CN112245385A - Gel and gel patch for scrotum as well as preparation method and application of gel and gel patch - Google Patents
Gel and gel patch for scrotum as well as preparation method and application of gel and gel patch Download PDFInfo
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- CN112245385A CN112245385A CN202011335441.9A CN202011335441A CN112245385A CN 112245385 A CN112245385 A CN 112245385A CN 202011335441 A CN202011335441 A CN 202011335441A CN 112245385 A CN112245385 A CN 112245385A
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- Prior art keywords
- gel
- scrotum
- penetration enhancer
- patch
- per
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- 210000004706 scrotum Anatomy 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000011159 matrix material Substances 0.000 claims abstract description 22
- 239000004480 active ingredient Substances 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 18
- 239000003961 penetration enhancing agent Substances 0.000 claims abstract description 18
- 239000010410 layer Substances 0.000 claims abstract description 16
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims abstract description 14
- 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 claims abstract description 14
- 239000011670 zinc gluconate Substances 0.000 claims abstract description 14
- 229960000306 zinc gluconate Drugs 0.000 claims abstract description 14
- 235000011478 zinc gluconate Nutrition 0.000 claims abstract description 14
- 206010003883 azoospermia Diseases 0.000 claims abstract description 10
- 208000008634 oligospermia Diseases 0.000 claims abstract description 10
- 230000036616 oligospermia Effects 0.000 claims abstract description 10
- 231100000528 oligospermia Toxicity 0.000 claims abstract description 10
- 206010067162 Asthenospermia Diseases 0.000 claims abstract description 8
- 239000011241 protective layer Substances 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 239000002202 Polyethylene glycol Substances 0.000 claims description 18
- 229920001223 polyethylene glycol Polymers 0.000 claims description 18
- 238000002156 mixing Methods 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 12
- 239000003755 preservative agent Substances 0.000 claims description 10
- 230000002335 preservative effect Effects 0.000 claims description 10
- 239000000230 xanthan gum Substances 0.000 claims description 8
- 229920001285 xanthan gum Polymers 0.000 claims description 8
- 229940082509 xanthan gum Drugs 0.000 claims description 8
- 235000010493 xanthan gum Nutrition 0.000 claims description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 7
- 239000004202 carbamide Substances 0.000 claims description 7
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 230000003078 antioxidant effect Effects 0.000 claims description 6
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 claims description 5
- 239000003906 humectant Substances 0.000 claims description 5
- 235000013923 monosodium glutamate Nutrition 0.000 claims description 5
- 229940073490 sodium glutamate Drugs 0.000 claims description 5
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 4
- 239000006185 dispersion Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 3
- 229920002125 Sokalan® Polymers 0.000 claims description 3
- 229960001631 carbomer Drugs 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000003002 pH adjusting agent Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000003020 moisturizing effect Effects 0.000 claims 1
- 238000010579 first pass effect Methods 0.000 abstract description 3
- 238000013461 design Methods 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 64
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical group [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 18
- 239000000243 solution Substances 0.000 description 15
- 239000012153 distilled water Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 11
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical group OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 9
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 9
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 9
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 9
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical group CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 9
- 235000010265 sodium sulphite Nutrition 0.000 description 9
- 229960004063 propylene glycol Drugs 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 238000000465 moulding Methods 0.000 description 5
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 229940068968 polysorbate 80 Drugs 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 229950008882 polysorbate Drugs 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 230000019100 sperm motility Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 210000000918 epididymis Anatomy 0.000 description 3
- 201000010063 epididymitis Diseases 0.000 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- 229940001482 sodium sulfite Drugs 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 229960004418 trolamine Drugs 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- NIOHNDKHQHVLKA-UHFFFAOYSA-N acetic acid;7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde Chemical compound CC(O)=O.CC(C)C1=C(O)C(O)=C(C=O)C2=C(O)C(C=3C(O)=C4C(C=O)=C(O)C(O)=C(C4=CC=3C)C(C)C)=C(C)C=C21 NIOHNDKHQHVLKA-UHFFFAOYSA-N 0.000 description 2
- 229940049638 carbomer homopolymer type c Drugs 0.000 description 2
- 229940043234 carbomer-940 Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 239000004745 nonwoven fabric Substances 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 235000021313 oleic acid Nutrition 0.000 description 2
- 239000005871 repellent Substances 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 206010067484 Adverse reaction 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000037374 absorbed through the skin Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- 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
- A61K31/28—Compounds containing heavy metals
- A61K31/315—Zinc compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gynecology & Obstetrics (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a gel and a gel patch for scrotum as well as a preparation method and application thereof, and solves the problem of low bioavailability of oral administration in the prior art. Every 100mL of the gel for scrotum comprises 0.5-2g of gel matrix, 0.5-1.1g of active ingredient, 3-8mL of penetration enhancer or 3-8g of penetration enhancer; wherein the active ingredients comprise the following substances in percentage by weight: 500-1500 parts of L-carnitine and 50-100 parts of zinc gluconate. The gel patch for the scrotum comprises a back lining layer, a gel layer and a protective layer. The invention relates to application of gel and gel patch for scrotum in preparing medicine for treating oligospermia and/or asthenospermia. The invention has scientific design and reasonable formula, creatively adopts the mode of externally applying gel for treating oligospermia or/and asthenospermia, effectively avoids the first pass effect of the medicine and improves the bioavailability.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a gel for scrotum, a gel patch, and a preparation method and application thereof.
Background
Oligospermia refers to a condition in which the number of sperm in the semen of a male with fertility is lower than normal. The international health organization stipulates that the sperm per ml of the male is not less than 15 multiplied by 109If it is less than 15X 109The disease is classified as oligospermia, and the fertility is greatly influenced. Asthenospermia (astenospermia) refers to a condition in which less than 32% of the sperm in the sperm parameters are moving forward (grade a and b), also known as asthenospermia. In recent years, the incidence of oligospermia in men has been increasing year by year.
In the prior art, the treatment of male oligospermia is mainly to improve the sperm semen quality by supplementing medicines, nutrients, traditional Chinese medicines and the like through oral administration or veins. After oral administration, the medicine is transformed by liver and metabolized systemically, and has low local concentration in testis, limited action and poor effect.
Therefore, providing a pharmaceutical preparation with definite therapeutic effect and avoiding the first-pass effect is a problem to be solved by those skilled in the art.
Disclosure of Invention
The invention aims to provide a gel for scrotum, which is applied to the skin of the scrotum and is absorbed through the skin to treat oligospermia and/or asthenospermia.
Another object of the present invention is to provide a gel patch containing the gel.
The invention also aims to provide a preparation method of the gel.
The fourth object of the present invention is to provide the use of the gel and the gel patch.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
every 100mL of the gel for the scrotum comprises 0.5-2g of gel matrix, 0.5-1.1g of active ingredient, 3-8mL of penetration enhancer or 3-8g of penetration enhancer; wherein the active ingredients comprise the following substances in percentage by weight: 500-1500 parts of L-carnitine and 50-100 parts of zinc gluconate.
In some embodiments of the invention, each 100mL of gel comprises 2g of gel matrix, 1.1g of active ingredient, 4.5mL of penetration enhancer or 4.5g of penetration enhancer.
In some embodiments of the invention, the active ingredient comprises the following materials by weight: 1000 parts of L-carnitine and 70 parts of zinc gluconate.
In some embodiments of the present invention, a humectant, or/and an antioxidant, or/and a solubilizer, or/and a preservative, or/and a pH regulator is further included.
In some embodiments of the invention, the humectant is 2-15mL, more preferably 2.5mL, per 100mL of gel; preferably, the antioxidant is present in an amount of 0.1 to 0.4g, more preferably 0.2g, per 100mL of gel.
In some embodiments of the invention, the solubilizer is present in an amount of 0.3 to 0.8g, more preferably 0.5g, per 100mL of gel;
preferably, the amount of preservative is 0.05-0.2g, more preferably 0.1g, per 100mL of gel;
preferably, the pH adjusting agent is 1-2g, more preferably 1.5g, per 100mL of gel.
In some embodiments of the invention, the gel matrix comprises any one or more of carbomer, xanthan gum and cellulose derivatives;
or/and the penetration enhancer is one or more of propylene glycol, urea, azone or sodium glutamate.
The humectant, the antioxidant, the solubilizer, the preservative and the pH regulator are all the prior art. In some embodiments of the invention, propylene glycol is the humectant and the penetration enhancer for L-carnitine, preferably in an amount of 2.5mL/100mL of gel.
In some embodiments of the invention, the sodium glutamate is a penetration enhancer for zinc gluconate; the amount is preferably 2g/100mL of gelling agent.
In some embodiments of the invention, the antioxidant is sodium sulfite, the solubilizer is polysorbate 80, the preservative is ethylparaben, and the pH regulator is triethanolamine. The gel patch for the scrotum comprises a back lining layer, a gel layer coated on the back lining layer and a protective layer covered on the gel layer, wherein the gel layer is the gel for the scrotum.
In some embodiments of the present invention, the gel layer in the gel patch for scrotum has a thickness of 0.8 to 1.5mm, preferably 1 mm.
In the present invention, the back layer and the protective layer of the gel patch for scrotum are both the prior art. The lining layer is preferably water-repellent breathable non-woven fabric; the protective layer is preferably a PE film.
The preparation method of the gel for scrotum is characterized by comprising the following steps:
step 1, adding water into a gel matrix to fully swell the gel matrix for later use; step 2, taking the active ingredient and the preservative, adding a solvent for dispersion, then adding the rest auxiliary materials, uniformly mixing, then adding the mixture into the swollen gel matrix, and uniformly mixing to obtain the gel; or adding into swollen gel matrix, mixing, and adding water to desired amount;
preferably, when the penetration enhancer is urea, the penetration enhancer is added into the dispersion liquid in which the active ingredients and the preservative are dispersed after being dissolved by adding water; in the step 2, the solvent is polyethylene glycol; the dosage of the solvent is 40-60mL, preferably 50mL, per 100mL of the gel.
The invention relates to application of a gel for scrotum or a gel patch for scrotum in preparing a medicament for treating oligospermia and/or asthenospermia. When the gel is used, the gel is externally applied to scrotum skin and is coated for 1 to 2 times every day; the thickness of each coating is about 1mm
When the gel patch for scrotum is used, the protective layer is removed, and the gel patch is applied to the skin of scrotum 1-2 times daily for 6 hr each time.
Compared with the prior art, the invention has the following beneficial effects:
the invention has scientific design and reasonable formula, creatively adopts the mode of externally applying gel for treating oligospermia or/and asthenospermia, effectively avoids the first pass effect of the medicine and improves the bioavailability.
The gel and the gel patch can reduce the total dosage of the medicine and the adverse reaction of the medicine by the transdermal administration of the scrotum, meet the concept of external treatment of internal diseases, and have the advantages of convenient and comfortable use, good biocompatibility and the like.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1
The embodiment discloses a preparation method of a gel for scrotum, which comprises the following raw material formula:
2g of sodium carboxymethylcellulose, 1000mg of L-carnitine, 70mg of zinc gluconate, 1.5g of triethanolamine, 2.5mL of propylene glycol, 50mL of polyethylene glycol, 800.5g of polysorbate, 0.2g of sodium sulfite, 0.1g of ethylparaben, 2g of sodium glutamate and 100mL of distilled water.
The preparation method comprises the following steps:
adding appropriate amount of distilled water into sodium carboxymethylcellulose, stirring, and swelling to obtain matrix solution;
dissolving L-carnitine and zinc gluconate with polyethylene glycol to obtain polyethylene glycol solution; adding triethanolamine, propylene glycol, polysorbate 80, sodium sulfite, ethylparaben and sodium glutamate into polyethylene glycol, mixing well, adding into swelled sodium hydroxymethyl cellulose matrix solution, mixing well, and adding distilled water to make 100 mL.
Example 2
The embodiment discloses a preparation method of a gel for scrotum, which comprises the following raw material formula:
0.5g of xanthan gum, 500mg of L-carnitine, 50mg of zinc gluconate, 1.5g of triethanolamine, 15mL of propylene glycol, 60mL of polyethylene glycol, 800.3g of polysorbate, 0.2g of sodium sulfite, 0.1g of ethylparaben, 3g of urea and 100mL of distilled water.
The preparation method comprises the following steps:
adding a proper amount of distilled water into xanthan gum, stirring, and fully swelling to obtain a matrix liquid for later use;
dissolving urea in appropriate amount of distilled water;
dissolving L-carnitine and zinc gluconate with polyethylene glycol to obtain polyethylene glycol solution; adding triethanolamine, propylene glycol, polysorbate 80, sodium sulfite and ethylparaben into polyethylene glycol, mixing well, adding into swollen xanthan gum matrix solution, adding urea solution, mixing well, and adding distilled water to prepare 100 mL.
Example 3
The embodiment discloses a preparation method of a gel for scrotum, which comprises the following raw material formula:
2g of sodium carboxymethylcellulose, 1500mg of L-carnitine, 100mg of zinc gluconate, 2g of triethanolamine, 7mL of propylene glycol, 30mL of polyethylene glycol, 800.8g of polysorbate, 0.4g of sodium sulfite, 0.2g of ethylparaben, 2mL of oleic acid and 100mL of distilled water.
The preparation method comprises the following steps:
adding appropriate amount of distilled water into sodium carboxymethylcellulose, stirring, and swelling to obtain matrix solution;
dissolving L-carnitine and zinc gluconate with polyethylene glycol to obtain polyethylene glycol solution; adding triethanolamine, propylene glycol, polysorbate 80, sodium sulfite, ethylparaben and oleic acid into polyethylene glycol solution, mixing well, adding into swelled sodium carboxymethylcellulose matrix solution, mixing well, and adding distilled water to prepare 100 mL.
Example 4
The embodiment discloses a preparation method of a gel for scrotum, which comprises the following raw material formula:
9400.8g of carbomer, 0.5g of xanthan gum, 1000mg of L-carnitine, 70mg of zinc gluconate, 1.5g of triethanolamine, 10mL of glycerol, 50mL of polyethylene glycol, 800.5g of polysorbate, 0.2g of sodium sulfite, 0.1g of ethylparaben, 5mL of azone and 100mL of distilled water.
The preparation method comprises the following steps:
putting carbomer 940 and xanthan gum into the same container, adding a proper amount of distilled water, and stirring to fully swell carbomer 940 and xanthan gum to obtain matrix liquid for later use;
dissolving L-carnitine and zinc gluconate with polyethylene glycol to obtain polyethylene glycol solution; adding triethanolamine, glycerol, polysorbate 80, sodium sulfite, ethylparaben and azone into polyethylene glycol solution, mixing, adding into matrix solution, mixing, and adding distilled water to obtain 100 mL.
Example 5
The embodiment of the invention discloses a preparation method of a gel patch for scrotum, which comprises the following steps: uniformly coating the gel prepared in the embodiment 1 with the thickness of about 0.8-1.5mm on one surface of a water-repellent breathable non-woven fabric, covering a PE film on the gel layer after coating, and cutting into a specified size to obtain the gel patch for the scrotum.
Example 6
This example discloses a pharmacodynamic examination of the gels of the invention.
Animal grouping and administration
Experimental animals and groups: clean grade SD rats, male, 13 weeks old, body weight 180-. The test samples were randomly divided into a blank control group, a model group, a test sample low dose group, a test sample medium dose group and a test sample high dose group, and 13 animals per group.
Test drugs:
dosage group administration in the test article: the gel prepared in example 1 was used;
the low dose group of the test article is used as follows: compared with the gel prepared in example 1, the content of each active ingredient is 1/2 of example 1, and the rest conditions are consistent;
high-dose group medication of test samples: compared with the gel prepared in example 1, the content of each active ingredient is 2 times of that of example 1, and the rest conditions are consistent;
the model group is used for medicine: compared with the gel prepared in the example 1, the gel does not contain active ingredients, and the other conditions are consistent;
blank control group medication: compared with the gel prepared in example 1, the gel does not contain active ingredients, and the rest conditions are consistent.
The molding medicine comprises the following components: adding edible oil into gossypol acetate to prepare 50mg/mL suspension.
Molding: and (3) irrigating the rats in the model group, the test sample low-dose group, the test sample medium-dose group and the test sample high-dose group 15 days before the experiment with gossypol acetate suspension, wherein the irrigation dose is 5mg/kg of the weight of the rats, and the administration is carried out for 1 time and 5 times continuously in 3 days.
On day 16, 3 rats were randomly selected from each group, sacrificed, examined for visceral index, epididymis collected, and examined for sperm count and sperm survival rate. Compared with the blank control group, the sperm motility rate and the sperm quantity of the other groups are obviously reduced, and the molding is successful.
After the molding is successful, the rest animals are respectively coated with corresponding medicines on the scrotum skin, the coating thickness is about 1mm, and the application is carried out once a day for 15 days continuously. Fixing animal, applying medicine for 6 hr, and allowing the animal to move freely to avoid loss of medicine; . On day 16 of the experiment, the rats were weighed and sacrificed.
In this example, the sperm count method was: after a male rat is sacrificed, the abdominal cavity is cut, the epididymis is taken out and washed clean by normal saline, then the epididymis is put into a culture dish containing 3mL of PBS buffer solution and is cut into small pieces, a suction pipe blows the suspension gently for 5-6 times, and the suspension is kept stand for 3-5 min to prepare the suspension. Taking the sperm suspension, dripping one drop into an erythrocyte counting plate, counting the number of sperms in 5 middle squares under a 40-time optical microscope, repeatedly counting for 3 times, and taking the average value as the final result.
Determination of vital essence rate: the sperm suspension was dropped onto a glass slide, and a drop of eosin was mixed with the drop and covered with the slide. Immediately observing the number of sperms in 5 visual fields, wherein the live sperms under the microscope are colorless, the dead sperms are red, accurately recording and calculating the live sperm rate.
Viable sperm ratio (%). live sperm/(viable sperm + dead sperm) × 100%
Measurement of sperm motility: taking a drop of suspension on a clean glass slide, covering the glass slide on the clean glass slide, counting 5 visual field sperm counts under a high power lens, respectively recording the sperm counts at all levels, and calculating the sperm motility.
The criteria are as follows: (0) (ii) inactive; not moving forwards or rotating in place; (II) slow forward or rotational forward; (III) enabling the medium-speed straight line to move forward; (IV) moving forwards rapidly and linearly.
Activity (%) - (I + II + III + IV)/(0 + I + II + III + IV). times.100%
The results are shown in the following table:
TABLE 1
Note: comparison with blank control: p < 0.05X P < 0.01
As can be seen from Table 1, molding was successful.
TABLE 2
Note: comparison with blank control: p < 0.05, P < 0.01; in comparison with the set of models,#P＜0.05，##P＜0.01。
the results show that the middle and high dose groups of the gel can improve the number of sperms of rats, the sperm motility rate and the motility.
The embodiments described above are some, but not all embodiments of the invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the invention as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Claims (10)
1. A gel for scrotum is characterized in that each 100mL of gel comprises 0.5-2g of gel matrix, 0.5-1.1g of active ingredient, 3-8mL of penetration enhancer or 3-8g of penetration enhancer; wherein the active ingredients comprise the following substances in percentage by weight: 500-1500 parts of L-carnitine and 50-100 parts of zinc gluconate.
2. The gel for scrotum according to claim 1, wherein each 100mL of the gel comprises 2g of gel matrix, 1.1g of active ingredient, 4.5mL of penetration enhancer or 4.5g of penetration enhancer.
3. The scrotal gel according to claim 1 or 2, wherein said active ingredient comprises the following substances in weight ratio: 1000 parts of L-carnitine and 70 parts of zinc gluconate.
4. The gel for scrotum according to claim 1, further comprising a humectant, or/and an antioxidant, or/and a solubilizer, or/and a preservative, or/and a pH regulator.
5. The gel for scrotum according to claim 4 wherein the amount of the moisturizing agent is 2 to 15mL, more preferably 2.5mL, per 100mL of the gel;
preferably, the antioxidant is present in an amount of 0.1 to 0.4g, more preferably 0.2g, per 100mL of gel.
6. The gel for scrotum according to claim 4 wherein the amount of solubilizer is 0.3 to 0.8g, more preferably 0.5g, per 100mL of gel;
preferably, the amount of preservative is 0.05-0.2g, more preferably 0.1g, per 100mL of gel;
preferably, the pH adjusting agent is 1-2g, more preferably 1.5g, per 100mL of gel.
7. The gel for the scrotum according to claim 1, wherein said gel base comprises any one or more of cellulose derivatives, carbomer, xanthan gum;
or/and the penetration enhancer is one or more of propylene glycol, urea, azone and sodium glutamate.
8. A gel patch for the scrotum, comprising a backing layer, a gel layer applied to the backing layer, and a protective layer covering the gel layer, wherein the gel layer is the gel for the scrotum according to any one of claims 1 to 7.
9. The method for preparing a gel for scrotum according to any one of claims 1 to 7, comprising the steps of:
step 1, adding water into a gel matrix to fully swell the gel matrix for later use;
step 2, taking the active ingredient and the preservative, adding a solvent for dispersion, then adding the rest auxiliary materials, uniformly mixing, then adding the mixture into the swollen gel matrix, and uniformly mixing to obtain the gel; or adding into swollen gel matrix, mixing, and adding water to desired amount;
preferably, when the penetration enhancer is urea, the penetration enhancer is added into the dispersion liquid in which the active ingredients and the preservative are dispersed after being dissolved by adding water;
preferably, in the step 2, the solvent is polyethylene glycol; the dosage of the solvent is 40-60mL, preferably 50mL, per 100mL of the gel.
10. Use of the gel for scrotum of any one of claims 1 to 7 or the gel patch for scrotum of claim 8 for the preparation of a medicament for the treatment of oligospermia or/and asthenospermia.
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| CN101953844A (en) * | 2010-02-28 | 2011-01-26 | 黄胜先 | Medicament for improving sperm quality and treating male sterility |
| CN102018655A (en) * | 2009-09-17 | 2011-04-20 | 中国科学院理化技术研究所 | Transdermal drug delivery combined preparation |
| CN102697755A (en) * | 2012-06-15 | 2012-10-03 | 华东理工大学 | Novel levo-carnitine hydrogel patch and preparation method thereof |
| CN110302358A (en) * | 2019-08-07 | 2019-10-08 | 广州昊森医药科技发展有限公司 | Improve the composition of human sperm's activity and quality |
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2020
- 2020-11-24 CN CN202011335441.9A patent/CN112245385A/en active Pending
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| CN102018655A (en) * | 2009-09-17 | 2011-04-20 | 中国科学院理化技术研究所 | Transdermal drug delivery combined preparation |
| CN101953844A (en) * | 2010-02-28 | 2011-01-26 | 黄胜先 | Medicament for improving sperm quality and treating male sterility |
| CN102697755A (en) * | 2012-06-15 | 2012-10-03 | 华东理工大学 | Novel levo-carnitine hydrogel patch and preparation method thereof |
| CN110302358A (en) * | 2019-08-07 | 2019-10-08 | 广州昊森医药科技发展有限公司 | Improve the composition of human sperm's activity and quality |
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