CN108403619B - Medicinal gel preparation for treating skin burn caused by hydrofluoric acid - Google Patents
Medicinal gel preparation for treating skin burn caused by hydrofluoric acid Download PDFInfo
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- CN108403619B CN108403619B CN201810326881.4A CN201810326881A CN108403619B CN 108403619 B CN108403619 B CN 108403619B CN 201810326881 A CN201810326881 A CN 201810326881A CN 108403619 B CN108403619 B CN 108403619B
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- Prior art keywords
- calcium gluconate
- gel
- poloxamer
- hydrofluoric acid
- carbomer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
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- 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
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- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a medicinal gel preparation for treating skin burn caused by hydrofluoric acid, which comprises calcium gluconate, poloxamer407 and a modifier, wherein the modifier is a mixture of carbomer 940 and poloxamer 188 in a weight ratio of 1:1-1: 3. According to the invention, the modifier is added into the gel, so that the performance of the medicine gel is improved, and the treatment effect of the calcium gluconate preparation is obviously improved.
Description
Technical Field
The invention relates to the field of medicaments, in particular to a medicinal preparation for treating skin burn caused by hydrofluoric acid.
Background
Hydrofluoric acid (HF) is a highly dangerous inorganic acid and is now widely used in the fields of chemical industry, electronics manufacturing, glass etching, smelting, and daily sanitation. HF can enter human body through skin mucous membrane, digestive tract, respiratory tract and other ways, not only has strong corrosive action on local tissues, but also can cause systemic toxic reaction. HF burns of 2.5% Total Body Surface Area (TBSA) can cause death.
The fluorine-containing new material industry in China is mainly distributed in Zhejiang, has the largest fluorine chemical base in China in province, and forms an industry cluster around the country. The annual hydrofluoric acid yield of the thoroughfare area is 40 million tons, which accounts for one fourth of the total amount of the whole country. The fluorine chemical enterprises can produce HF, or use HF as raw material, and metal casting, glass processing and electronic product manufacturing enterprises in Zhejiang province are dense, and low-concentration HF is used as cleaning agent, and the cleaning agent is widely applied in the enterprises, HF burns are difficult to avoid in the processes of production, equipment maintenance, transportation and use of HF, and mass HF burns happen occasionally. An epidemiological survey of chemical burns in Zhejiang province completed by Zhejiang province burn treatment guidance center organization shows that 9.1 to 2009 in 2008 is 31, among 492 cases of chemical burns patients in 25 hospital burn surgery hospitalization in Zhejiang province, HF burns account for 135 cases and are ranked first among all the chemical burns causing chemical burns. Recent epidemiological survey shows that the incidence of hydrofluoric acid burn in Zhejiang is on the rise. Therefore, the correct understanding of the treatment and recovery mechanism after HF burns is improved, and the proper and timely use of proper pharmaceutical preparations for treating HF burns has positive significance for patients.
The emergency treatment principle after HF burns basically conforms to the treatment principle of chemical injury, namely chemical substances are removed, the systemic toxic symptoms are treated, and targeted treatment measures are taken according to different chemical substances. However, due to the particularities of HF-induced injury, the treatment of exposed areas is particularly important. The key to the treatment of HF burns is to block the damage of fluoride ions, the most commonly used neutralizing agent is calcium gluconate.
The administration routes of calcium gluconate after skin HF burns include wound external application, arterial infusion, regional venous infusion and local subcutaneous injection. The calcium gluconate can be used for topical wet compress, or made into gel for external use. The gel has the advantages of convenient and quick application and convenient repeated administration, and is particularly suitable for treating local damage caused by HF.
In situ gel (in situ ge1), also known as in situ gel, has been the focus of recent research because it does not require organic solvents or copolymerization reagents. In particular to a novel semisolid or solid preparation which is formed at an application part by phase transition under external stimulation after a high molecular material containing a medicament is administrated in a solution form. According to different action mechanisms, the in-situ gel can be divided into a temperature sensitive type, a pH sensitive type, an ion sensitive type, a light sensitive type and the like. Among them, the temperature sensitive in situ gel is the most widely and mature. The commonly used polymer materials are classified into 2 types, i.e., natural and synthetic, the former includes cellulose and its derivatives, chitosan and glycerophosphoric acid, xylan, etc., and the latter includes Poloxamer (Poloxamer), PEO/PLGA, PEG-PLGA-PEG copolymer, etc.
Poloxamer block copolymers (Poloxamer copolymers) were introduced in the late 50 s and have been widely used in the pharmaceutical field since then and are being included in the united states and european pharmacopoeias. It is a 3-stage copolymer consisting of polyoxyethylene (EO) and Polyoxypropylene (PO). Poloxamer407 (Poloxamer407, P407) is composed of polyoxyethylene and polyoxypropylene in a ratio of 7: 3, and has an average relative molecular mass of 11500, under the trade name Pluronic (F-127). Poloxamer407 aqueous solution has temperature sensitive properties, but the exact gelling mechanism is not clear.
At present, no calcium gluconate gel preparation for efficiently treating hydrofluoric acid burn is available in the prior art.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a calcium gluconate gel preparation which is convenient to repeatedly administer in use and has obvious curative effect on treating skin burn caused by hydrofluoric acid.
Specifically, one aspect of the present invention provides:
a pharmaceutical gel preparation for treating skin burn caused by hydrofluoric acid comprises calcium gluconate, poloxamer407 and a modifying agent, wherein the modifying agent is a mixture of carbomer 940 and poloxamer 188.
In a preferred embodiment, the weight ratio of carbomer 940 to poloxamer 188 is from 1:1 to 1: 3.
In a preferred embodiment, the weight ratio of carbomer 940 to poloxamer 188 is 1: 2.
In a preferred embodiment, the weight percentage of calcium gluconate in the formulation is 1-5%.
In a preferred embodiment, the weight percentage of calcium gluconate in the formulation is 3%.
In a preferred embodiment, poloxamer407 is present in the formulation in an amount of 10-20% by weight.
In a preferred embodiment, poloxamer407 is present in the formulation in an amount of 12-16% by weight.
In a preferred embodiment, poloxamer407 is present in the formulation in an amount of 14% by weight.
In a preferred embodiment, the weight percentage of the mixture of carbomer 940 and poloxamer 188 in the formulation is 1-5%.
In a preferred embodiment, the weight percentage of the mixture of carbomer 940 and poloxamer 188 in the formulation is 3%.
In a preferred embodiment, the formulation has 1% carbomer 940 by weight and 2% poloxamer 188 by weight.
The second aspect of the present invention provides:
the preparation method of the medicinal gel preparation comprises the following steps: dissolving poloxamer407 in purified water at room temperature, adding carbomer 940 and poloxamer 188 under stirring to dissolve completely, heating the solution, adding calcium gluconate, and stirring to dissolve completely to obtain calcium gluconate gel.
In a preferred embodiment, the solution is heated to 80 ℃ before adding calcium gluconate.
In a preferred embodiment, calcium gluconate is added and stirred for 1 hour to dissolve it sufficiently.
A third aspect of the present invention provides:
the gel preparation is applied to the preparation of the medicine for treating skin burn caused by hydrofluoric acid.
The invention has the advantages and positive effects that:
according to the invention, the modifier carbomer 940 and poloxamer 188 are added into the medicine gel, so that the performance of the gel is optimized, the transdermal property of the medicine in the gel is improved, and the treatment effect of the medicine on the burn affected part is improved. Surprisingly, the therapeutic effect of the drug in the gel produced unexpected superior effects when carbomer 940 and poloxamer 188 are combined in the modifier in a weight ratio of 1:1 to 1: 3.
Detailed Description
The present invention is further illustrated by the following specific examples, which are intended to be illustrative, not limiting and are not intended to limit the scope of the invention.
The raw materials used in the invention are conventional commercial products unless otherwise specified; the methods used in the present invention are conventional in the art unless otherwise specified.
Preparation of calcium gluconate gel
Example 1:
dissolving 14G of poloxamer407 in 80G of purified water at room temperature, adding 1G of carbomer 940 and 2G of poloxamer 188 under stirring until the poloxamer 940 and the poloxamer 188 are fully dissolved, heating the solution to 80 ℃, adding 3G of calcium gluconate, and stirring for 1 hour to fully dissolve the calcium gluconate gel G1.
Example 2:
dissolving 14G of poloxamer407 in 80G of purified water at room temperature, adding 1.5G of carbomer 940 and 1.5G of poloxamer 188 under stirring until the materials are fully dissolved, heating the solution to 80 ℃, adding 3G of calcium gluconate, and stirring for 1 hour to fully dissolve the calcium gluconate gel G2.
Example 3:
dissolving 14G of poloxamer407 in 80G of purified water at room temperature, adding 0.75G of carbomer 940 and 2.25G of poloxamer 188 under stirring until the materials are fully dissolved, heating the solution to 80 ℃, adding 3G of calcium gluconate, and stirring for 1 hour to fully dissolve the calcium gluconate gel G3.
Example 4:
dissolving 14G of poloxamer407 in 80G of purified water at room temperature, adding 3G of carbomer 940 under stirring to fully dissolve the poloxamer407, heating the solution to 80 ℃, adding 3G of calcium gluconate, and stirring for 1 hour to fully dissolve the calcium gluconate to obtain calcium gluconate gel G4.
Example 5:
dissolving 14G of poloxamer407 in 80G of purified water at room temperature, adding 3G of poloxamer 188 under stirring until the poloxamer 188 is fully dissolved, heating the solution to 80 ℃, adding 3G of calcium gluconate, and stirring for 1 hour to fully dissolve the calcium gluconate gel G5.
Second, the therapeutic action of the calcium gluconate gel preparation on the hydrofluoric acid burn of rats
1. Establishment of hydrofluoric acid burn model of rat
Rats were anesthetized in the abdominal cavity with pentobarbital sodium (30 mg/kg) and then depilated on the back with barium sulfide. After 24 hours of feeding, the rats were evenly smeared with a 40% hydrofluoric acid solution on their backs with a cotton swab to create (3 cm. times.3 cm) burn wounds of about 3.4% TBSA, and the burn sites were rinsed with tap water for 1 minute after 3 minutes for use.
2. Dosing regimen for calcium gluconate gel formulations
60 rats with hydrofluoric acid burn models established as described above were randomly divided into 6 groups of 10 rats each. Wherein 1 group is blank control group, and the other 5 groups are drug gel treatment groups. Rats of 5 drug gel treatment groups were initially treated with the gel formulations prepared in examples 1-5 (G1-G5) 1 hour after administration of a hydrofluoric acid solution, and the dose of the gel formulation was 1G per rat.
3. Therapeutic effect of calcium gluconate gel preparation
The area of skin necrosis 30 minutes after the administration of hydrofluoric acid to the rats in the blank group and the area of skin necrosis 3 days after the administration of the gel formulation (G1-G5) to the rats in each drug gel treatment group were measured, 3 times per rat, respectively, and averaged.
The specific calculation method of the necrosis area comprises the following steps:
S＝π*[(L+W)/4]2in the calculation formula, L is the length of the necrotic area, and W is the width of the necrotic area.
The relative percentage of the necrotic area on the skin of rats (the average of the necrotic areas on the rats in the group) 3 days after the administration of each drug gel treatment group was calculated using the necrotic area on the skin 30 minutes after the administration of hydrogen fluoride in the blank group (the average of the necrotic areas on the rats in the group) as a 100% standard, and was used as an index for evaluating the treatment effect of the drug gel group. The repairing effect of each drug gel treatment group on the necrotic area of rats caused by hydrofluoric acid after burn is shown in table 1.
Table 1 influence of each drug gel treatment group on hydrofluoric acid-induced burn necrosis area of rats
As can be seen from the data in Table 1, when a mixture of carbomer 940 and poloxamer 188 is added to the calcium gluconate gel (groups G1-G3), the gel formulation is significantly better for repairing the post-burn necrotic area in rats than the test groups using carbomer 940 or poloxamer 188 alone as the accelerator (groups G4 and G5). More surprisingly, the effect of repairing the burned area of rats was much better than that of the test groups (groups G2 and G3) with the other ratios, when the weight ratio of carbomer 940 to poloxamer 188 in the modifier was 1:2 (group G1), with the total amount of the modifier being unchanged, resulting in unexpected therapeutic effect.
Claims (6)
1. The medicinal gel preparation for treating skin burn caused by hydrofluoric acid is characterized by comprising calcium gluconate, poloxamer407 and a modifier, wherein the modifier is a mixture of carbomer 940 and poloxamer 188, the weight ratio of the carbomer 940 to the poloxamer 188 in the modifier is 1:2, the weight percentage of the poloxamer407 in the preparation is 10-20%, and the weight percentage of the mixture of the carbomer 940 and the poloxamer 188 in the preparation is 1-5%.
2. The pharmaceutical gel formulation of claim 1, wherein the weight percentage of calcium gluconate in said formulation is 1-5%.
3. A process for preparing a pharmaceutical gel formulation according to claim 1 or 2, wherein poloxamer407 is dissolved in purified water at room temperature, carbomer 940 and poloxamer 188 are added, the mixture is thoroughly stirred and dissolved, the solution is heated, calcium gluconate is added, and the mixture is thoroughly stirred and dissolved to obtain a calcium gluconate gel formulation.
4. The method of claim 3, wherein the calcium gluconate is added after the solution is heated to 80 ℃.
5. The method according to claim 3, wherein the calcium gluconate is added and then stirred for 1 hour to be sufficiently dissolved.
6. Use of a pharmaceutical gel formulation according to claim 1 or 2 in the manufacture of a medicament for the treatment of hydrofluoric acid induced skin burn.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810326881.4A CN108403619B (en) | 2018-04-12 | 2018-04-12 | Medicinal gel preparation for treating skin burn caused by hydrofluoric acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810326881.4A CN108403619B (en) | 2018-04-12 | 2018-04-12 | Medicinal gel preparation for treating skin burn caused by hydrofluoric acid |
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| Publication Number | Publication Date |
|---|---|
| CN108403619A CN108403619A (en) | 2018-08-17 |
| CN108403619B true CN108403619B (en) | 2021-03-02 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201810326881.4A Expired - Fee Related CN108403619B (en) | 2018-04-12 | 2018-04-12 | Medicinal gel preparation for treating skin burn caused by hydrofluoric acid |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110151782A (en) * | 2019-06-19 | 2019-08-23 | 天津市恒兴化学试剂制造有限公司 | It is a kind of for alleviating the cleaning solution of hydrofluoric acid burn |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63104914A (en) * | 1986-10-23 | 1988-05-10 | Mitsubishi Kasei Corp | Skin preparation |
| EP2145617A1 (en) * | 2008-04-04 | 2010-01-20 | Ludzker, Benjamin | Gel formulation |
| CN104027299A (en) * | 2014-06-13 | 2014-09-10 | 暨南大学 | Itraconazole temperature-sensitive type gel preparation as well as preparation method and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2987269B1 (en) * | 2012-02-27 | 2014-04-18 | Hopitaux Paris Assist Publique | GELIFYING FORMULATION BASED ON CALCIUM GLUCONATE |
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2018
- 2018-04-12 CN CN201810326881.4A patent/CN108403619B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63104914A (en) * | 1986-10-23 | 1988-05-10 | Mitsubishi Kasei Corp | Skin preparation |
| EP2145617A1 (en) * | 2008-04-04 | 2010-01-20 | Ludzker, Benjamin | Gel formulation |
| CN104027299A (en) * | 2014-06-13 | 2014-09-10 | 暨南大学 | Itraconazole temperature-sensitive type gel preparation as well as preparation method and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| Intra-Arterial Calcium Gluconate Treatment After Hydrofluoric Acid Burn of the Hand;D. Thomas et al;《Cardiovasc Intervent Radiol》;20080528(第32期);第155-158页 * |
| Topical Treatment of Experimental Hydrofluoric Acid Skin Burns by 2.5% Calcium Gluconat;Isabelle Roblin et al;《Journal of Burn Care & Research》;20061231;第27卷(第6期);第889-894页 * |
| 温度敏感型布洛芬缓释液体栓的制备与体内外评价;李星，等;《中国医院药学杂志》;20110930;第31卷(第17期);第1411页左栏第1段、第1-2节 * |
| 葡萄糖酸钙凝胶治疗手足部氢氟酸烧伤的疗效观察;刘利平，等;《中华烧伤杂志》;20140228;第30卷(第1期);第67-69页 * |
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Granted publication date: 20210302 |