CN103735494B - External antipruritic ointment for treating mosquito bite and preparation method of external antipruritic ointment - Google Patents
External antipruritic ointment for treating mosquito bite and preparation method of external antipruritic ointment Download PDFInfo
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- CN103735494B CN103735494B CN201410015289.4A CN201410015289A CN103735494B CN 103735494 B CN103735494 B CN 103735494B CN 201410015289 A CN201410015289 A CN 201410015289A CN 103735494 B CN103735494 B CN 103735494B
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Abstract
The invention discloses external antipruritic ointment for treating mosquito bite and a preparation method of the external antipruritic ointment. The external antipruritic ointment comprises A, B, C, D, E and F components, wherein A is an active ingredient, namely, 11.32 to 18.87 parts of 25.0 to 28.0% (g/g) ammonia solution; B is 3.0 to 8.0 parts of polysorbate 80; C is 3.0 to 8.0 parts of glycine; D is 1.5 to 3.0 parts of dimethicone; E is 1.5 to 3.0 parts of liquid paraffin; F is 59.13 to 79.68 parts of purified water. The preparation method comprises the following steps of by taking ammonium hydroxide as the active ingredient, dissolving the active ingredient and pharmaceutic adjuvant; filtering through a filter membrane; disinfecting; sterilizing at high temperature; homogenizing at low speed; homogenizing at high speed; agitating; cooling; cooling; and performing other processes to obtain the external antipruritic ointment. The external antipruritic ointment is externally applied to skin and shows a good clinical effect on treatment of pain and pruritus of a lump caused by mosquito bite.
Description
Technical field
The present invention relates to a kind of lump external use anti pruritic emulsifiable paste causing sufferings symptom and preparation method thereof being used for the treatment of mosquito bite and producing, belong to medical art.
Background technology
Mosquito belongs to Insecta Diptera, is small-sized insecticide, and kind is a lot, and the known world has kind more than 3000, China has found that more than 300 plant, but energy disseminator animal diseases is not too many, mainly anopheles, culex, yellow-fever mosquito.Mosquito has elongated beak and foot, there is special vein and typically sting sucking mouth part, it is not only sucked blood and stabs the rest that skin hinders people, and can propagate the infectious disease such as filaricide, malaria, encephalitis, dengue fever, and therefore mosquito is one of harm humans the most serious healthy insecticide.Mosquito bite is autumn in summer warm moist commonly encountered diseases in season, bite rear many Dermal exposure position or directly contact site occur circular or oval, the grain of rice is large or the red papules of Semen Glycines size, papulovesicle or edematous erythema, erythra central authorities common pinhead-sized " bite mark ", and with violent pruritus, especially being night very.
As everyone knows, the temperature rises, and mosquito will harass the mankind, not only affects the sleep of people, but also the skin of bites humans, not only make people's sufferings, also may infect Other diseases.Mosquito bite can play bag, this mainly the saliva of skin to insect have anaphylaxis, some is all moved back to go down by a wheat harvesting period red packet serious after mosquito bite.For mosquito bite, present various folk prescription and medicine very many, folk prescription such as Aloe, zicao soft plaster etc. are not necessarily all effective to everyone.The medicine of common menthocamphorate, essential balm one class has alcoholic content, and the people being not suitable for skin sensitivity uses.As for the medicine of hormones, antipruritic effect can clearly, but child needs to be cautious use of.
At present, generally by after mosquito bite, redness is alleviated with mosquito acidic toxins in available soap or the rear local of sodium bicarbonate dilution, clean with such as green ointment, floral water, WUJI GAO, Calamine Lotion etc. the place of biting antipruritic simultaneously, but above effect is not ideal, be difficult to the effect reaching rapid repellent antipruritic.
Summary of the invention
For the deficiencies in the prior art, a kind of lump for the treatment of mosquito bite generation is the object of the present invention is to provide to cause the external use anti pruritic emulsifiable paste of sufferings symptom; The present invention also provides the preparation method of this ointment.
Term explanation
Purified water: the water of the hyoscine that drinking water obtains through the way of distillation, ion exchange, hyperfiltration or other suitable methods.
Relative density: according to Chinese Pharmacopoeia version in 2010 two annex VI A, refer to the ratio of the density of material and the density of standard substance, standard substance is water.
Ammonia: be colourless supernatant liquid, have the abnormal smells from the patient of intense stimulus, volatile; Aobvious alkaline reaction, this product can mix arbitrarily with water or ethanol, and Chinese Pharmacopoeia version in 2010 two, medicinal ammonia is containing ammonia (NH
3) should be 25.0 ~ 28.0% (g/g).
Emulsifiable paste: mean medicine dissolution or be scattered in emulsion type substrate the uniform semi-solid external preparation formed.
Technical scheme of the present invention is as follows:
Treat an external use anti pruritic emulsifiable paste for mosquito bite, composed as follows, be mass parts:
A: active component: medicinal ammonia 11.32 ~ 18.87 parts (folding of mass percent concentration 25.0 ~ 28.0% (g/g)
NH
33.0 ~ 5.0 parts),
According to the present invention, preferably, a kind of external use anti pruritic emulsifiable paste for the treatment of mosquito bite, composed as follows, be mass parts:
A: active component: medicinal ammonia 11.32 ~ 15.09 parts (the folding NH of mass percent concentration 25.0 ~ 28.0% (g/g)
33.0 ~ 4.0 parts),
According to the present invention, further preferably, a kind of external use anti pruritic emulsifiable paste for the treatment of mosquito bite, composed as follows, be mass parts:
A: active component: medicinal ammonia 13.2 parts (the folding NH of mass percent concentration 25.0 ~ 28.0% (g/g)
33.5 parts),
Or,
A: active component: medicinal ammonia 11.32 parts (the folding NH of mass percent concentration 25.0 ~ 28.0% (g/g)
33.0 parts),
Or,
A: active component: medicinal ammonia 15.09 parts (the folding NH of mass percent concentration 25.0 ~ 28.0% (g/g)
34.0 parts),
What raw material of the present invention was not particularly illustrated be market can purchase.
The preparation method of the external use anti pruritic emulsifiable paste for the treatment of mosquito bite of the present invention, step is as follows:
(1) each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3), after aqueous phase step (1) obtained is degerming with 0.2 ~ 0.3 μm of membrane filtration, the tinning of gained aqueous phase deposited, room temperature is for subsequent use;
(4) by oil phase obtained for step (2) sterilizing 30 ~ 40 minutes under 121 ~ 125 DEG C of conditions, the oil phase tinning of gained deposited, room temperature is for subsequent use;
(5) oil phase for subsequent use for step (4) is joined in the aqueous phase liquid for subsequent use of step (3), stir, the suction of gained mixture is sheared in tank; Under normal temperature condition, open cutter low speed 1000 ~ 1750r/min and shear 8 ~ 10 minutes, then 2500 ~ 2880r/min shears 4 ~ 5 minutes at a high speed; Close cutter, open and stir, continue stirring 5 ~ 10 minutes, and then stir under speed of agitator is 30 ~ 50r/min under rotating speed is 60 ~ 90r/min, stop stirring when being cooled to 30 ~ 35 DEG C, Quan Jian, packaging, to obtain final product.
According to the present invention, preferably,
Above-mentioned steps (1), (2) (3), (4) are all implemented under 300,000 grades of clean internal conditions;
Above-mentioned steps (5) is implemented under 100,000 grades of clean internal conditions;
The oil phase that the aqueous phase that above-mentioned steps (3) obtains, step (4) obtain all is delivered in the tank in 100,000 grades of clean areas and deposits.
According to the present invention, further preferably, the preparation method of the external use anti pruritic emulsifiable paste of described treatment mosquito bite, step is as follows:
(1) in 300,000 grades of clean areas, each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) in 300,000 grades of clean areas, take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3) in 300,000 grades of clean areas, after aqueous phase step (1) obtained is degerming with 0.2 ~ 0.3 μm of membrane filtration, by gained aqueous phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(4) in 300,000 grades of clean areas, by oil phase obtained for step (2) sterilizing 30 minutes under 121 ~ 125 DEG C of conditions, by gained oil phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(5) under 100,000 grades of conditions, oil phase for subsequent use for step (4) is joined in the aqueous phase liquid of step (3), stir, the suction of gained mixture is sheared in tank; Under room temperature temperature conditions, open cutter low speed 1000 ~ 1250r/min and shear 8 ~ 10 minutes, then 2500 ~ 2800r/min shears 4 ~ 5 minutes at a high speed; Close cutter, open and stir, continue stirring 5 ~ 8 minutes, and then stir under speed of agitator is 30 ~ 50r/min under rotating speed is 60 ~ 80r/min, stop stirring when being cooled to 30 ~ 35 DEG C, Quan Jian, packaging, to obtain final product.
According to the present invention, more preferably, the preparation method of the external use anti pruritic emulsifiable paste of described treatment mosquito bite, step is as follows:
(1) in 300,000 grades of clean areas, each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) in 300,000 grades of clean areas, take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3) in 300,000 grades of clean areas, after aqueous phase step (1) obtained is degerming with 0.3 μm of membrane filtration, by gained aqueous phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(4) in 300,000 grades of clean areas, by oil phase obtained for step (2) sterilizing 30 minutes under 121 ~ 125 DEG C of conditions, by gained oil phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(5) under 100,000 grades of conditions, oil phase for subsequent use for step (4) is joined in the aqueous phase liquid of step (3), stir, the suction of gained mixture is sheared in tank; Under room temperature temperature conditions, open cutter low speed 1250r/min and shear 10 minutes, then high speed 2800r/min shears 5 minutes; Close cutter, open and stir, continue stirring 8 minutes, and then stir under speed of agitator is 50r/min under rotating speed is 80r/min, stop stirring when being cooled to 35 DEG C, Quan Jian, packaging, to obtain final product.
The present invention is preferred, in above preparation method, and all pipelines for mass transport, and the steam that the storage tank depositing material passes into 3kg pressure all in advance carries out moist heat sterilization process 30 ~ 60min.
With regard to preparation method, be more than the preferred method of the present invention, but be not limited thereto.The knowledge that those skilled in the art knows according to it, can suitably be adjusted.The lump that the above treatment mosquito bite produces causes and to be not particularly limited in the external use anti pruritic cream preparation method of sufferings symptom, can refer to prior art.
Cream preparation of the present invention adopts ammonia to be effective ingredient, according to the physicochemical property of each composition of invention formulation supplementary material, if all adopt non-heating power sterilizing methods, as Filtration, because oil phase substrate is sticky, is difficult to filter.Through considering the feature of this preparation, the present invention adopts high-temperature sterilizing process to carry out sterilizing to the oil phase of pharmaceutical adjunct especially, and selects Filtration sterilizing to aqueous phase, to ensure that this preparation had both met state-promulgated pharmacopoeia requirement, can reach again the object of sterilizing.
The lump that treatment mosquito bite of the present invention produces causes the external use anti pruritic emulsifiable paste of sufferings symptom to have the following advantages:
1. ointment forming of the present invention, uniform color, be easy to get from raw material sources and economic angle raw material, preparation cost is low.
2. add odor mask glycine in invention formulation and preferred consumption, ammonia complexing in glycine and ammonia, slow releasing ammonia in skin surface, avoid irritating abnormal smells from the patient of ammonia on the one hand, persistence slow releasing ammonia is to reach the object extending drug effect on the other hand, so without ammonia odor, user is more taken like a shot.
3. ointment is by dermal application, in ammonia being infiltrated to be organized by mosquito bite, plays antibacterial, antiviral, repellent antipruritic and accelerates the effects such as organized renewing function.
External use anti pruritic emulsifiable paste of the present invention should have no irritating odor, and is easily accepted by patient, and therefore having no irritating odor is an important inspection target.The present invention makes odor mask with glycine, and screens its consumption, with abnormal smells from the patient, outward appearance, is shaped to standard.The results are shown in Table 1.
Table 1 odor mask consumption the selection result (unit: g)
| Prescription component | 1 | 2 | 3 | 4 | 5 | 6 |
| Ammonia (26.5%) | 13.2 | 13.2 | 13.2 | 13.2 | 13.2 | 13.2 |
| Polyoxyethylene sorbitan monoleate | 4.7 | 4.7 | 4.7 | 4.7 | 4.7 | 4.7 |
| Glycine | 0 | 1.7 | 2.7 | 3.7 | 4.7 | 5.7 |
| Dimethicone | 1.9 | 1.9 | 1.9 | 1.9 | 1.9 | 1.9 |
| Liquid paraffin | 1.9 | 1.9 | 1.9 | 1.9 | 1.9 | 1.9 |
| Purified water | 78.3 | 76.6 | 75.6 | 74.6 | 73.6 | 72.6 |
Prescription evaluation and result:
Prescription 1: appearance luster is even, and ammonia odor is obvious;
Prescription 2: appearance luster is even, and ammonia odor is more obvious;
Prescription 3: appearance luster is even, and ammonia odor is obvious;
Prescription 4: appearance luster is even, has a small amount of ammonia odor;
Prescription 5: appearance luster is even, without ammonia odor;
Prescription 6: appearance luster is even, without ammonia odor;
Comprehensive above prescription, result visual appearance difference is not obvious.Have ammonia odor in prescription 1,2,3,4, prescription 5,6, without ammonia odor, is applicable to the requirement of prescription, considers supplementary product consumption in preparation, determines the preferred consumption selecting the consumption of glycine in prescription 5 as odor mask in invention formulation.
Add odor mask glycine in invention formulation, avoid irritating abnormal smells from the patient of ammonia on the one hand, persistence slow releasing ammonia is to reach the object extending drug effect on the other hand, and tests its dissolution;
The preparation of need testing solution: each 2g of test external use anti pruritic emulsifiable paste of Example 1 ~ 3, according to " Chinese Pharmacopoeia 2010 version two " (annex X C) second method dissolution method, with the 1000ml water after degassed process for dissolution medium, rotating speed is 75 turns ± 5 revs/min, operate in accordance with the law, respectively at 5min, 10min, 20min, 30min, 45min, sampling 20ml, filter, get subsequent filtrate as need testing solution; With the content of sulphuric acid volumetric solution (0.5mol/L) titration ammonia.
External use anti pruritic emulsifiable paste Dissolution Rate Testing shows: the persistence slow releasing in 45min of the ammonia composition in external use anti pruritic emulsifiable paste.In table 2.
Ammonia composition in table 2 external use anti pruritic emulsifiable paste
Result shows: the dissolution of external use anti pruritic emulsifiable paste embodiment 1 ~ 3 is all more than 80%.With the time (minute), curve is done to its stripping quantity (%), obtain the stripping curve of each sample, see accompanying drawing 1 ~ 3.
External use anti pruritic emulsifiable paste quality standard of the present invention is following but be not limited thereto.
External use anti pruritic emulsifiable paste medicine quality standard
This product is containing ammonia (NH
3) should be 3.0 ~ 4.0% (g/g).
[shape] this product is milky ointment.
It is a small amount of that [discriminating] gets this product, separately dips hydrochloric acid with Glass rod, hold nearly this product, produces the smog of white.
[inspection]
Dissolubility: get this product 1g, the 20ml that adds water stirs, and should be able to dissolve completely.
PH value: get this product 1g and be dissolved in 20ml distilled water, at mensuration pH value, should between 9.5 ~ 11.
Viscosity: according to " Chinese Pharmacopoeia version in 2010 two annex VI G second methods ", adopt NDJ-1 type Rotary Viscosimeter, with No. 4 rotors, rotating speed is 6 turns per minute, measures in accordance with the law, and the dynamic viscosity 25 DEG C time should be 10 ~ 15pa ﹒ s.
Granularity: check according to granularity and particle size distribution method " Chinese Pharmacopoeia version annex Ⅸ E first method in 2010 ", all must not detect the particle being greater than 180 μm.
Other: other requirements under this product should meet " Chinese Pharmacopoeia version annex I F in 2010 " emulsifiable paste item.
[assay] is got this product and is about 2g, is equipped with water 25ml and in the tool plug conical flask of weighed weight, and accurate amount is fixed, and the red indicator solution of methylate 2, with sulphuric acid volumetric solution (0.5mol/L) titration.Every 1ml sulphuric acid volumetric solution (0.5mol/L) is equivalent to the NH of 17.03mg
3.
The lump that treatment mosquito bite of the present invention produces causes the external use anti pruritic emulsifiable paste of sufferings symptom, adopt ammonia to be the effective ingredient of medicine of the present invention, with pharmaceutic adjuvant by dissolving, the technique such as membrane filtration is degerming, high temperature sterilize, low speed homogenizing, high speed homogenization, stirring, cooling, fill makes medicament.Through external preparation for skin drug administration, sufferings symptom is caused to have good clinical effect to the lump that mosquito bite produces.Effect experimental specifically will be explained in an embodiment.
Accompanying drawing explanation
Fig. 1 is the external use anti pruritic emulsifiable paste stripping curve of embodiment 1; Vertical coordinate: the stripping quantity (%) of ammonia, abscissa: time (min);
Fig. 2 is the external use anti pruritic emulsifiable paste stripping curve of embodiment 2; Vertical coordinate: the stripping quantity (%) of ammonia, abscissa: time (min);
Fig. 3 is the external use anti pruritic emulsifiable paste stripping curve of embodiment 3; Vertical coordinate: the stripping quantity (%) of ammonia, abscissa: time (min).
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described further, but be not limited thereto.
Embodiment 1 ~ 3 supplementary material illustrated in table 3:
Table 3 embodiment 1 ~ 3 supplementary material is originated
| Supplementary material title | Manufacturing enterprise | Operative norm |
| Ammonia | Nanjing Chemistry Reagent Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Polyoxyethylene sorbitan monoleate | Nanjing WeiEr chemical engineering Co., Ltd | Chinese Pharmacopoeia 2010 editions two |
| Glycine | Jinzhou Ji Rong aminoacid company limited | Chinese Pharmacopoeia 2010 editions two |
| Dimethicone | Zi Gong Hong He Pharmaceutical Co | Chinese Pharmacopoeia 2010 editions two |
| Liquid paraffin | SINOPEC's Hangzhou Refinery | Chinese Pharmacopoeia 2010 editions two |
| Purified water | Shandong Sibangde Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
Equipment cutter used in the present invention etc. is the conventional equipment that this area uses.
Cutter: model ZJR-50L, Wuxi Xing De transmission Science and Technology Ltd. is on sale.
Embodiment 1, external use anti pruritic emulsifiable paste and preparation
Treat an external use anti pruritic emulsifiable paste for mosquito bite, composed as follows:
A: active component: medicinal ammonia 13.2 parts (the folding NH of mass percent concentration 25.0 ~ 28.0% (g/g)
33.5 parts),
Be prepared as follows and form:
(1) in 300,000 grades of clean areas, each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) in 300,000 grades of clean areas, take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3) in 300,000 grades of clean areas, after aqueous phase step (1) obtained is degerming with 0.3 μm of membrane filtration, deposit in the tank in gained water conveying to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(4) in 300,000 grades of clean areas, by oil phase obtained for step (2) sterilizing 30 minutes under 121 ~ 125 DEG C of conditions, be delivered to respectively in the tank in 100,000 grades of clean areas and deposit, room temperature is for subsequent use;
(5) under 100,000 grades of conditions, oil phase for subsequent use for step (4) is joined in the aqueous phase liquid of step (3), stir, the suction of gained mixture is sheared in tank; Under room temperature temperature conditions, open cutter low speed 1250r/min and shear 10 minutes, then high speed 2800r/min shears 5 minutes; Close cutter, open and stir, continue stirring 8 minutes, and then stir under speed of agitator is 50r/min under rotating speed is 80r/min, stop stirring when being cooled to 35 DEG C, Quan Jian, packaging, to obtain final product, test lot number 20100301; This product is containing ammonia (NH
3) be 3.5% (g/g).
Embodiment 2, external use anti pruritic emulsifiable paste and preparation
Treat an external use anti pruritic emulsifiable paste for mosquito bite, composed as follows:
A: active component: medicinal ammonia 15.09 parts (the folding NH of mass percent concentration 25.0 ~ 28.0% (g/g)
34.0 parts),
Be prepared as follows and form:
(1) in 300,000 grades of clean areas, each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) in 300,000 grades of clean areas, take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3) in 300,000 grades of clean areas, after aqueous phase step (1) obtained is degerming with 0.22 μm of membrane filtration, by gained aqueous phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(4) in 300,000 grades of clean areas, by oil phase obtained for step (2) sterilizing 30 minutes under 121 ~ 125 DEG C of conditions, by gained oil phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(5) under 100,000 grades of conditions, oil phase for subsequent use for step (4) is joined in the aqueous phase liquid of step (3), stir, the suction of gained mixture is sheared in tank; Under room temperature temperature conditions, open cutter low speed 1000r/min and shear 8 minutes, then high speed 2500r/min shears 4 minutes; Close cutter, open and stir, continue stirring 5 minutes, and then stir under speed of agitator is 30r/min under rotating speed is 60r/min, stop stirring when being cooled to 30 DEG C, Quan Jian, packaging, to obtain final product, test lot number 20100302; This product is containing ammonia (NH
3) be 4.0% (g/g).
Embodiment 3, external use anti pruritic emulsifiable paste and preparation
Treat an external use anti pruritic emulsifiable paste for mosquito bite, composed as follows:
A: active component: medicinal ammonia 11.32 parts (the folding NH of mass percent concentration 25.0 ~ 28.0% (g/g)
33.0 parts),
Be prepared as follows and form:
(1) in 300,000 grades of clean areas, each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) in 300,000 grades of clean areas, take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3) in 300,000 grades of clean areas, after aqueous phase step (1) obtained is degerming with 0.23 μm of membrane filtration, by gained aqueous phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(4) in 300,000 grades of clean areas, by oil phase obtained for step (2) sterilizing 30 minutes under 121 ~ 125 DEG C of conditions, by gained oil phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(5) under 100,000 grades of conditions, oil phase for subsequent use for step (4) is joined in the aqueous phase liquid of step (3), stir, the suction of gained mixture is sheared in tank; Under room temperature temperature conditions, open cutter low speed 1100r/min and shear 9 minutes, then high speed 2600r/min shears 5 minutes; Close cutter, open and stir, continue stirring 7 minutes, and then stir under speed of agitator is 40r/min under rotating speed is 70r/min, stop stirring when being cooled to 32 DEG C, Quan Jian, packaging, to obtain final product, test lot number 20100303; This product is containing ammonia (NH
3) be 3.0% (g/g).
Embodiment 4, external use anti pruritic emulsifiable paste rabbit Skin Irritation Test
1, test material
(1) medicine: external use anti pruritic emulsifiable paste, the external use anti pruritic emulsifiable paste (test lot number 20100301) of Example 1 is stand-by as test sample.
Excipient: by embodiment 1 preparation method, do not add excipient prepared by ammonia, stand-by.
(2) animal: select healthy rabbits 8, every body weight about 1.8 ~ 2.0kg, is provided by Shandong University's Experimental Animal Center.2, rabbit Skin Irritation Test
Get the rabbit 8 of healthy adult, ♀ ♂ half and half.The electricity consumption of back part of animal spinal column diamond wool is evaded hair in first 24 hours in administration by normal skin, and depilation area is 3 × 3cm2.Damaged skin depilating method is prepared with normal skin.Lose hair or feathers district with 75% ethanol partly sterilised, with aseptic syringe needle depilation local " # " shape cut, the degree of being with oozing of blood.Adopt consubstantiality left and right sides self-contrast method.75% ethanol partly sterilised is first used during the administration of normal skin group, take test sample and each 0.5g of excipient, be applied to rabbit right, depilation district, left side (administration area 3 × 3cm2) respectively, then cover with double gauze and one deck cellophane, then closed by fixture, fix.With the medicine of warm water cleaning application area after 4 hours.Each administration should continuously at same regional administration, and damaged skin group gives medicine with method.Administration every day 1 time, successive administration 7 days.Last administration to remove after tested material 1,24,48,72h observes and records irritant reaction situations such as smearing position erythema and edema, and the recovery situation of above-mentioned change and recovery time.Observation terminates rear air tap inserting method and puts to death 1/2 animal, ♀ ♂ half and half, is then fixed by institute's bark fetching skin tissue 4% neutral formalin solution, carries out histopathological examination after HE dyeing.Residue animal continues observation 14 days, again carries out histopathological examination if desired.According to table 4 to removal medicine 1h and observed and recorded erythema and edema etc. before administration again, and to erythema and edema scoring.Calculate and put each group of integral mean value each observing time, then calculated and observe every animal integrated value in the time limit, carry out stimulus intensity evaluation by table 5.
Table 4 skin wound repair standards of grading
| Irritant reaction | Score value |
| Erythema | |
| Without erythema | 0 |
| Slight erythema (visible reluctantly) | 1 |
| Moderate erythema (obviously visible) | 2 |
| Severe erythema | 3 |
| Aubergine erythema is formed to slight eschar | 4 |
| Edema | |
| Without edema | 0 |
| Mild edema (visible reluctantly) | 1 |
| Intermediate edema (obviously swelling) | 2 |
| Severe edema (cutaneous protuberance 1mm, profile is clear) | 3 |
| Severe edema (more than cutaneous protuberance 1mm also has expansion) | 4 |
| High total mark | 8 |
Table 5 skin irritation intensity evaluation
| Score value | Evaluate |
| 0～0.49 | Nonirritant |
| 0.5～2.99 | Slight zest |
| 3.0～5.99 | Moderate zest |
| 6.0～8.0 | Strong and stimulating |
Duration of test, rabbit general status is good, before each administration, medicine remove after 1h and last administration remove medicine after 1h, 24h, 48h and 72h and convalescent period observe and terminate rear observation medication local and have no the symptoms such as obvious erythema, edema, pigmentation, petechia, pachylosis or epidermatic atrophy, scoring score value is 0.
Pathologic finding is visible, and intact skin group medication side undertissue, epidermis, adnexal structure are complete, clear, have no congested degeneration, necrosis and inflammatory reaction, compare have no obvious difference with excipient control side; Control sides epidermis is complete, without congested and inflammatory cell infiltration etc.; Drawing materials and organize all visible epidermis injury, inflammatory reaction and exudate in damaged skin group medication side, compares have no notable difference with excipient control side.When may prepare with damaged skin caused by mechanical damage, infer with medicine irrelevant.The visible epidermis injury of damaged skin control sides, inflammatory cell infiltration and exudate.
Under this experimental condition, external use anti pruritic emulsifiable paste to rabbit skin histology without obvious stimulation effect.Identical experiment is done to embodiment 2,3, also can draw this conclusion.
Embodiment 5, external use anti pruritic emulsifiable paste Cavia porcellus Buehler test
1, test material
(1) medicine: the external use anti pruritic emulsifiable paste (test lot number 20100301) of Example 1 is as test sample, stand-by.Excipient: by embodiment 1 preparation method, do not add excipient prepared by ammonia, stand-by.
(2) animal: healthy male guinea pig 40, every body weight about 250 ~ 300g, is provided by Shandong University's Experimental Animal Center.
2, Cavia porcellus Buehler tests
Get healthy male guinea pig 40, by body weight be divided into immediately excipient control group 10,2,4-dinitrochlorobenzene positive controls 10 and external use anti pruritic emulsifiable paste test sample group 20, point box is raised.Before medicine, Cavia porcellus left of spine rib abdominal part area about 3 × 3cm2 is scraped hair by 24h, positive controls takes 1%2,4-dinitrochlorobenzene 0.2g, excipient control group and test sample matched group take each 0.2g of external use anti pruritic emulsifiable paste respectively, be applied to district of losing hair or feathers on the left of Cavia porcellus, soft cellophane and 2.5 × 2.5cm2, bis-layers of gauze cover, then by fixture by drug blockage, fixing.With the medicine of warm water cleaning application area after 6 hours.7th day and the 14th day repeats sensitization 1 time, in the same fashion for 3 times.After this sensitization, depilation district, 14 days right sides first uses warm water cleaning administration place skin, then positive controls take 0.1%2,4-dinitrochlorobenzene 0.2g, excipient control group and test sample matched group take each 0.2g of external use anti pruritic emulsifiable paste respectively, be coated with and district of losing hair or feathers on the right side of Cavia porcellus, soft cellophane and 2.5 × 2.5cm2, bis-layers of gauze cover, then by fixture by drug blockage, fixing.6 hours with warm water cleaning smear zone medicine.Excite 24h, 48h after removing medicine to examine skin erythema, edema and other abnormal responses, by table 6 pair erythema and edema scoring, calculate irritated incidence rate.Anaphylaxis occurrence degree is judged according to table 7.
The standards of grading of table 6 skin allergy degree
| Dermoreaction intensity | Score value |
| Erythema | |
| Without erythema | 0 |
| Slight visible erythema | 1 |
| Moderate erythema | 2 |
| Severe erythema | 3 |
| Swollen property erythema | 4 |
| Edema | |
| Without edema | 0 |
| Mild edema | 1 |
| Intermediate edema | 2 |
| Severe edema | 3 |
| Maximum total mark | 7 |
Reaction meansigma methods=(erythema forms total score+edema and forms total score)/add up to number of animals.
Table 7 skin hypersensitivity evaluation criterion test sample group and excipient control
| Anaphylaxis incidence rate (%) | Classification | Anaphylaxis intensity |
| 0～8 | Ⅰ | Hyposensitiveness |
| 9～18 | Ⅱ | Slight sensitization |
| 29～64 | Ⅲ | Moderate sensitization |
| 65～80 | Ⅳ | Strong sensitization |
| 81～100 | Ⅴ | Extremely strong sensitization |
Number of animals/animal subject the number of anaphylaxis incidence rate=occur skin erythema or edema.
Duration of test, every day observes Cavia porcellus, and the external feature of Cavia porcellus, the mental status, the aspect such as behavioral activity and breathing show no obvious abnormalities.Before first time sensitization, last sensitization and weigh when exciting and calculate and often organize each body weight
each group compares with vehicle group, result no significant difference.The results are shown in Table 8.
The impact that table 8 external use anti pruritic emulsifiable paste medicine increases Cavia porcellus body weight
| Group | First sensitization | Last sensitization | Excite |
| Excipient control group | 341.3±5.0 | 375.2±5.0 | 408.8±5.4 |
| Positive controls | 343.9±12.0 | 377.5±11.9 | 410.9±12.0 |
| Test sample group | 345.4±18.6 | 379.0±18.4 | 412.3±18.5 |
Note: matched group n=10, test sample group n=20
All there is not erythema and edema at each time point in test sample group and excipient control group Cavia porcellus lasing region skin, reaction meansigma methods is 0, and anaphylaxis incidence rate is 0, and sensitivity response is negative.All there is erythema and edema removing medicine 24h, 48h in positive controls Cavia porcellus lasing region skin, reaction meansigma methods is respectively 1.7 and 1.8, and anaphylaxis incidence rate is 100%, in extremely strong sensitization.The results are shown in Table 9.
The initiatively skin allergy scoring of table 9 Cavia porcellus
Under this experiment condition, external use anti pruritic emulsifiable paste to Cavia porcellus without obviously initiatively sensitization of skin effect.Identical experiment is done to embodiment 2,3, also can draw this conclusion.
Embodiment 6, external use anti pruritic emulsifiable paste long-term stable experiment
According to " Chinese Pharmacopoeia 2010 version two " (annex XIX C) medicine stability test guideline, study on the stability has been carried out to the sample of embodiment 1, by " external use anti pruritic emulsifiable paste quality standard ", to its character, uniformity, acidity, related substance, tire, the project such as aseptic, lamination investigates.
Carry out long-term stable experiment by under the storage requirement of external use anti pruritic emulsifiable paste, investigate the stability features of external use anti pruritic emulsifiable paste in transport, preservation, use procedure, thus as determining the foundation of effect duration and storage requirement.
The external use anti pruritic emulsifiable paste sample of the embodiment 1 of polyethylene/aluminum/polyethylene compound ointment tube packaging will be adopted, be positioned over 25 ± 2 DEG C, the constant temperature of RH60 ± 10%, place 24 months in constant humidity cabinet, respectively at sampling in 0,3,6,9,12,18,24 month, detect every quality index, in table 10.
Table 10 external use anti pruritic emulsifiable paste long-term stable experiment result
Result: through the long-time stability investigation of 24 months, result display compared indices without significant change with 0 month, show that external use anti pruritic emulsifiable paste is good at temperature 25 ± 2 DEG C, humidity RH60 ± 10% condition stability inferior, under the terms and conditions of regulation, production, packaging, storage, transport all can not have a negative impact to the quality of this product, can ensure that clinical drug safety is effective.Identical experiment is done to embodiment 2,3, also can draw this conclusion.
Embodiment 7, external use anti pruritic cream for treating mosquito bite observation of curative effect
1, test material
(1) medicine: external use anti pruritic emulsifiable paste often props up weight 10.0g, the ammonia medicinal external emulsifiable paste prepared by embodiment 1; Test lot number 20100301.
(2) control drug: Momestasone furoate cream (Shanghai Schering Plough pharmaceutical Co. Ltd product: the accurate word H19991418 of traditional Chinese medicines) 0.1% (5g:5mg).
2, diagnostic criteria (1) all cases all have mosquito or other sting;
(2) the violent pruritus in rear local is bitten;
3, criterion of therapeutical effect is worked out according to (Chinese medical disease Standardization of diagnosis and curative effect);
Cure: whole body and local symptom disappear, red swelling of the skin, heat, bitterly, itch and disappear.
Take a turn for the better: whole body and local symptom alleviate, and swelling is disappeared.
Invalid: whole body and local symptom do not control, and even increase the weight of.
4, choose mosquito bite patient 100 example, be divided into treatment group and matched group at random.Treatment group 50 example, man 26 example, female 24 example; 2 ~ 40 years old age.Matched group 50 example, man 24 example, female 26 example; 4 ~ 38 years old age.Two groups of no significant difference (P ﹥ 0.05) in age, sex, the course of disease etc., have comparability.
5, therapeutic outcome: after mosquito bite skin, uniform application is in red swelling of the skin place, and dose adjusts according to Tumor size, 2 times/d.Therapeutic outcome sees the following form 11.
Table 11 liang group clinical drug comparitive study
| Group | Number of cases | Cure | Take a turn for the better | Invalid | Total effective rate % |
| Treatment group | 50 | 30 | 19 | 1 | 98 |
| Matched group | 50 | 28 | 21 | 1 | 98 |
Result: pass through controlled clinical trial, two groups of clinical efficacies are added up, according to healing, take a turn for the better, invalid, always have 100 patients and finally reach evaluation criteria, its total effective rate 98% for the treatment of group, its total effective rate of matched group 98%, two groups of comparing difference not statistically significants (P ﹥ 0.05), show that two kinds of clinical drug curative effects are consistent, the lump being the generation for the treatment of mosquito bite causes the active drug of sufferings symptom.Identical experiment is done to embodiment 2,3, also can draw this conclusion.
Claims (10)
1. treat an external use anti pruritic emulsifiable paste for mosquito bite, it is characterized in that, composed as follows, be mass parts:
2. external use anti pruritic emulsifiable paste as claimed in claim 1, is characterized in that, composed as follows, is mass parts:
3. external use anti pruritic emulsifiable paste as claimed in claim 1 or 2, is characterized in that, composed as follows, is mass parts:
4. external use anti pruritic emulsifiable paste as claimed in claim 1 or 2, is characterized in that, composed as follows, is mass parts:
5. external use anti pruritic emulsifiable paste as claimed in claim 1 or 2, is characterized in that, composed as follows, is mass parts:
6. the preparation method of the external use anti pruritic emulsifiable paste as described in as arbitrary in Claims 1 to 5, step is as follows:
(1) each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3), after aqueous phase step (1) obtained is degerming with 0.2 ~ 0.3 μm of membrane filtration, the tinning of gained aqueous phase deposited, room temperature is for subsequent use;
(4) by oil phase obtained for step (2) sterilizing 30 ~ 40 minutes under 121 ~ 125 DEG C of conditions, the oil phase tinning of gained deposited, room temperature is for subsequent use;
(5) oil phase for subsequent use for step (4) is joined in the aqueous phase liquid for subsequent use of step (3), stir, the suction of gained mixture is sheared in tank; Under normal temperature condition, open cutter low speed 1000 ~ 1750r/min and shear 8 ~ 10 minutes, then 2500 ~ 2880r/min shears 4 ~ 5 minutes at a high speed; Close cutter, open and stir, continue stirring 5 ~ 10 minutes, and then stir under speed of agitator is 30 ~ 50r/min under rotating speed is 60 ~ 90r/min, stop stirring when being cooled to 30 ~ 35 DEG C, Quan Jian, packaging, to obtain final product.
7. the preparation method of external use anti pruritic emulsifiable paste as claimed in claim 6, it is characterized in that, step (1), (2) (3), (4) are all implemented under 300,000 grades of clean internal conditions; Step (5) is implemented under 100,000 grades of clean internal conditions; The oil phase that the aqueous phase that step (3) obtains, step (4) obtain all is delivered in the storage tank in 100,000 grades of clean areas and deposits.
8. the preparation method of external use anti pruritic emulsifiable paste as claimed in claim 6, step is as follows:
(1) in 300,000 grades of clean areas, each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) in 300,000 grades of clean areas, take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3) in 300,000 grades of clean areas, after aqueous phase step (1) obtained is degerming with 0.2 ~ 0.3 μm of membrane filtration, by gained aqueous phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(4) in 300,000 grades of clean areas, by oil phase obtained for step (2) sterilizing 30 minutes under 121 ~ 125 DEG C of conditions, by gained oil phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(5) under 100,000 grades of conditions, oil phase for subsequent use for step (4) is joined in the aqueous phase liquid of step (3), stir, the suction of gained mixture is sheared in tank; Under room temperature temperature conditions, open cutter low speed 1000 ~ 1250r/min and shear 8 ~ 10 minutes, then 2500 ~ 2800r/min shears 4 ~ 5 minutes at a high speed; Close cutter, open and stir, continue stirring 5 ~ 8 minutes, and then stir under speed of agitator is 30 ~ 50r/min under rotating speed is 60 ~ 80r/min, stop stirring when being cooled to 30 ~ 35 DEG C, Quan Jian, packaging, to obtain final product.
9. the preparation method of external use anti pruritic emulsifiable paste as claimed in claim 8, step is as follows:
(1) in 300,000 grades of clean areas, each component of A, B, C group is taken by proportioning, after adding the purified water stirring and dissolving of meltage, as aqueous phase;
(2) in 300,000 grades of clean areas, take each component of D, E group by proportioning, to mix and after stirring, as oil phase;
(3) in 300,000 grades of clean areas, after aqueous phase step (1) obtained is degerming with 0.3 μm of membrane filtration, by gained aqueous phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(4) in 300,000 grades of clean areas, by oil phase obtained for step (2) sterilizing 30 minutes under 121 ~ 125 DEG C of conditions, by gained oil phase by depositing in the storage tank in Cemented filling to 10 ten thousand grades of clean areas, room temperature is for subsequent use;
(5) under 100,000 grades of conditions, oil phase for subsequent use for step (4) is joined in the aqueous phase liquid of step (3), stir, the suction of gained mixture is sheared in tank; Under room temperature temperature conditions, open cutter low speed 1250r/min and shear 10 minutes, then high speed 2800r/min shears 5 minutes; Close cutter, open and stir, continue stirring 8 minutes, and then stir under speed of agitator is 50r/min under rotating speed is 80r/min, stop stirring when being cooled to 35 DEG C, Quan Jian, packaging, to obtain final product.
10. the preparation method of the external use anti pruritic emulsifiable paste as described in as arbitrary in claim 6 ~ 9, is characterized in that, all pipelines for mass transport, and the steam that the storage tank depositing material passes into 3kg pressure all in advance carries out moist heat sterilization process 30 ~ 60min.
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| EP1661545A1 (en) * | 2004-10-15 | 2006-05-31 | L'oreal | O/W-cream comprising a fatty acid |
| CN101422427A (en) * | 2005-09-28 | 2009-05-06 | 江苏正大天晴药业股份有限公司 | Magnesium isoglycyrrhizinate cream and preparation method and use thereof |
| CN103006689A (en) * | 2012-12-25 | 2013-04-03 | 长春普莱医药生物技术有限公司 | Antipruritic composition and application of same in preparation of antipruritics |
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| EP1661545A1 (en) * | 2004-10-15 | 2006-05-31 | L'oreal | O/W-cream comprising a fatty acid |
| CN101422427A (en) * | 2005-09-28 | 2009-05-06 | 江苏正大天晴药业股份有限公司 | Magnesium isoglycyrrhizinate cream and preparation method and use thereof |
| CN103006689A (en) * | 2012-12-25 | 2013-04-03 | 长春普莱医药生物技术有限公司 | Antipruritic composition and application of same in preparation of antipruritics |
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Denomination of invention: External antipruritic cream for treating mosquito bites and its preparation method Effective date of registration: 20230704 Granted publication date: 20150701 Pledgee: Postal Savings Bank of China Limited Laiyang sub branch Pledgor: LAIYANG SBOND PHARMACEUTICAL CO.,LTD. Registration number: Y2023980047332 |