CN108403619A - A kind of drug gel preparation treated hydrofluoric acid and cause skin burn - Google Patents
A kind of drug gel preparation treated hydrofluoric acid and cause skin burn Download PDFInfo
- Publication number
- CN108403619A CN108403619A CN201810326881.4A CN201810326881A CN108403619A CN 108403619 A CN108403619 A CN 108403619A CN 201810326881 A CN201810326881 A CN 201810326881A CN 108403619 A CN108403619 A CN 108403619A
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- CN
- China
- Prior art keywords
- preparation
- acritamer
- drug
- drug gel
- calcium gluconate
- 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.)
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Classifications
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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
-
- 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
- A61K47/30—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
-
- 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
Abstract
The present invention relates to a kind of drug gel preparations treated hydrofluoric acid and cause skin burn, and said preparation includes calcium gluconate, poloxamer188 and modifying agent, and it is 1 that wherein modifying agent, which is weight ratio,:1‑1:3 Acritamer 940 and the mixture of PLURONICS F87.The present invention improves the performance of drug gel, significantly improves the therapeutic effect of calcium gluconate preparation by the way that modifying agent is added in gelling agent.
Description
Technical field
The present invention relates to drug fields, and in particular to a kind of pharmaceutical preparation treated hydrofluoric acid and cause skin burn.
Background technology
Hydrofluoric acid (hydrofluoric acid, HF) is a kind of inorganic acid with high risk, is used extensively
In chemical industry, electronics manufacturing, glass etching, smelting and the daily fields such as keep a public place clean.HF can by skin and mucosa, alimentary canal,
The approach such as respiratory tract enter human body, not only have strong corrosiveness to local organization, can also cause general toxic reaction.
The HF burns of 2.5% total body surface area (Total Body Surface Area, TBSA) can cause death.
The fluorine-containing new material industry of China is mainly distributed on Zhejiang, has the fluorine chemical base of Largest In China inside the province, and exist
Periphery forms industry cluster.400,000 tons of hydrofluoric acid is produced in thoroughfare area per year, and a quarter for accounting for national total amount is strong.These fluorination work enterprises
Industry or production HF, the metal casting, glass processing and Electronic products manufacturing enterprise or using HF as raw material, and in Zhejiang Province are close
Collection, low concentration HF are widely used as cleaning agent in these enterprises, in production, overhaul of the equipments, transport and use the mistake of HF
Cheng Zhong, HF burn are difficult to avoid that group HF burn events happen occasionally.It is burnt by Zhejiang Province for one and gives treatment to instructing center tissue
Zhejiang Province's chemical burn epidemiological survey of completion shows, 1 day to 2009 August of September in 2008 31 days, 25 in Zhejiang Province
In 492 chemical burn patients that hospital's burns unit is hospitalized, HF burns account for 135, cause causing injury for chemical burn all
It ranks the first in chemicals.And newest epidemiological survey is shown, the incidence of Zhejiang area hydrofluoric acid burn becomes in rising
Gesture.Therefore, the correct understanding to the treatment Restoration Mechanism of HF burnt degrees is improved, is appropriately controlled in time using suitable pharmaceutical preparation
Treat HF burns has positive effect to patient.
The emergency treatment principle of HF burnt degrees removes chemical substance substantially conforming to the treatment principle of chemical lesion,
Systemic toxicity profiles symptom is treated, immunotherapy targeted autoantibody measure is taken for different chemical substances.But due to the particularity that HF causes injury, exposure
The processing of part is particularly important.The treatment key of HF burns is to block the damage of fluorine ion, and most common neutralizer is Portugal
Grape Calciofon.
The administration route of skin HF burnt degree calcium gluconates includes that surface of a wound external application, arterial perfusion and regional vein fill
Note, local subcutaneous injection.Calcium gluconate can be used for local wet dressing, and gel external application can also be made.That gel external application has is convenient,
Fast, the advantages of being convenient for repeat administration, is particularly suitable for the treatment of the local lesion caused by HF.
Situ-gel (in situ ge1), gel also known as in place, due to it does not need organic solvent or copolyreaction reagent
As the hot spot of Recent study.It specifically refers to after the high molecular material containing drug is administered in the form of a solution, in environmental stimuli
Lower generation phase transition, the new formulation of the semisolid or solid that are formed in agents area.According to mechanism of action difference, situ-gel
Responsive to temperature type, pH responsive types, ion-sensitive type, photaesthesia type etc. can be divided into.Wherein grinding with thermosensitive in situ gel
Study carefully the most extensively and ripe.Common high molecular material is divided into natural and 2 major class of synthesis, the former includes cellulose and its derivative
Object, chitosan and phosphoglycerol, xylan etc., the latter's such as poloxamer (Poloxamer), PEO/PLGA, PEG-PLGA-PEG
Copolymer etc..
Poloxamer block copolymer (Poloxamer copolymer) is introduced in the later stage fifties, later extensive use
In pharmaceutical field, included by US and European pharmacopeia.It is total to by 3 sections that polyoxyethylene (EO) and polyoxypropylene (PO) form
Polymers.Poloxamer188 (Poloxamer407, P407) is averaged with 7: 3 composition of proportions by polyoxyethylene and polyoxypropylene
Relative molecular mass is 11500, and trade name is Pluronic (F-127).Poloxamer188 aqueous solution has temperature sensitivity
Matter, but exact gelling mechanism is unclear.
Currently, in the prior art there is not yet for the efficient calcium gluconate gel preparation for treating hydrofluoric acid burn.
Invention content
To overcome the deficiencies of existing technologies, the present invention provides a kind of calcium gluconate gel preparation, which uses
Aspect is convenient for repeat administration, causes skin burn significant in efficacy in treatment hydrofluoric acid.
Specifically, one aspect of the present invention provides：
A kind of drug gel preparation treated hydrofluoric acid and cause skin burn, the preparation include calcium gluconate, Bo Luosha
Nurse 407 and modifying agent, wherein modifying agent are the mixture of Acritamer 940 and PLURONICS F87.
In a preferred embodiment, the weight ratio of the Acritamer 940 and PLURONICS F87 is 1:1-1:3.
In a preferred embodiment, the weight ratio of the Acritamer 940 and PLURONICS F87 is 1:2.
In a preferred embodiment, the weight percent of calcium gluconate is 1-5% in preparation.
In a preferred embodiment, the weight percent of calcium gluconate is 3% in preparation.
In a preferred embodiment, the weight percent of poloxamer188 is 10-20% in preparation.
In a preferred embodiment, the weight percent of poloxamer188 is 12-16% in preparation.
In a preferred embodiment, the weight percent of poloxamer188 is 14% in preparation.
In a preferred embodiment, the weight percent of the mixture of Acritamer 940 and PLURONICS F87 is in preparation
1-5%.
In a preferred embodiment, the weight percent of the mixture of Acritamer 940 and PLURONICS F87 is in preparation
3%.
In a preferred embodiment, the weight percent of Acritamer 940 is 1% in preparation, the weight of PLURONICS F87
Percentage is 2%.
Second aspect of the present invention provides：
The preparation method of said medicine gel preparation, step include：Poloxamer188 is dissolved under room temperature pure
Acritamer 940 and PLURONICS F87 are added in water purification, under stirring condition to abundant dissolving, Portugal is added after above-mentioned solution is heated
Grape Calciofon, stirring make it fully dissolve to get calcium gluconate gel.
In a preferred embodiment, calcium gluconate is added after being heated to 80 DEG C in the solution.
In a preferred embodiment, being stirred 1 hour after addition calcium gluconate makes it fully dissolve.
Third aspect present invention provides：
Application of the above-mentioned gel preparation in preparing treatment hydrofluoric acid and causing skin burn drug.
The advantages of present invention obtains and good effect：
The present invention optimizes the property of gel by the way that modifying agent Acritamer 940 and PLURONICS F87 are added in drug gel
Can, the transdermal permeation characteristics of drug in gel are improved, improve drug effect in the therapeutic effect in burn affected part.Unexpected
It is, when Acritamer 940 in modifying agent and PLURONICS F87 are with 1:1-1:When 3 weight ratio collocation, the treatment effect of drug in gel
Fruit, which produces, is difficult to expected excellent effect.
Specific implementation mode
Below by specific embodiment, the invention will be further described, and following embodiment is descriptive, is not limit
Qualitatively, protection scope of the present invention cannot be limited with this.
Raw material used in the present invention is unless otherwise specified conventional commercial product；Used in the present invention
Method is unless otherwise specified the conventional method of this field.
One, the preparation of calcium gluconate gel
Embodiment 1：
14g poloxamer188s are dissolved in 80g pure water under room temperature, 1g Acritamer 940s are added under stirring condition
With 2g PLURONICS F87s to abundant dissolving, 3g calcium gluconates are added after heating the solution to 80 DEG C, stirring makes for 1 hour
It is fully dissolved to get calcium gluconate gel G1.
Embodiment 2：
14g poloxamer188s are dissolved in 80g pure water under room temperature, 1.5g carbomers are added under stirring condition
3g calcium gluconates are added to abundant dissolving in 940 and 1.5g PLURONICS F87s after heating the solution to 80 DEG C, stirring 1 is small
When so that it is fully dissolved to get calcium gluconate gel G2.
Embodiment 3：
14g poloxamer188s are dissolved in 80g pure water under room temperature, 0.75g carbomers are added under stirring condition
3g calcium gluconates, stirring 1 is added to abundant dissolving in 940 and 2.25g PLURONICS F87s after heating the solution to 80 DEG C
Hour makes it fully dissolve to get calcium gluconate gel G3.
Embodiment 4：
14g poloxamer188s are dissolved in 80g pure water under room temperature, 3g Acritamer 940s are added under stirring condition
To abundant dissolving, be added 3g calcium gluconates after heating the solution to 80 DEG C, stirring so that it is fully dissolved within 1 hour to get
Calcium gluconate gel G4.
Embodiment 5：
14g poloxamer188s are dissolved in 80g pure water under room temperature, 3g poloxamers are added under stirring condition
188, to abundant dissolving, are added 3g calcium gluconates after heating the solution to 80 DEG C, stirring makes it fully dissolve in 1 hour, i.e.,
Obtain calcium gluconate gel G5.
Two, therapeutic effect of the calcium gluconate gel preparation to rat hydrofluoric acid burn
1, the foundation of rat hydrofluoric acid burn model
Rat after carbrital (30 mg/kg) intraperitoneal anesthesia, using barium sulphide lose hair or feathers by back.Raising 24 hours
Afterwards, 40% hydrofluoric acid solution is uniformly applied to rat back with cotton swab, causes (3 3 centimetres of cm x) about 3.4%TBSA burn wounds
Burned part is rinsed 1 minute in face after 3 minutes with tap water, spare.
2, the dosage regimen of calcium gluconate gel preparation
The rat for 60 being established only according to the above method hydrofluoric acid burn model is randomly divided into 6 groups, every group 10.Wherein 1
Group is blank control group, remaining 5 groups are drug gel treatment group.The rat of 5 drug gel treatment groups is molten in application hydrofluoric acid
Liquid started to be treated with gel preparation (G1-G5) prepared by embodiment 1-5 after 1 hour, and every rat applies gel preparation
Dosage is 1g.
3, the therapeutic effect of calcium gluconate gel preparation
Rat in blank group is measured respectively to control using 30 minutes after etching acid cutaneous necrosis areas and each drug gel
Rat applies cutaneous necrosis area of the gel preparation (G1-G5) after 3 days in treatment group, and every rat measures 3 times, is averaged.
Wherein, the circular of necrosis area is：
S=π * [(L+W)/4]2, L is the length of necrosis area in calculation formula, and W is the width of necrosis area.
30 minutes after hydrogen fluoride cutaneous necrosis area (average value of rat necrosis area in group) work is applied with blank group
For 100% standard, calculates each drug gel treatment group and (organize interior rat necrosis area using rat skin necrosis area after 3 days
Average value) relative percentage, and as evaluation drug gel group therapeutic effect index.Each drug gel treatment group pair
The repairing effect of necrosis area is as shown in table 1 after hydrofluoric acid cause burn injury in rats.
1 each drug gel treatment group of table causes hydrofluoric acid the influence of burn injury in rats necrosis area
As can be seen from Table 1, when addition Acritamer 940 in calcium gluconate gel and PLURONICS F87 mixing
When object (G1-G3 groups), exclusive use Acritamer 940 that gel preparation is substantially better than the reparation of necrosis area after burn injury in rats
Or test group (G4 and G5 group) of the PLURONICS F87 as accelerating agent.More surprisingly, the feelings constant in modifying agent total amount
Under condition, when the weight ratio of Acritamer 940 in modifying agent and PLURONICS F87 is 1:When 2 (G1 groups), to burn injury in rats area
Repairing effect is much better than the test group (G2 and G3 groups) of other proportionings, produces and is difficult to expected therapeutic effect.
Claims (10)
1. a kind of drug gel preparation treated hydrofluoric acid and cause skin burn, which is characterized in that the preparation includes gluconic acid
Calcium, poloxamer188 and modifying agent, wherein modifying agent are the mixture of Acritamer 940 and PLURONICS F87.
2. drug gel preparation according to claim 1, which is characterized in that Acritamer 940 and pool Lip river in the modifying agent
The weight ratio of husky nurse 188 is 1:1-1:3.
3. drug gel preparation according to claim 2, which is characterized in that Acritamer 940 and pool Lip river in the modifying agent
The weight ratio of husky nurse 188 is 1:2.
4. according to claim 1-3 any one of them drug gel preparations, which is characterized in that calcium gluconate in the preparation
Weight percent be 1-5%.
5. according to claim 1-3 any one of them drug gel preparations, which is characterized in that poloxamer in the preparation
407 weight percent is 10-20%.
6. according to claim 1-3 any one of them drug gel preparations, which is characterized in that Acritamer 940 in the preparation
Weight percent with the mixture of PLURONICS F87 is 1-5%.
7. a kind of preparation method of any one of claim 1-6 drug gel preparations, which is characterized in that under room temperature will
Poloxamer188 is dissolved in pure water, adds Acritamer 940 and PLURONICS F87, is sufficiently stirred dissolving, will be above-mentioned molten
Calcium gluconate is added after liquid heating, stirring makes it fully dissolve to get calcium gluconate gel preparation.
8. preparation method according to claim 7, which is characterized in that calcium gluconate is added after being heated to 80 DEG C in solution.
9. preparation method according to claim 7, which is characterized in that being stirred 1 hour after addition calcium gluconate makes it fill
Divide dissolving.
10. claim 1-6 any one of them drug gel preparations are in preparing treatment hydrofluoric acid and causing the drug of skin burn
Application.
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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108403619A true CN108403619A (en) | 2018-08-17 |
| CN108403619B CN108403619B (en) | 2021-03-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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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Cited By (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 (4)
| 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 |
| US20150005380A1 (en) * | 2012-02-27 | 2015-01-01 | Assistance Publique-Hopitaux De Paris | Gelling Formulation Based On Calcium Gluconate |
-
2018
- 2018-04-12 CN CN201810326881.4A patent/CN108403619B/en not_active Expired - Fee Related
Patent Citations (4)
| 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 |
| US20150005380A1 (en) * | 2012-02-27 | 2015-01-01 | Assistance Publique-Hopitaux De Paris | Gelling Formulation Based On Calcium Gluconate |
| 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 |
|---|
| D. THOMAS ET AL: "Intra-Arterial Calcium Gluconate Treatment After Hydrofluoric Acid Burn of the Hand", 《CARDIOVASC INTERVENT RADIOL》 * |
| ISABELLE ROBLIN ET AL: "Topical Treatment of Experimental Hydrofluoric Acid Skin Burns by 2.5% Calcium Gluconat", 《JOURNAL OF BURN CARE & RESEARCH》 * |
| 刘利平，等: "葡萄糖酸钙凝胶治疗手足部氢氟酸烧伤的疗效观察", 《中华烧伤杂志》 * |
| 李星，等: "温度敏感型布洛芬缓释液体栓的制备与体内外评价", 《中国医院药学杂志》 * |
Cited By (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 |
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| CN108403619B (en) | 2021-03-02 |
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