CN101947200A - Emulsion type ointment - Google Patents
Emulsion type ointment Download PDFInfo
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- CN101947200A CN101947200A CN2010102410572A CN201010241057A CN101947200A CN 101947200 A CN101947200 A CN 101947200A CN 2010102410572 A CN2010102410572 A CN 2010102410572A CN 201010241057 A CN201010241057 A CN 201010241057A CN 101947200 A CN101947200 A CN 101947200A
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- water type
- type ointment
- alginic acid
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Abstract
The invention relates to an emulsion type ointment which comprises alginic acid and salts thereof, an emulsifier, a cross-linking agent, an oil-based agent and a water-based agent, wherein the oil-based agent accounts for 10%-85% by weight of the emulsion type ointment, the alginic acid and the salts thereof account for not more than 7% by weight of the emulsion type ointment, the emulsifier accounts for not lower than 1% and not higher than 30% by weight of the emulsion type ointment, and weight ratio of the cross-linking agent to the alginic acid and the salts thereof is not lower than 1:10 and not higher than 5:1, and the remaining is the water-based agent. Materials adopted for the ointment have low price and can be obtained easily, the preparation route is simple, and the product has strong stability and is stable without layer separation when standing at 30 DEG C for one year.
Description
One, technical field
The invention belongs to the pharmaceutical dosage form preparing technical field, particularly a kind of emulsifying ointments pharmaceutical dosage form.This ointment can be used for profit mixed type drug system, or the emulsifiable pasteization of oil-soluble medicine system.
Two, background technology
Ointment is that medicine is added a kind of paste external preparation with d spiss of coating skin, mucosa or wound surface easily of making in the suitable substrate.General substrate requires lubricated non-stimulated, and denseness is suitable, is easy to coating; Compatibility does not take place with main medicine and changes in stable in properties; Have water absorption, can absorb wound exudate; Do not hinder the normal function of skin, have good Release Performance, clothes is not polluted in easily eccysis.Thicken at epidermis, burn and scald festers, keratinization, and acute and chronic skin lesion or some infectious skin disease such as chap all are suitable in early days.
To form complexity be the outstanding feature of skin indication to adjuvant in the traditional soft paste formulation.No matter be the medicine of new drug, import drugs or existing national standard, often contain tens kinds of adjuvants in the prescription.So numerous adjuvants is formed rational research for prescription and is brought great difficulty, and drug safety has been brought great hidden danger.Research data is difficult to the mutual relation and the consumption foundation of clear and definite numerous adjuvants, the effect of clear and definite each adjuvant in prescription and quite complicated to the influence of medicine in the cream preparation, therefore the accessory formula of ointment formulation is simple more, the few more influence to medicine of consumption is more little, safety is high more, and the problem of formulation and technology part Study existence at present is mainly reflected in:
(1) arbitrarily add composition in the prescription with pharmacologically active, its large usage quantity, and reached medicinal concentration, the classification of medicine is changed.Compositions such as for example the local skin external preparation arbitrarily camphorates in writing out a prescription, Borneolum Syntheticum, these compositions itself have certain pharmacologically active, can cause that pharmaceutical effectiveness changes.
(2) add non-external preparation adjuvant commonly used in the prescription.As a class medicine for external use, because the principal agent poor solubility, so the developer adopts acetone to make solvent in prescription, and principal agent is dissolved.But acetone is as a kind of organic solvent, and ICH is defined as three kind solvents with it, and its residual quantity needs control.Though be external preparation, safety after acetone percutaneous in the life-time service process absorbs and life-time service all need to pay close attention to the safety issues such as zest of skin.Therefore, will the important directions of drug manufacture technological development as excipient substance with the non-irritating material of pure natural.
(3) be difficult to determine to meet the adjuvant quality control standard of medicinal requirements.The Quality Control of adjuvant is determining the stability of product quality to a certain extent, though can accomplish that each adjuvant all meets national standard in the prescription, but kind and its reciprocal action that adjuvant adds are difficult to understand in depth, therefore are difficult to guarantee the quality of preparation and the safety of clinical use.
Three, summary of the invention
Goal of the invention: the invention provides a kind of oil-in-water type ointment, the material price that this ointment adopted is cheap easily to be obtained, and the preparation route is simple and product stability is strong, and 30 ℃ leave standstill an average annual stable no layering.
Technical scheme: a kind of oil-in-water type ointment, this ointment comprises alginic acid and salt, emulsifying agent, cross-linking agent, oiliness base and aqueous base, wherein the oiliness base accounts for the mass ratio of oil-in-water type ointment between 10%-85%, alginic acid and salt thereof shared mass ratio in oil-in-water type ointment is not more than 7%, emulsifying agent shared mass ratio in oil-in-water type ointment is not less than 1% and is not higher than 30%, cross-linking agent is not less than with the ratio of the adding quality of alginic acid and salt thereof in oil-in-water type ointment and is not higher than 5: 1 at 1: 10, remains to be the aqueous base.Described oiliness base is vegetable and animals oils or vegetable oil, and described vegetable and animals oils is: a kind of or any several mixture in paraffin, liquid paraffin, white vaseline, lanoline, hexadecanol, octadecanol, the glycerol etc.; Described vegetable oil is Oleum Ricini, Oleum Glycines, Oleum sesami or Cera Flava.Described aqueous base is the polar solvent that is insoluble to oil.Described alginic acid and salt thereof are one or more mixed-powders in potassium alginate, sodium alginate or the alginic acid.Described emulsifying agent is the serial emulsifying agent of class of department, twain series emulsifier or AOT, and the HLB value of used emulsifying agent is between 4-23.Described cross-linking agent is bivalent metal ion saline solution, chitosan or glutaraldehyde.The described polar solvent that is insoluble to oil is a distilled water.Described bivalent metal ion saline solution is: Ca
2+, Pb
2+, Cu
2+, Cd
2+, Co
2+, Ni
2+, Zn
2+Or Mn
2+Saline solution.The denseness and the viscosity of ointment are not less than 3.18mPa.s, and the percentage of water loss of emulsifying ointment 5h is not higher than 6.73%.Sodium alginate and chitosan form cross-linked network and microcapsule structure in gel, can play embedding fixation and sustained release effect to oil-soluble medicine.And these two kinds of materials all have excellent biological compatibility, and with emulsifying ointment and co-culture of cells, the good MTT of cell growth state detects and finds that seven days rates of increase of cell reach 98%.Emulsifying ointment Random Graph is distributed on volunteer's human body skin, washes with water behind the 1h and remove, the result shows that the emulsifying ointment is easy to coating, is easy to eluting, and human body skin does not have rubescent, plays phenomenons such as rash.
Beneficial effect: the material price that the present invention adopts is cheap easily to be obtained, the new technique that relates to, and route is simple, and is with high content of technology, and product stability is strong, and 30 ℃ leave standstill an average annual stable no layering.Sodium alginate itself has gel, suspending, thickening, emulsifying, effect such as bonding.The addition and the kind of adjuvant simplified in this research, only use alginic acid and salt thereof selecting for use of thickening agent, and it is optimized by emulsification system, by a step self-assembling reaction, make alginic acid and salt thereof in the emulsifiable paste system, form micelle by crosslinked and emulsification, and then encystation, Jiang Shui, oily mixed type medicine or oil-soluble medicine are wrapped in the microcapsule, not only can improve the oil-containing stability of drug and medicine is had the control slow releasing function.The material character that this emulsifiable paste is selected for use is stable, has no stimulation to skin is nontoxic.The medicine that contains oil phase by this method can be stable in the emulsus ointment system and the micelle that forms can be overlying on pharmaceutical pack the effect that wherein reaches controlled release fertilizer.This class emulsifiable paste not only can effectively be stablized the mixed type medicine, and microcapsule can play the control slow releasing function to medicine, pass through the hierarchy of control, this research can also be controlled the size of microgranule in the ointment, nano-scale particle can improve the penetrance of medicine, and micron particles can play massage effect, therefore can such emulsifiable paste be had simultaneously by the consumption that changes emulsifying agent and cross-linking agent and preserve moisture, massage, effects such as high infiltration.
The present invention has avoided the harmful effect that the multiple adjuvant of employing brings in the existing ointment technology, use is made the ointment adjuvant to skin and the non-stimulated natural material of mucosa, cost is low, consumptive material is few, the corresponding medicament contg that improved of minimizing of adjuvant in the ointment, has broad application prospects.
Four, description of drawings
Fig. 1 is the SEM photo of emulsifying ointment;
Fig. 2 is the SEM photo of common ointment.
Five, the specific embodiment
The invention will be further described below in conjunction with example:
One, the preparation of ointment
Embodiment 1:
Oleum Glycines, water mixed system, sodium alginate powder, calcium salt soln (calcium phosphate, calcium chloride, calcium carbonate etc. all can), distilled water, the tween system:
In Oleum Glycines, water mixed system, the emulsifier tween that adds finished product ointment 30%wt, sodium alginate is dissolved in the aqueous phase of profit mixed system, the ratio that addition accounts for finished product ointment weight is not less than 1%wt and is not more than 5%wt, stir more than 30 minutes being not less than under 500 revolutions per seconds the rotating speed, drip calcium salt soln at last, the weight ratio that dripping quantity accounts for finished product ointment is not less than 0.5% and is not more than 8%, promptly makes ointment formulation.The denseness of emulsifying ointment and viscosity (η c) are not less than 3.18mPa.s after testing, and percentage of water loss detects finds that the percentage of water loss of emulsifying ointment 5h is not higher than 6.73%wt.And these two kinds of materials all have excellent biological compatibility, and with emulsifying ointment and co-culture of cells, cell growth state is good, and MTT detects and finds that seven days rates of increase of cell reach 98%.Emulsifying ointment Random Graph is distributed on volunteer's human body skin, washes with water behind the 1h and remove, the result shows that the emulsifying ointment is easy to coating, is easy to eluting, and human body skin does not have rubescent, plays phenomenons such as rash.With ointment place the centrifugal 30min of rotating speed of 30 degree isoperibol 2500r/min, microexamination whether have layering or precipitation (pharmaceutics teaching and research group of Nanjing pharmaceutical college. pharmaceutics, the 2nd edition [M]. Beijing: the People's Health Publisher, 1985:854); Respectively at-15 ℃ of refrigerator 24h, 55 ℃ of calorstat 6h, whether observe has demulsifying phenomenon (Sun Shuying, Jiang Jie, Zhang Dongzeng, Deng. the dissolution in vitro and the stability experiment [J] of oil-in-water type ethoxy benzene willow amine ointment. dense positive pharmaceutical college journal, 1990,44 (7): 160), 37～40 ℃ of temperature, humidity preserve more than 75% 3 months product stability (Feldman EG.Consistency in stability testing[J] .J Pharm sci, 1979,68:1), product no layering or deposited phenomenon in centrifugal process according to the observation, the existing picture of no breakdown of emulsion behind the freezing and high temperature, by above-mentioned condition preservation after three months steady statue good, be good ointment dosage form.
Embodiment 2:
Oleum sesami, water mixed system, sodium alginate powder, glutaraldehyde, class of department system:
In Oleum sesami, water mixed system, the class of emulsifying agent department that adds finished product ointment 1%wt, sodium alginate is dissolved in the profit mixed system, the ratio that addition accounts for finished product ointment weight is not less than the solution that 0.5%wt is not more than 5%wt, stir more than 30 minutes being not less than under 500 revolutions per seconds the rotating speed, drip glutaraldehyde solution at last, the weight ratio that the amount that drips glutaraldehyde accounts for finished product ointment is not less than 0.5% and is not more than 8%, promptly makes ointment formulation.Denseness and the viscosity (η c) of finding emulsifying ointment after testing are not less than 3.18mPa.s, and percentage of water loss detects finds that the percentage of water loss of emulsifying ointment 5h is not higher than 6.73%wt.With emulsifying ointment and co-culture of cells, cell growth state is good, and MTT detects and finds that seven days rates of increase of cell reach 98%.Emulsifying ointment Random Graph is distributed on volunteer's human body skin, washes with water behind the 1h and remove, the result shows that the emulsifying ointment is easy to coating, is easy to eluting, and human body skin does not have rubescent, plays phenomenons such as rash.Ointment is placed the centrifugal 30min of rotating speed of 30 degree isoperibol 2500r/min, and whether microexamination has layering or precipitation; Respectively at-15 ℃ of refrigerator 24h, 55 ℃ of calorstat 6h, whether observe has demulsifying phenomenon, 37～40 ℃ of temperature, humidity is preserved 3 months product stability more than 75%, no breakdown of emulsion now looks like behind product no layering or the deposited phenomenon in centrifugal process according to the observation, freezing and high temperature, it is good to preserve after three months steady statue by above-mentioned condition, is good ointment dosage form.
Embodiment 3:
Liquid paraffin, water mixed system, the potassium alginate powder, chitosan, the AOT system:
In liquid paraffin, water mixed system, the emulsifying agent AOT that adds finished product ointment 3%wt, sodium alginate is dissolved in the profit mixed system, the ratio that addition accounts for finished product ointment weight is not less than the solution that 0.5%wt is not more than 5%wt, stir more than 30 minutes being not less than under 500 revolutions per seconds the rotating speed, drip chitosan solution at last, the weight ratio that the amount that drips chitosan accounts for finished product ointment is not less than 0.5% and is not more than 10%,, promptly make ointment formulation.Denseness and the viscosity (η c) of finding emulsifying ointment after testing are not less than 3.18mPa.s, and percentage of water loss detects finds that the percentage of water loss of emulsifying ointment 5h is not higher than 6.73%wt.With emulsifying ointment and co-culture of cells, cell growth state is good, and MTT detects and finds that seven days rates of increase of cell reach 98%.Emulsifying ointment Random Graph is distributed on volunteer's human body skin, washes with water behind the 1h and remove, the result shows that the emulsifying ointment is easy to coating, is easy to eluting, and human body skin does not have rubescent, plays phenomenons such as rash.Ointment is placed the centrifugal 30min of rotating speed of 30 degree isoperibol 2500r/min, and whether microexamination has layering or precipitation; Respectively at-15 ℃ of refrigerator 24h, 55 ℃ of calorstat 6h, whether observe has demulsifying phenomenon, 37～40 ℃ of temperature, humidity is preserved 3 months product stability more than 75%, no breakdown of emulsion now looks like behind product no layering or the deposited phenomenon in centrifugal process according to the observation, freezing and high temperature, it is good to preserve after three months steady statue by above-mentioned condition, is good ointment dosage form.
Two, the practical application (annotate: percentage ratio in system be mass percent W/W%) of ointment in medicine processing
One class oil, the blended medicine stock solution of water are made ointment with the ointment production technology of the present invention's design, oiliness base and aqueous base are respectively 45%wt and 53%wt residue and are Powdered profit insoluble drugs in the ingredient, in mixed liquor, drip the tween of ointment quality 5%wt, ointment quality 3%wt is dissolved in the aqueous phase of profit mixed system to the sodium alginate of 5%wt, evenly stir, rotating speed is greater than 500 revolutions per seconds, drip the alginic acid cross-linking agent, continuation is stirred more than half an hour with same speed, stops after half an hour stirring.Denseness and the viscosity (η c) of finding emulsifying ointment after testing are not less than 3.18mPa.s, and percentage of water loss detects finds that the percentage of water loss of emulsifying ointment 5h is not higher than 6.73%wt.With emulsifying ointment and co-culture of cells, cell growth state is good, and MTT detects and finds that seven days rates of increase of cell reach 98%.Emulsifying ointment Random Graph is distributed on volunteer's human body skin, washes with water behind the 1h and remove, the result shows that the emulsifying ointment is easy to coating, is easy to eluting, and human body skin does not have rubescent, plays phenomenons such as rash.Ointment places the centrifugal 30min of rotating speed of 30 degree isoperibol 2500r/min, and whether microexamination has layering or precipitation; Respectively at-15 ℃ of refrigerator 24h, 55 ℃ of calorstat 6h, whether observe has demulsifying phenomenon, 37～40 ℃ of temperature, humidity is preserved more than 75% and was observed product stability in 3 months, and no breakdown of emulsion now looks like behind product no layering or the deposited phenomenon in centrifugal process according to the observation, freezing and high temperature, it is good to preserve after three months steady statue by above-mentioned condition, is good ointment dosage form.
Three, human experimentation
Emulsifying ointment Random Graph is distributed on volunteer's human body skin, washes with water behind the 1h and remove, the result shows that the emulsifying ointment is easy to coating, is easy to eluting, and human body skin does not have rubescent, plays phenomenons such as rash.The result as shown in Table 1
Table 1 ointment is to the influence of human body skin
| Coating | Eluting | Rubescent | Play rash | Aggregate performance | |
| Volunteer's first | Easily be colourless after the mastic coating | Easily | Do not have | Do not have | Skin is wetting state |
| Volunteer's second | Easily be colourless after the mastic coating | Easily | Do not have | Do not have | Skin is wetting state |
| The volunteer third | Easily be colourless after the mastic coating | Easily | Do not have | Do not have | Skin is wetting state |
| Volunteer's fourth | Easily be colourless after the mastic coating | Easily | Do not have | Do not have | Skin is wetting state |
Claims (9)
1. oil-in-water type ointment, it is characterized in that this ointment comprises alginic acid and salt, emulsifying agent, cross-linking agent, oiliness base and aqueous base, wherein the oiliness base accounts for the mass ratio of oil-in-water type ointment between 10%-85%, alginic acid and salt thereof shared mass ratio in oil-in-water type ointment is not more than 7%, emulsifying agent shared mass ratio in oil-in-water type ointment is not less than 1% and is not higher than 30%, cross-linking agent is not less than with the ratio of the adding quality of alginic acid and salt thereof in oil-in-water type ointment and is not higher than 5: 1 at 1: 10, remains to be the aqueous base.
2. oil-in-water type ointment according to claim 1, it is characterized in that described oiliness base is vegetable and animals oils or vegetable oil, described vegetable and animals oils is: a kind of or any several mixture in paraffin, liquid paraffin, white vaseline, lanoline, hexadecanol, octadecanol, the glycerol etc.; Described vegetable oil is Oleum Ricini, Oleum Glycines, Oleum sesami or Cera Flava.
3. oil-in-water type ointment according to claim 1 is characterized in that described aqueous base is the polar solvent that is insoluble to oil.
4. oil-in-water type ointment according to claim 1 is characterized in that described alginic acid and salt thereof, is one or more mixed-powders in potassium alginate, sodium alginate or the alginic acid.
5. oil-in-water type ointment according to claim 1 is characterized in that described emulsifying agent is the serial emulsifying agent of class of department, twain series emulsifier or AOT, and the HLB value of used emulsifying agent is between 4-23.
6. oil-in-water type ointment according to claim 1 is characterized in that described cross-linking agent is bivalent metal ion saline solution, chitosan or glutaraldehyde.
7. oil-in-water type ointment according to claim 3 is characterized in that the described polar solvent that is insoluble to oil is a distilled water.
8. oil-in-water type ointment according to claim 6 is characterized in that described bivalent metal ion saline solution is: Ca
2+, Pb
2+, Cu
2+, Cd
2+, Co
2+, Ni
2+, Zn
2+Or Mn
2+Saline solution.
9. according to any described oil-in-water type ointment of claim 1-8, it is characterized in that the denseness of ointment and viscosity are not less than 3.18mPa.s, the percentage of water loss of emulsifying ointment 5h is not higher than 6.73%.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102410572A CN101947200B (en) | 2010-07-30 | 2010-07-30 | Emulsion type ointment |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102410572A CN101947200B (en) | 2010-07-30 | 2010-07-30 | Emulsion type ointment |
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| CN101947200A true CN101947200A (en) | 2011-01-19 |
| CN101947200B CN101947200B (en) | 2013-04-03 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1249930A (en) * | 1998-10-07 | 2000-04-12 | 江苏省药物研究所 | Diclofenac potassium gel and ointment and the preparation thereof |
| CN1939319A (en) * | 2005-09-28 | 2007-04-04 | 江苏正大天晴药业股份有限公司 | Isoglycyrrhiza acid magnesium externally-applied preparation, its making method and usage |
| CN100998556A (en) * | 2006-12-30 | 2007-07-18 | 东南大学 | Ointment preparation and its preparing method |
-
2010
- 2010-07-30 CN CN2010102410572A patent/CN101947200B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1249930A (en) * | 1998-10-07 | 2000-04-12 | 江苏省药物研究所 | Diclofenac potassium gel and ointment and the preparation thereof |
| CN1939319A (en) * | 2005-09-28 | 2007-04-04 | 江苏正大天晴药业股份有限公司 | Isoglycyrrhiza acid magnesium externally-applied preparation, its making method and usage |
| CN100998556A (en) * | 2006-12-30 | 2007-07-18 | 东南大学 | Ointment preparation and its preparing method |
Non-Patent Citations (2)
| Title |
|---|
| 何东保等: "壳聚糖－海藻酸钠协同相互作用及其凝胶化的研究", 《武汉大学学报（理学版）》 * |
| 高健等: "交联海藻酸钠微囊的制备及其在药物缓释中的应用", 《连云港师范高等专科学校学报》 * |
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