WO2013155741A1

WO2013155741A1 - Liuweidihuang liquid pill

Info

Publication number: WO2013155741A1
Application number: PCT/CN2012/075345
Authority: WO
Inventors: 王凤越; 张艳侠
Original assignee: 江苏颐海药业有限责任公司
Priority date: 2012-04-16
Filing date: 2012-05-11
Publication date: 2013-10-24

Abstract

Disclosed is a Liuweidihuang liquid pill, which is obtained by preparing extracts of six traditional Chinese medicines as the raw material and carriers as matrix of the liquid pills together; the weight ratio thereof is 1 : 1 ~ 8; the six traditional Chinese medicines consist of Chinese Foxglove, Cornus officinalis, Cortex Moutan Radicis, Dioscorea opposita, Rhizoma Alismatis and Poria. The matrix of the liquid pills is polyethylene glycol with a weight average molecular weight of 6000 and a viscosity distribution of 13.6 ~ 14.5.

Description

Liuwei Dihuang Dropping Pills

Technical field

The invention relates to a traditional Chinese medicine preparation.

Background technique

Liu Wei Di Huang Wan It consists of radix rehmanniae, hawthorn, yam, peony bark, diarrhea and medlar. It can be seen from the compatibility of drugs. It is combined with tonifying kidney and tonifying liver and spleen, and mainly tonifying kidney and yin. The existing Liuwei Dihuang preparations include honey pills, water pills, concentrated pills, tablets, hard capsules, soft capsules, oral liquids, granules, dropping pills, etc. Among these preparations, the dropping pills have high bioavailability and rapid drug release. It has rapid market efficiency, small toxic and side effects, and is easy to carry and has a large market share.

CN1247241C Disclosed is a Liuwei Dihuang Dropping Pill, the matrix of which is selected from the group consisting of polyethylene glycol 1500-10000, stearic acid, sodium stearate, glycerin gelatin, glyceryl monostearate, shellac, polyoxyethylene monostearate Any one or more of a mixture of a fat, a polyether, a sodium carboxymethyl starch and the like, and the above-mentioned substrate and the hexamesmide raw material are used as a dropping pill preparation to disperse the drug in a molecular, colloidal or microcrystalline state. In the matrix, the total surface area of the drug is increased, and the matrix is hydrophilic, which has a wetting effect on the drug, and the drug can be quickly dissolved into microparticles or a solution, thereby accelerating the dissolution and absorption of the drug, thereby improving bioavailability. Degree, play an efficient and quick effect.

In addition, CN100358507C discloses a large-size Liuwei Dihuang Pill, the substrate is polyethylene glycol 1000, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 10000, polyethylene glycol 20000, division Pan 40, polyoxyl 40 stearate, poloxamer, sodium lauryl sulfate, stearic acid, sodium stearate, glycerin gelatin, shellac, and polyoxyl 40 stearate a mixture of ethylene glycol 4000, and a mixture of poloxamer and polyethylene glycol 4000, and a mixture of sodium carboxymethyl starch and polyethylene glycol 4000, and b - a mixture of cyclodextrin and polyethylene glycol 4000. The invention aims to reduce the number of pills to be taken for patient convenience.

However, the melting time of the above two kinds of dropping pills is dispersed between 5 and 60 minutes, which makes it difficult to accurately control the blood concentration at a specific time point, and makes the drug unable to effectively and efficiently exert pharmacological effects.

technical problem

CN1247241C and CN100358507C The dispersing time limit of Liuwei Dihuang Dropping Pill disclosed in the above is dispersed between 5 and 60 minutes, which makes it difficult to accurately control the blood concentration at a specific time point, and makes the drug unable to effectively and efficiently exert pharmacological effects.

Technical solution

The technical scheme adopted by the invention is as follows: Liuwei Dihuang Dropping Pill, which is composed of ripe land, hawthorn, peony bark, yam, diarrhea and cockroach 6 The extract of the traditional Chinese medicine is obtained as a raw material, and is prepared together with a carrier as a matrix of the dropping pills, and is characterized in that:

1) The weight ratio of the extract of the 6 Chinese herbal medicines to the substrate is 1 : 1 to 8 ;

2) The extract of the 6 Chinese herbal medicines is obtained by the method specified in the pharmacopoeia or ministerial standards;

3) The dropping pill matrix has a weight average molecular weight of 6000 and a viscosity distribution between 13.6 and 14.5. Polyethylene glycol, the polyethylene glycol having a molecular weight of 6000 is 40-60% by weight;

4) accurately weigh the extract and the substrate according to the above ratio, put it in a heating container to heat it, melt it, stir it evenly, and then put it into the dropping machine, 75 ° C ~ 100 ° C, drip into the condensation agent of 30 ° C ~ -8 ° C, take out the dropping pills, wash and dry to obtain. .

The study found that the same PEG6000 (that is, polyethylene glycol with a weight average molecular weight of 6000) because it is PEG1 The mixture of ~ PEG + ∞ has a normal distribution. Among them, the PEG with a molecular weight of 6000 has the largest content, generally about 5%. The molecular weight of the invention is 6000. The polyethylene glycol has a weight content of 40 to 60% of PEG6000 (that is, polyethylene glycol having a weight average molecular weight of 6000), and the viscosity of the polyethylene glycol is between 13.6 and 14.5. The degree of polymerization is the highest, and as a matrix of dropping pills, a dropping pill having a high roundness, a high hardness, and a melting time controlled between 5 and 15 minutes can be obtained.

In a preferred embodiment of the present invention, the extract of the 6-flavored traditional Chinese medicine is a powder, and is obtained by the following method: taking the rehmannia glutinous by weight ratio 1408 servings, 528 servings of peony, 704 of yam, 704 of hawthorn, 528 of diarrhea and 528 of medlar, the above six flavors, taking 茯苓 110 The granules are pulverized into fine powder, and the remaining part of the sieve is decocted with the remaining mash for three times, each time for about 30 minutes, filtered, and the filtrate is combined and concentrated to a thick paste; the hawthorn is added with ethanol to reflux twice, each time 1 Hour, filtered, the dregs are reserved, the filtrate is recovered from ethanol, concentrated to a thick paste; the peony bar is steam distilled, and 1 mol/L is added to the collected distillate. The hydrochloric acid solution is crystallized, filtered, washed with water, dried at low temperature, and ground into fine powder; distilled aqueous solution and peony bark, hawthorn dregs and rehmannia root, yam and diarrhea are boiled three times, each time 1 Hour, filtered, combined filtrate, through the macroporous adsorption resin, with 70% Ethanol elution, collect the eluate, recover the ethanol, concentrate to a thick paste, add the above-mentioned glutinous cream, hawthorn thick paste and glutinous rice flour, mix, dry under reduced pressure, pulverize into fine powder, add the above-mentioned peony bark extract Powder, mix and get .

In a preferred embodiment of the present invention, the extract of the 6-flavored traditional Chinese medicine is a powder, and is obtained by the following method: taking the rehmannia glutinous by weight ratio 1408 servings, 528 pieces of peony, 704 pieces of yam, 704 pieces of hawthorn, 528 parts of Alisma and 528 parts of medlar, above six flavors, taking 茯苓 350 The granules are pulverized into fine powder; the hawthorn and ethanol are refluxed and extracted twice, each time for 1 hour, filtered, and the dregs are reserved. The filtrate is recovered from ethanol and concentrated to a thick paste; the peony bark is distilled by steam, and the distillate is added to 1 mol/L. The hydrochloric acid solution is crystallized and used; the distilled aqueous solution and the peony bark residue, the hawthorn dregs, the remaining barium, and the rehmannia root, the yam and the diarrhea are boiled three times, each time 1 After the hour, filter, combine the filtrate, concentrate to a thick paste; add the above-mentioned fine powder and hawthorn thick paste, mix, dry at low temperature, pulverize into fine powder, add the above-mentioned peony bark extract, and mix and obtain.

In a preferred embodiment of the invention, the 6 The extract of Chinese herbal medicine consists of extract powder and volatile oil of peony bark, and is obtained by the following method: 1408 parts of Rehmannia glutinosa, 528 pieces of peony skin, 704 parts of yam, Hawthorn 704. 528 parts of Alisma 528 and 528 parts of medlar, the above six flavors, steamed peony peel extract volatile oil, obtain volatile oil of peony bark, and extract the aqueous solution after 8 hours of steaming; 70% ethanol is refluxed and extracted twice, each time for 2 hours, the extract is combined, filtered, and the filtrate is ready for use; Rehmannia glutinosa, yam, and diarrhea are boiled twice with water, and the first time added 8 times the amount of water to cook. 2 hours, the second time with 6 times the amount of water to cook for 1 hour, combine and decoction, filtered, the filtrate is combined with the above distilled aqueous solution, concentrated under reduced pressure to a relative density of 1.15 ~1.20 clear paste, let cool, add ethanol to make the alcohol content up to 70%, stir well, let stand for 48 hours, take the supernatant and the above extract of hawthorn, decompression The ethanol is recovered to a non-alcoholic taste, and it is prepared. After boiling water, it is immersed twice at 80 °C, and each time 6 times of water is added, and the mixture is immersed for 1.5 hours, the leaching solution is combined, filtered, and the filtrate is concentrated under reduced pressure. The paste with a relative density of 1.15 to 1.20 (50 ° C) is combined with the above-mentioned preparation liquid, and concentrated to a thick paste having a relative density of 1.30 (50 ° C), and decompressed. Dry and pulverize into fine powder to obtain an extract powder.

Of course, the above 6 The extract powder of the traditional Chinese medicine is not limited to being obtained by using the above-mentioned several methods, and can also be obtained by the methods specified in other pharmacopoeia or Ministry of Health Ministry standards.

In a preferred embodiment of the invention, the substrate is preferably a polyethylene glycol 6000 having a viscosity of 14 (weight average molecular weight). This viscosity of polyethylene glycol 6000 has the highest degree of polymerization.

In a preferred embodiment of the present invention, the weight ratio of the extract powder of the 6-flavored Chinese medicine to the substrate is preferably 1:1.55.

In a preferred embodiment of the invention, the condensing agent is at least one of methyl silicone oil, liquid paraffin or vegetable oil.

The invention adopts PEG6000 with a molecular weight of 6000 and a weight content of 40 to 60% of polyethylene glycol. (ie, polyethylene glycol having a weight average molecular weight of 6000), and further Obtaining a high-density, high-hardness drop pill product, the obtained pill splitting time is controlled between 5 and 15 minutes, ensuring that the drug can be effectively and efficiently exerted pharmacologically.

Beneficial effect

The invention provides a Liuwei Dihuang Dropping Pill In order to solve the above problems existing in the prior art, the Liuwei Dihuang Dropping Pill not only has high roundness and high hardness, but also has a melting time controlled between 5 and 15 minutes, so that the medicine can be truly fast and efficient. Play a pharmacological role.

Embodiments of the invention

The invention is further described in the following examples, without any limitation of the invention.

实施例1 Example 1

1. Take 1408g of Rehmannia glutinosa, 528g of peony bark, 704g of yam, 704g of hawthorn, 528g of Alisma And 528 528g ;

2, take 茯苓 110g pulverized into fine powder, the remaining part of the sieve and the remaining 茯苓 add water to cook three times, each time 30 Minutes, filtered, combined filtrate, concentrated to a thick paste; Hawthorn plus ethanol reflux extraction twice, each time 1 Hour, filtered, the dregs are reserved, the filtrate is recovered from ethanol, concentrated to a thick paste; the peony bar is steam distilled, and 1 mol/L is added to the collected distillate. The hydrochloric acid solution is crystallized, filtered, washed with water, dried at low temperature, and ground into fine powder; distilled aqueous solution and peony bark, hawthorn dregs and rehmannia root, yam and diarrhea are boiled three times, each time 1 Hour, filtered, combined filtrate, through the macroporous adsorption resin, with 70% Ethanol elution, collect the eluate, recover the ethanol, concentrate to a thick paste, add the above-mentioned glutinous cream, hawthorn thick paste and glutinous rice flour, mix, dry under reduced pressure, pulverize into fine powder, add the above-mentioned peony bark extract Powder, mix and get the Liuwei Dihuang extract powder;

3. Add the extract of Liuwei Dihuang and the substrate in a ratio of 1:1, and mix well. The matrix is made of polyethylene glycol 6000. (weight average molecular weight), the viscosity of the polyethylene glycol is 13.6%, and the weight percentage of the polyethylene glycol having a molecular weight of 6000 is 40%;

4. Heat the mixture to melt and stir evenly;

5. Add the above materials to the dropping machine, keep the temperature at 75 ~ 80 °C, and then add 15 ~ 10 at the appropriate speed. In the methyl silicone oil of °C, remove it after shrinkage molding, remove the methyl silicone oil, and dry it.

实施例2 Example 2

2, take 茯苓 350g pulverized into fine powder; Hawthorn plus ethanol reflux extraction twice, each time 1 Hour, filtered, the dregs are reserved, the filtrate is recovered from ethanol, concentrated to a thick paste; the peony bark is distilled by steam, and the distillate is added to 1 mol/L. The hydrochloric acid solution is crystallized and used; the distilled aqueous solution and the peony bark residue, the hawthorn dregs, the remaining barium, and the rehmannia root, the yam and the diarrhea are boiled three times, each time 1 Hour, filter, combine the filtrate, concentrate to a thick paste; add the above-mentioned fine powder and hawthorn thick paste, mix, low-temperature drying, pulverize into fine powder, add the above-mentioned peony bark extract, and mix to obtain Liuwei Dihuang powder;

3. Add the extract of Liuwei Dihuang and the substrate in a ratio of 1:2, and mix well. The matrix is made of polyethylene glycol 6000. (weight average molecular weight), the viscosity of the polyethylene glycol is 14%, and the weight percentage of the polyethylene glycol having a molecular weight of 6000 is 50%;

4. Heat the mixture to melt and stir evenly;

5. Add the above materials to the dropping machine, keep the temperature at 80 ~ 85 °C, and then add 10 ~ 5 °C at the appropriate speed. In the methyl silicone oil, after being shrink-molded, it is taken out, the methyl silicone oil is removed, and it is dried.

实施例 3 Example 3

3. Add the extract of Liuwei Dihuang and the substrate according to the ratio of 1:1.55, and mix well. The matrix is made of polyethylene glycol 6000. (weight average molecular weight), the viscosity of the polyethylene glycol is 14.6%, and the weight percentage of the polyethylene glycol having a molecular weight of 6000 is 50%;

4. Heat the mixture to melt and stir evenly;

5, add the above materials to the dropping machine, keep the temperature at 85 ~ 90 ° C, and then drop 5 ~ 0 °C at the appropriate speed In the vegetable oil, remove it after shrinking, remove the vegetable oil, and dry it.

实施例 4 Example 4

2, the peony peel is distilled to extract the volatile oil, and the volatile oil of the peony bark is obtained, and the distillation is carried out for 8 hours. After the aqueous solution is collected, the hawthorn is added with 70% ethanol and refluxed twice, each time for 2 hours, the extract is combined, filtered, and the filtrate is ready for use; Rehmannia glutinosa, yam, and diarrhea are boiled with water. Two times, the first time adding 8 times the amount of water to cook for 2 hours, the second time adding 6 times the amount of water for 1 hour, combine and decoction, filtered, and the filtrate is combined with the above distilled aqueous solution, concentrated under reduced pressure. To the relative density of 1.15 ~ 1.20, let cool, add ethanol to make the alcohol content up to 70%, stir well, let stand for 48 hours, take the supernatant and the above extract of hawthorn Then, the ethanol is recovered under reduced pressure to a non-alcoholic taste. After boiling, the mixture is boiled at a temperature of 80 ° C, and then added twice with water, and immersed for 1.5 hours, combined with leachate, filtered, and filtered. Concentrate under reduced pressure to a relative density of 1.15 to 1.20 (50 ° C). Combine with the above preparation and concentrate to a relative density of 1.30 (50 ° C). The thick paste is dried under reduced pressure and pulverized into fine powder to obtain an extract powder; the volatile oil of the peony bark and the extract powder are taken up;

3. Add the extract of Liuwei Dihuang in the ratio of 1:8 (composed of volatile oil and extract powder of peony bark) And the matrix, and mixed, the matrix is selected from polyethylene glycol 6000 (weight average molecular weight), the viscosity of the polyethylene glycol is 14%, and the weight percentage of polyethylene glycol having a molecular weight of 6000 is 60%;

4. Heat the mixture to melt and stir evenly;

5. Add the above materials to the dropping machine, keep the temperature at 95 ~ 100 °C, and then drop in at the appropriate speed. In the methyl silicone oil of ~-8 ° C, after shrinking and forming, take out the methyl silicone oil and dry it.

比较例 Comparative example

2, the peony peel is distilled to extract the volatile oil, and the volatile oil of the peony bark is obtained, and the distillation is carried out for 8 hours. After the aqueous solution is collected, the hawthorn is added with 70% ethanol and refluxed twice, each time for 2 hours, the extract is combined, filtered, and the filtrate is ready for use; Rehmannia glutinosa, yam, and diarrhea are boiled with water. The first time, add 8 times the amount of water for 2 hours, the second time with 6 times the amount of water for 1 hour, combine the decoction, filter, and combine the filtrate with the above distilled aqueous solution, and concentrate under reduced pressure until the opposite. The clear paste with a density of 1.15 ~ 1.20, let cool, add ethanol to make the alcohol content up to 70%, stir well, let stand for 48 hours, take the supernatant and the above extract of hawthorn, decompression The ethanol is recovered to a non-alcoholic taste, and it is reserved; after boiling water, it is immersed twice at 80 °C, and each time 6 times of water is added, and the mixture is immersed for 1.5 hours, the leaching solution is combined, filtered, and the filtrate is concentrated under reduced pressure to the phase. The clear paste having a density of 1.15 to 1.20 (50 ° C) is combined with the above-mentioned stock solution, concentrated to a thick paste having a relative density of 1.30 (50 ° C), dried under reduced pressure, and pulverized into a fine powder to obtain an extract powder. Take the volatile oil of the peony bark and the extract powder for use;

3. Add the extract of Liuwei Dihuang according to the ratio of 1:1.55 (composed of volatile oil and extract powder of peony bark) And the matrix, and mixed, the matrix is selected from ordinary polyethylene glycol 6000 (weight average molecular weight), the viscosity of the polyethylene glycol is 13%, and the weight percentage of polyethylene glycol having a molecular weight of 6000 is 5%;

4. Heat the mixture to melt and stir evenly;

Table 1 Test data of Liuwei Dihuang Dropping Pills

项目 project	圆整率 Rounding rate	硬度 hardness	融散时限（分钟） Time limit for melting (minutes)
实施例1 Example 1	90 90	+++ +++	<15 <15
实施例2 Example 2	92 92	+++ +++	<5 <5
实施例3 Example 3	91 91	+++ +++	<10 <10
实施例4 Example 4	92 92	+++ +++	<5 <5
比较例 Comparative example	85 85	+++ +++	<28 <28

Note: The hardness is expressed in the attached table by placing the dropping pill on a glass plate and pressing it with a finger to observe the change in morphology. Among them, '+' means that the tap is deformed, '++' means forced deformation, and '+++' means that it is not deformed by force.

The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and combinations thereof may be made without departing from the spirit and scope of the invention. Simplifications should all be equivalent replacements and are included in the scope of the present invention.

Claims

Liuwei Dihuang Dropping Pill, which consists of Rehmannia, Hawthorn, Mudan Peel, Yam, Alisma and Poria. The extract of the traditional Chinese medicine is obtained as a raw material, and is prepared together with a carrier as a matrix of the dropping pills, and is characterized in that:

1) The weight ratio of the extract powder of the 6-flavored Chinese medicine to the substrate is 1 : 1 to 8 ;

2) The extract powder of the 6-flavored Chinese medicine is obtained by the method specified in the Pharmacopoeia or the ministerial standard;

3) The dropping pill matrix has a weight average molecular weight of 6000 and a viscosity distribution between 13.6 and 14.5. Polyethylene glycol, in the polyethylene glycol, the molecular weight of 6000 polyethylene glycol content of 40 ~ 60%;

4) Accurately weigh the extract and the substrate according to the above ratio, heat it in a heating container to melt, stir evenly, and then put it into the dropping machine at 75 °C ~ 100 °C, drip into the condensing agent of 30 ° C ~ -8 ° C, take out the dropping pills, wash and dry.
The Liuwei Dihuang dropping pill according to claim 1, wherein said 6 The extract of Chinese herbal medicine is powder, and is obtained by the following method: 1408 parts of Rehmannia glutinosa, 528 parts of peony skin, 704 parts of Chinese yam, 704 parts of hawthorn, Alisma 528. 528 parts and 茯苓 528 parts, the above six flavors, take 110 parts and smash into fine powder, and the remaining part of the sieve and the remaining simmered water are boiled three times, each time 30 Minutes, filtered, combined filtrate, concentrated to a thick paste; Hawthorn plus ethanol reflux extraction twice, each time 1 Hour, filtered, the dregs are reserved, the filtrate is recovered from ethanol, concentrated to a thick paste; the peony bar is steam distilled, and 1 mol/L is added to the collected distillate. The hydrochloric acid solution is crystallized, filtered, washed with water, dried at low temperature, and ground into fine powder; distilled aqueous solution and peony bark, hawthorn dregs and rehmannia root, yam and diarrhea are boiled three times, each time 1 Hour, filtered, combined filtrate, through the macroporous adsorption resin, with 70% Ethanol elution, collect the eluate, recover the ethanol, concentrate to a thick paste, add the above-mentioned glutinous cream, hawthorn thick paste and glutinous rice flour, mix, dry under reduced pressure, pulverize into fine powder, add the above-mentioned peony bark extract Powder, mix and get.
The Liuwei Dihuang dropping pill according to claim 1, wherein said 6 The extract of Chinese herbal medicine is powder, and is obtained by the following method: 1408 parts of Rehmannia glutinosa, 528 parts of peony skin, 704 parts of Chinese yam, 704 parts of hawthorn, Alisma 528. 528 parts and 茯苓 528 parts, the above six flavors, take 350 parts to pulverize into fine powder; Hawthorn plus ethanol reflux to extract twice, each time 1 Hour, filtered, the dregs are reserved, the filtrate is recovered from ethanol, concentrated to a thick paste; the peony bark is distilled by steam, and the distillate is added to 1 mol/L. The hydrochloric acid solution is crystallized and used; the distilled aqueous solution and the peony bark residue, the hawthorn dregs, the remaining barium, and the rehmannia root, the yam and the diarrhea are boiled three times, each time 1 After the hour, filter, combine the filtrate, concentrate to a thick paste; add the above-mentioned fine powder and hawthorn thick paste, mix, dry at low temperature, pulverize into fine powder, add the above-mentioned peony bark extract, and mix and obtain.
The Liuwei Dihuang dropping pill according to claim 1, wherein said 6 The extract of Chinese herbal medicine consists of extract powder and volatile oil of peony bark, and is obtained by the following method: 1408 parts of Rehmannia glutinosa and 528 parts of peony bark, yam 704 704 parts of Hawthorn, 528 parts of Alisma and 528 parts of medlar, the above six flavors, the peony bark is distilled to extract volatile oil, and the volatile oil of peony bark is obtained. The aqueous solution is collected after 8 hours of distillation; The ethanol is refluxed and extracted twice, each time for 2 hours, and the extracts are combined, filtered, and the filtrate is reserved; Rehmannia glutinosa, yam, Alisma Add boiling water twice, the first time adding 8 times the amount of water to cook 2, the second time adding 6 times the amount of water to cook 1 small, when the combined decoction, filtered, the filtrate and the above distilled aqueous solution combined, minus Pressure concentrated to a relative density of 1.15 to 1.20 The clearing paste, let cool, add ethanol to make the alcohol content up to 70%, stir well, let stand for 48 hours, take the supernatant and the above hawthorn extract combined, reduce the ethanol to a non-alcoholic taste, reserve; add water to boil After 80 °C Warm immersion twice, add 6 times of water each time, immerse for 1.5 hours, combine the leaching solution, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.15 ～1.20, and combine with the above-mentioned stock solution to reduce the relative density. A thick paste of 1.30, dried under reduced pressure, and pulverized into a fine powder to obtain an extract powder.
The Liuwei Dihuang Dropping Pill according to Claim 1, wherein the substrate is selected from a polyethylene glycol having a viscosity of 14 .
The Liuwei Dihuang Dropping Pill according to claim 5, wherein the weight ratio of the extract powder of the 6-flavored Chinese medicine to the substrate is 1: 1.55.
According to claim 1 The Liuwei Dihuang Dropping Pill described in the above, characterized in that the condensing agent is at least one of methyl silicone oil, liquid paraffin or vegetable oil.