehensive upper table 4 interpretation of result understands, embodiment 1 gained folic acid zinc gluconate tablets energy of the present invention
Enough significantly improving few essence, azoospermia, compare with commercial preparation with comparative example 1, embodiment 1 is close for sperm
The raising of degree, A level sperm and total motility rate all shows substantially, and has significant statistical significance.The present invention
The described preparation containing folic acid, zinc gluconate and sodium bicarbonate is due to the dissolution row of folic acid and zinc gluconate
For, the improvement of bioavailability, it is finally reflected being obviously improved for effect.
It should be noted that the present inventor according further to the method in this test case to embodiment 2-6 system
The folic acid gluconic acid zinc preparation of standby gained has carried out Ergonomy research, and result shows and is equal to embodiment 1
Or close situation.
Test case 5
The useful effect little in order to further illustrate gastrointestinal untoward reaction that health composition of the present invention brings
Really, this test case has carried out clinic to embodiment 1, comparative example 1 and commercially available YESUAN PIAN and zinc gluconate tablets
The comparative study of test-meal experiment.
Experimenter selects: selecting without smoking, the bad daily hobby such as drink, the health without gastrointestinal disease history becomes
Year male, the age 20-30 year between, 300 examples altogether, be randomly divided into three groups, often organize 100 examples.
Test-meal scheme: each group experimenter, test-meal same day, gives 0.4mg folic acid, 70mg gluconic acid on an empty stomach
The tested material of zinc dosage, continuous test-meal 14 days, record the gastrointestinal untoward reaction feelings after experimenter's test-meal every day
Condition.
Observation index: mainly to each group of tested patients with or without Nausea and vomiting, have a stomachache, phenomenon of suffering from abdominal pain is remembered
Record.
Table 5. embodiment 1, comparative example 1 and commercial preparation gastrointestinal untoward reaction result of study
Comprehensive upper table 5 interpretation of result understands, the health composition system containing folic acid zinc gluconate of the present invention
Standby embodiment 1 folic acid zinc gluconate tablets, compares with commercial preparation with comparative example 1, hence it is evident that reduce and be subject to
The adverse reaction rate of examination person, the income directly brought is that the clinical compliance of patient is improved, and this is right
From the point of view of needing the crowd of long-term supplemented with exogenous folic acid and zinc gluconate, it is highly beneficial.
It should be noted that embodiment 2-6 is prepared institute according further to the method in this test case by the present inventor
The folic acid gluconic acid zinc preparation obtained has carried out gastrointestinal untoward reaction research, and result shows and embodiment 1 etc.
Same or close situation.
The above is only the preferred embodiment of the present invention, it is noted that common for the art
For technical staff, on the premise of without departing from the technology of the present invention principle, it is also possible to make some improvement and change
Type, these improve and modification also should be regarded as protection scope of the present invention.
Claims (10)
1. the male health-care compositions containing folic acid zinc gluconate, it is characterised in that described health composition
Containing adjuvant acceptable on folic acid, zinc gluconate, sodium bicarbonate and galenic pharmacy, described folic acid, glucose
Acid zinc, the weight of sodium bicarbonate are 0.2-0.8: 35-70: 100-500.
The most according to claim 1, the male health-care compositions containing folic acid zinc gluconate, its feature exists
In, described folic acid, zinc gluconate, the weight of sodium bicarbonate are 0.4-0.8: 35-70: 200-300.
The most according to claim 1, the male health-care compositions containing folic acid zinc gluconate, its feature exists
In, on described galenic pharmacy, acceptable adjuvant includes filler, binding agent, disintegrating agent, lubricant, taste masking
Agent.
The most according to claim 1, the male health-care compositions containing folic acid zinc gluconate, its feature exists
In, described health composition can be prepared as being not limited to the oral solid formulation of tablet, capsule, powder.
Health composition containing folic acid zinc gluconate the most according to claim 4, it is characterised in that
Described oral solid formulation is tablet.
Male health-care compositions containing folic acid zinc gluconate the most according to claim 5, it is characterised in that
30 minutes dissolutions of described folic acid in tablets and zinc gluconate are not less than 85%.
Male health-care compositions containing folic acid zinc gluconate the most according to claim 5, it is characterised in that
45 minutes dissolutions of described folic acid in tablets and zinc gluconate are not less than 95%.
Male health-care compositions containing folic acid zinc gluconate the most according to claim 5, it is characterised in that
Described adjuvant is microcrystalline Cellulose, pregelatinized Starch and magnesium stearate, and the weight portion of described tablet consists of:
0.4 part of folic acid, zinc gluconate 70 parts, sodium bicarbonate 250 parts, microcrystalline Cellulose 60 parts, pregelatinated
Starch 40 parts, magnesium stearate 5 parts.
Male health-care compositions containing folic acid zinc gluconate the most according to claim 5, it is characterised in that
Described adjuvant is microcrystalline Cellulose, pregelatinized Starch and magnesium stearate, and the weight portion of described tablet consists of:
0.8 part of folic acid, zinc gluconate 70 parts, sodium bicarbonate 250 parts, microcrystalline Cellulose 60 parts, pregelatinated
Starch 40 parts, magnesium stearate 5 parts.
10. described in a claim 8 or 9, contain the preparation of the male health-care compositions of folic acid zinc gluconate
Method, it is characterised in that described tablet can be prepared from by following technique:
1) folic acid being crossed 120 mesh sieves, zinc gluconate crosses 80 mesh sieves, sodium bicarbonate, microcrystalline Cellulose,
Pregelatinized Starch, magnesium stearate cross 100 mesh sieves respectively；
2) weighing the folic acid of recipe quantity uses the equivalent method of progressively increasing to mix homogeneously with zinc gluconate, then with carbonic acid
Hydrogen sodium, microcrystalline Cellulose, pregelatinized Starch mix homogeneously；
3) by step 2) magnesium stearate of gained material and recipe quantity always mixes to uniformly, is pressed into through tablet machine
Sheet and get final product.
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