CN106943340A - 一种盐酸利多卡因凝胶 - Google Patents
一种盐酸利多卡因凝胶 Download PDFInfo
- Publication number
- CN106943340A CN106943340A CN201710294277.3A CN201710294277A CN106943340A CN 106943340 A CN106943340 A CN 106943340A CN 201710294277 A CN201710294277 A CN 201710294277A CN 106943340 A CN106943340 A CN 106943340A
- Authority
- CN
- China
- Prior art keywords
- lidocaine hydrochloride
- jelly
- chitosan
- malic acid
- content
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229960004393 lidocaine hydrochloride Drugs 0.000 title claims abstract description 29
- 235000015110 jellies Nutrition 0.000 title claims abstract description 16
- 239000008274 jelly Substances 0.000 title claims abstract description 16
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims abstract description 15
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000001630 malic acid Substances 0.000 claims abstract description 15
- 235000011090 malic acid Nutrition 0.000 claims abstract description 15
- 229920001661 Chitosan Polymers 0.000 claims abstract description 14
- 239000000499 gel Substances 0.000 claims abstract description 11
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 239000011975 tartaric acid Substances 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- 210000003928 nasal cavity Anatomy 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 5
- 229920002125 Sokalan® Polymers 0.000 description 5
- 229960001631 carbomer Drugs 0.000 description 5
- 210000004081 cilia Anatomy 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 229960005015 local anesthetics Drugs 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 210000002850 nasal mucosa Anatomy 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 235000005979 Citrus limon Nutrition 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000002460 anti-migrenic effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000001331 nose Anatomy 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- UYVVLXVBEQAATF-UHFFFAOYSA-N 4-(1,3,7,12-tetrahydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl)pentanoic acid Chemical compound OC1CC2CC(O)CC(O)C2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 UYVVLXVBEQAATF-UHFFFAOYSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 244000248349 Citrus limon Species 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- 235000011054 acetic acid Nutrition 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 231100000435 percutaneous penetration Toxicity 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000004544 sputter deposition Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 238000002210 supercritical carbon dioxide drying Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000002268 wool Anatomy 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
-
- 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
- A61K9/0043—Nose
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
一种盐酸利多卡因凝胶，其特征是所述凝胶由以下重量百分比的组分组成：作为活性成分的盐酸利多卡因一水合物2～5％,壳聚糖1.5％‑2％，卡波姆940 0.3～0.5％，磷脂酰胆碱0.5‑1％，苹果酸0.2～0.4％，以及余量的水。
Description
技术领域
本发明涉及一种盐酸利多卡因凝胶。
背景技术
盐酸利多卡因属于酰胺类的局麻药，由于其具有作用快而强，时效长，穿透力大、价格低廉等优点，被认为是理想的局麻药。由于口服给药的生物利用度较低，多采用注射或局部给药方式，现有的盐酸利多卡因凝胶剂为2％浓度(以盐酸利多卡因一水合物计，CAS：6108-05-0Lidocaine Hydrochloride，LID)，可以作为局麻药应用于经尿道施行检查和治疗需局部麻醉者。但随着对盐酸利多卡因研究的伸入，人们发现其除了作为局麻药外还可以有多种用途，如可以鼻腔给药的形式用于治疗偏头痛，但由于盐酸利多卡因本身酸性较强，现有的盐酸利多卡因凝胶剂在用于前述用途时，存在着提供药物在鼻腔内保持时间短、起效较慢，以及药效持续时间短的缺陷，影响了盐酸利多卡因的应用。基于此，提供一种能够能够快速起效，并实现持续长时间稳定释药的氟比洛芬巴布剂成为现有技术中亟待解决的问题。
发明内容
为解决前述技术问题，本发明提供了一种盐酸利多卡因凝胶，其特征是所述凝胶由以下重量百分比的组分组成：作为活性成分的盐酸利多卡因一水合物2～5％,壳聚糖1.5％-2％，卡波姆940 0.3～0.5％，磷脂酰胆碱0.5-1％，苹果酸0.2～0.4％，以及余量的水。
所述的盐酸利多卡因凝胶，其特征在于所述的盐酸利多卡因一水合物含量为3～5％。
所述的盐酸利多卡因凝胶，其特征在于所述的壳聚糖含量为2％，卡波姆含量为0.3％。
所述的盐酸利多卡因凝胶以如下方法配制：
1)将盐酸利多卡因溶于少量水中，并加入处方量的磷脂酰胆碱溶解，
2)将苹果酸配制成为重量百分比浓度为1～3％的溶液，再将壳聚糖、卡波姆940加入苹果酸溶液中充分溶胀，然后将步骤1)得到的溶液缓慢加入并搅拌均匀。
在研究中发现，在凝胶基质的主要胶凝剂选用壳聚糖的基础上，通过优选辅料配方，加入卡波姆、磷脂酰胆碱和苹果酸，可以显著提高盐酸利多卡因凝胶的性能。能够在选用较高盐酸利多卡因浓度的基础上使其，既可以快速起效，又能够保持较为稳定药物释放速度。此外我们意外的发现，与常规的用于溶胀壳聚糖的乙酸相比，在处方中加入苹果酸可以显著的提高得到的凝胶在进行鼻腔给药时的起效速度，使其在用于鼻腔给药治疗偏头痛等用途时能够产生更好的治疗效果，本发明提供的凝胶处方中，采用了壳聚糖和卡波姆作为胶凝剂，可并加入了少量的磷脂酰胆碱，在实验中我们意外的发现，一定比例的壳聚糖和卡波姆配比后得到凝胶，不但胶体形态较好，而且在进行给药时实现较快的药物溶出速度，而加入磷脂酰胆碱和苹果酸除了能够进一步提高溶出速度以外，也能显著改善药物的释放曲线，尤其是当盐酸利多卡因含量较高时，可以实现持续稳定的释药。在处方筛选阶段，我们将乙酸替换为乳酸、酒石酸、苹果酸等多种常用的有机酸，意外的发现仅有当选用苹果酸时得到的凝胶在进行鼻腔给药时，能够显著降低凝胶的纤毛毒性，使其能够用于日常偏头痛等疾病的治疗。
具体实施方式
本发明实施例中的盐酸利多卡因凝胶以如下方法配制：
1)将盐酸利多卡因溶于少量水中，并加入处方量的磷脂酰胆碱溶解，
2)将苹果酸配制成为重量百分比浓度为1～3％的溶液，再将壳聚糖、卡波姆940加入苹果酸溶液中充分溶胀，然后将步骤1)得到的溶液缓慢加入并搅拌均匀。
所有实施例及对照例中，壳聚糖的脱乙酰度≥90％。
实施例1～3的配方见下表
对照例1～3中，胶凝剂仅为4％壳聚糖或0.5％卡波姆，配方见下表
对照例4～6中，分别不加入磷脂酰胆碱及将苹果酸替换为乙酸、乳酸、酒石酸、柠檬酸，配方见下表
药理实施例1，体外透皮实验
采用改良Franz扩散池法，以离体3月龄大鼠腹部皮肤为屏障，用实施例1～3及对照例1～6制备得到的巴布贴剂进行进行体外透皮试验。具体实验方法为：
取3月龄健康大鼠麻醉处死后，用剪刀除尽腹部毛，取下无损伤的皮肤，除去皮下组织，洗净后分别固定于Franz扩散池的释放口，接受室中加入pH7.4磷酸缓冲液作释放介质，保持内皮层与溶液密切接触。将揭去保护层的巴布剂贴于皮肤上，调节水浴使外层套层温度恒定于(32±0.5)℃，搅拌速度为100rpm，分别于0、1h、2h、4h、6h、8h、12h小时吸取释放介质4ml，同时补加等量PBS液。计算累计吸收百分数(即累计透过的盐酸利多卡因占药物储库中盐酸利多卡因总量的百分比分数)结果如下表
上述结果表明，本发明提供的凝胶剂，在进行体外透皮吸收实验时，12h的累计药物透过率均高于90％，且药物释放率随时间增加速度较为均匀、，且在进一步实验中我们还发现，该辅料配方与盐酸利多卡因有关联性，当改变活性成分时，即使采用同样的辅料配方，也会无法产生本发明实施例制剂中的快速均匀释药效果。此外，通过实施例与对照例的对比可以看出本发明提供的凝胶剂其释药性能明显高于对照例，说明本发明提供的凝胶基质配方通过优选辅料可以提高盐酸利多卡因的释药性能。
药理实施例1，鼻粘膜毒性试验
以大鼠为实验动物。选取SD大鼠30只，随机分成9个实验组、1个阳性对照组和1个阴性对照组，，每组5只，实验组1～9的给药分组情况同药理实施例2，阳性对照组采用1％去氧胆酸钠溶液。阴性对照组采用生理盐水。
给药方法：单侧鼻腔每天给药一次，每次50μL。分别连续给药7天，在最后一次给药后的24h处死大鼠。剪开鼻腔，肉眼观察有无充血及水肿现象。其中，每组各取大鼠鼻1只，取给药侧鼻中隔粘膜，用生理盐水洗净血块及粘液，用2.5％戊二醛和1％锇酸双重固定，梯度浓度乙醇脱水，CO2临界点干燥，离子溅射仪喷金，制备电镜标本进行扫描电镜观察。
采用实施例1～3药物的实验组1～3及采用对照例1～3的实验组4～6大鼠给药1周后，肉眼观察鼻腔粘膜，均无充血和水肿现象；扫描电镜观察结果表明，大鼠鼻粘膜表面纤毛浓密，排列有序，无脱落和倒伏现象，与生理盐水对照组无显著差异。阳性对照组大鼠鼻粘膜表面纤毛脱落严重，纤毛萎缩并成簇状分散，而对照组4～9大鼠鼻黏膜损伤轻微，上皮表面纤毛分布稠密，纤毛排列不规则，有倒伏现象，说明当同时加入磷脂酰胆碱和苹果酸可以克服现有的辅料产生的鼻粘膜毒性。
Claims (4)
1.一种盐酸利多卡因凝胶，其特征是所述凝胶由以下重量百分比的组分组成：作为活性成分的盐酸利多卡因一水合物2～5％,壳聚糖1.5％-2％，卡波姆940 0.3～0.5％，磷脂酰胆碱0.5-1％，苹果酸0.2～0.4％，以及余量的水。
2.如权利要求1所述的盐酸利多卡因凝胶，其特征在于所述的盐酸利多卡因一水合物含量为3～5％。
3.如权利要求1或2所述的盐酸利多卡因凝胶，其特征在于所述的壳聚糖含量为2％，卡波姆含量为0.3％。
4.如权利要求1所述的盐酸利多卡因凝胶，其特征在于以如下方法配制：
1)将盐酸利多卡因溶于少量水中，并加入处方量的磷脂酰胆碱溶解，
2)将苹果酸配制成为重量百分比浓度为1～3％的溶液，再将壳聚糖、卡波姆940加入苹果酸溶液中充分溶胀，然后将步骤1)得到的溶液缓慢加入并搅拌均匀。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710294277.3A CN106943340A (zh) | 2017-04-28 | 2017-04-28 | 一种盐酸利多卡因凝胶 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710294277.3A CN106943340A (zh) | 2017-04-28 | 2017-04-28 | 一种盐酸利多卡因凝胶 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106943340A true CN106943340A (zh) | 2017-07-14 |
Family
ID=59477904
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710294277.3A Withdrawn CN106943340A (zh) | 2017-04-28 | 2017-04-28 | 一种盐酸利多卡因凝胶 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106943340A (zh) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107789621A (zh) * | 2017-12-15 | 2018-03-13 | 阜阳市平衡医疗保健器械有限公司 | 一种治疗头痛的药物及其配制方法 |
| CN111840553A (zh) * | 2019-04-15 | 2020-10-30 | 湖州依诺唯新药物制剂有限公司 | 脂性药物制剂及其应用 |
| CN113398101A (zh) * | 2021-07-30 | 2021-09-17 | 温州医科大学附属眼视光医院 | 一种复方利多卡因凝胶贴剂 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5958443A (en) * | 1991-10-30 | 1999-09-28 | Mdv Technologies, Inc. | Medical uses of in situ formed gels |
| CN102018696A (zh) * | 2010-11-22 | 2011-04-20 | 北京泰德制药股份有限公司 | 一种含有利多卡因或其药用盐的皮肤外用制剂 |
| CN102379862A (zh) * | 2011-11-03 | 2012-03-21 | 北京泰德制药股份有限公司 | 一种含有水杨酸羟乙酯的亲水性巴布剂 |
| CN105407718A (zh) * | 2013-06-04 | 2016-03-16 | 维奥姆生物科学有限公司 | 涂布的颗粒和包括其的组合物 |
| CN105903068A (zh) * | 2016-06-02 | 2016-08-31 | 四川奎星医用高分子制品有限责任公司 | 含有镇痛药物的医用复合壳聚糖凝胶 |
-
2017
- 2017-04-28 CN CN201710294277.3A patent/CN106943340A/zh not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5958443A (en) * | 1991-10-30 | 1999-09-28 | Mdv Technologies, Inc. | Medical uses of in situ formed gels |
| CN102018696A (zh) * | 2010-11-22 | 2011-04-20 | 北京泰德制药股份有限公司 | 一种含有利多卡因或其药用盐的皮肤外用制剂 |
| CN102379862A (zh) * | 2011-11-03 | 2012-03-21 | 北京泰德制药股份有限公司 | 一种含有水杨酸羟乙酯的亲水性巴布剂 |
| CN105407718A (zh) * | 2013-06-04 | 2016-03-16 | 维奥姆生物科学有限公司 | 涂布的颗粒和包括其的组合物 |
| CN105903068A (zh) * | 2016-06-02 | 2016-08-31 | 四川奎星医用高分子制品有限责任公司 | 含有镇痛药物的医用复合壳聚糖凝胶 |
Non-Patent Citations (2)
| Title |
|---|
| 吕玥，等: "以壳聚糖为基质的盐酸利多卡因凝胶剂的研究", 《天津药学》 * |
| 张珩，等: "盐酸利多卡因凝胶剂的制备工艺研究", 《西北药学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107789621A (zh) * | 2017-12-15 | 2018-03-13 | 阜阳市平衡医疗保健器械有限公司 | 一种治疗头痛的药物及其配制方法 |
| CN111840553A (zh) * | 2019-04-15 | 2020-10-30 | 湖州依诺唯新药物制剂有限公司 | 脂性药物制剂及其应用 |
| CN113398101A (zh) * | 2021-07-30 | 2021-09-17 | 温州医科大学附属眼视光医院 | 一种复方利多卡因凝胶贴剂 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8431140B2 (en) | Topical compositions | |
| US12059469B2 (en) | Compositions and methods for wound treatment | |
| RS59211B2 (sr) | Antifungalni topikalni sastav i postupci tretmana | |
| CN106943340A (zh) | 一种盐酸利多卡因凝胶 | |
| DE102009003942A1 (de) | Verwendung von Deuteriumoxid zur Behandlung Virus-basierter Erkrankungen des Auges | |
| EP2110132B1 (de) | Verwendung von Deuteriumoxid als Elastase-Inhibitor | |
| US10517835B2 (en) | Composition and methods of treatment | |
| EP2079527B1 (de) | Verwendung von Deuteriumdioxid zur Behandlung von nicht-malignen hyperproliferativen Erkrankungen der Haut | |
| CN118490615A (zh) | 含有脱氧胆酸的可溶性微针贴片及其制备方法和应用 | |
| CN102731630B (zh) | 一种具有透皮能力的抗氧化短肽 | |
| US10099995B2 (en) | Resveratrol esters | |
| CN117100681A (zh) | 离子液体与海绵骨针的促渗组合物及其活性组合物和应用 | |
| CN107638304A (zh) | 一种高皮肤细胞渗透的α‑熊果苷组合物及其制备方法和应用 | |
| DE69723725T2 (de) | Verfahren zur herstellung von konzentrierten lösungen von fibronectin ohne puffer | |
| CN101011354B (zh) | 细辛脑亚微乳制剂及其制备方法 | |
| CN114886878B (zh) | 18β-甘草次酸脂质体及其制备方法和应用 | |
| Babül et al. | The effect of EGF application in gel form on histamine content of experimentally induced wound in mice | |
| CN103330679B (zh) | 一种用于治疗鸽子体表寄生虫的涂膜剂及其制备方法 | |
| CN111714475A (zh) | 和厚朴酚在制备治疗和/或预防玫瑰痤疮的药物中的用途 | |
| TWI686211B (zh) | 易於穿透之包覆吉西他濱（Gemcitabine）及順鉑（Cisplatin）組合物 | |
| RU2326661C1 (ru) | Способ лечения хронического атрофического фарингита | |
| Toleubayev | Topical Polydeoxyribonucleotide Loaded in Hydrogel Formulation for Wound Healing in Diabetic Rats | |
| WO2024037545A1 (zh) | 右美托咪定经皮组合物、透皮贴剂及其制备方法和应用 | |
| CN115624520A (zh) | 一种地奥司明乳膏剂和应用 | |
| CN112823784A (zh) | 吡诺克辛钠滴眼液以及用于眼部给药的溶液 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20170714 |