DE2324534A1 - MIXTURE BASED ON POLYVINYLLACTAM - Google Patents

Description

The present invention relates to new mixtures, improved ones Preparations with a non-toxic carrier and in particular to improved pharmaceutical preparations for the delivery of pharmacologically active materials over a regulated, longer period of time as well as on processes for the production of such preparations and the stable aqueous products derived from them Emulsions.

It has been found that a pharmaceutical, neutral dosage form in in such a way that it is possible to use the contained therein to release pharmacologically active material on contact with the skin or the active material contained therein from the embedded medium or the Emulsion to be released over a long period of time after swallowing, causing one prolongs the pharmacological effectiveness and at the same time one gertaue Allows control of the amount of pharmacologically active material in the system,

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so that the desired effect is achieved. Ignition currently for these purposes The inert components used include high-molecular waxes that alone or in various combinations either evenly distributed around the active ingredients or melted first and then carefully over the small particles of the active components are applied (see, for example, the U.S. Patent 2,918,41i).

A disadvantage of using a wax for tablet formulations with long impact {i.e. Depot formulations) consists in that a relative large mass of wax must be incorporated into the dosage form to obtain the desired, to achieve long-lasting effects. In other words, that means the proportion of wax is several times greater in relation to the active component, which requires the production of a bulky tablet that can be swallowed makes it relatively difficult and uncomfortable for the patient.

Therefore, it can be seen that there is a current problem on the The field of pharmaceutical development is to produce a depot dosage form containing inert components with large surface areas that are non-absorbable, or if they are absorbable, any . Toxicity and undesirable side effects are practically absent »

The use of alkaline earth metal salts of saturated fatty acids in the Tablet production is known. These substances have been around for many years has been used as a tablet lubricant and filler; they are in the final tablet granulate immediately before compression in relative incorporated in small amounts to facilitate the compression of the grains without sticking to the punches and nozzles of the tableting machine.

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Furthermore, as is known, saturated fatty acids, their esters, ethers and Alcohols are tabletted with polyvinylpyrrolidone by converting the polymer in the presence of the saturated fatty acid or its derivative into a converts molten mass, granulates the gelled mass, reheats, cools, adds the therapeutic component and then at a temperature tabletted near the solidification point.

According to the invention it has now surprisingly been found that foods, those during the processing of a heat treatment with an accompanying decrease in nutritional value due to a partial or complete loss VAJrden subjected to carbohydrates, essential amino acids and vitamins, can process without losses. In order to compensate for the losses mentioned, the food is known to be consumed before processing has ended many nourishing components added. So are most canned foods, condensed milk products, dried protein products, grain products etc., enriched with amino acids, vitamins etc. However, some of these means of enrichment are even after prolonged treatments (sterilization), Attacked by light, moisture, oxygen or the temperature of the environment.

One of the many disadvantages of using saturated fat or Their derivatives in combination with polyvinylpyrrolidone for the production of depot formulations is their physical similarity to high molecular weight Grow * Due to their physical nature, large amounts of the saturated fatty acid substance used to achieve the desired effect will. So must the ratio of polyvinylpyrrolidone to saturated fatty acid material be about 1.7 or less. Furthermore are saturated fatty acids themselves are known to be inadequate as long-acting vehicles, even when combined with polyvinylpyrrolidone. This is how it is for excitement the desired prolonged effect still necessary a lot high

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molecular waxes, candelilla wax, beeswax, etc. in the formulation to incorporate. This further increases the bulkiness of the dosage form, adds unnecessary bulk to the bulk, and makes it easier to ingest much more difficult.

However, although it is possible to do so by using saturated fatty acid esalts to reduce the ratio of salt to polyvinylpyrrolidone, one encounters the difficulty that a complex formation between the salt and the polyvinylpyrrolidone is absent; This inherent disadvantage is immediately apparent when attempting to prepare an emulsion containing the active ingredients Contains polyvinylpyrrolidone and a water-insoluble hydrophobic chain end.

The aim of the present invention is therefore to circumvent one or more the disadvantages of the known technique.

Another object of the present invention is to manufacture a Polyvinylpyrrolidone powder melts are a derived, stable one aqueous emulsion.

-S-

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Another object of the present invention is to provide an enclosure of the active components in the complex, the active components having a prolonged Have a lifespan while creating a safe, ingestible, or applicable supplement.

According to the invention, a mixture should also be created that
active exposure time to various, externally applied preparations
prolonged and thus gives their sustained release.

The present invention relates generally to a mixture of about (a) 40-80 parts by weight of a polymeric N-vinyl lactam or a copolymer of this N-vinyl lactam with up to about 70% vinyl acetate, based on the weight of the copolymer, ( b) 20-60 parts by weight of a plasticizing agent, (c) 0.05-50 parts by weight of a medically active ingredient and (d) 0-99 parts by weight of solvent for components (a), ( b)
and (c); the present invention also relates to the stable, aqueous emulsions derived therefrom. The vinyl acetate is at his
Use in the copolymer preferably in amounts of 10-50 / a, based on the weight of the copolymer, incorporated, generally amounts of. 0.1-70% are possible.

The mixture can be made by adding the plasticizer
Tntntzt, the components (a) and (c) are added to form a melt,
and then let the mass cool down. After that, the emulsion can be made from this like that
formed mixture can be produced.

. X-

The mixture can be used in emulsion or melt mix form,
ie:

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Melt blend

pharmaceutical pills suppositories sucking preparation hair treatment preparation Cosmetic stick

absorbable surgical sutures

emulsion

Milk of magnesia

opaque soap, opaque cosmetic Silicone cream

white TiCL · Insect spray shoe care product

Anti-fogging agent for windshields

Car polish
Liniment

cosmetic day cream cosmetic lotion

Paper glue

{"donut") ·

Glazing for Berlin pancakes / chocolate sweets cake icing

Skin disinfectant hand lotion

Hair lacquer

liquid face powder

Suitable plasticizers include, for example, fatty acids, unsaturated fatty alcohols, Ethers of unsaturated alcohols, partially acetylated glycerides, etc., such as linoleic acid, oleic acid, linolenic acid, "Myvacet 7-00" (partially acety— lated monoglyceride from Distilled Product Industries).

The water-soluble N ~ vinyllactam monomer used according to the invention and the Polymers derived therefrom have the formulas:

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I. ^ R

R ₁ -CH C = O

GH = GH,

II. (Homopolymerized)

R ₁ -CH C = ^X N

CH-O-L-

-n

DabBi means R one to complete a 5-s, 6- or 7-membered heterocyclic ring system necessary alkylene bridging group; R. stands for

• κ
Hydrogen or an alkyl group / and η stands for a number indicating the degree of polymerization and usually has a value of at least 3 or 4 in the case of homopolymerization.

All of the polymeric materials represented by the general formulas above are commercially available and are referred to as polymeric N-vinyl lactams. They are obtained by polymerizing organic, 5-, 6- or 7-membered ones Ring compounds which contain the -NH-CO- group in their rings, e.g. 1-vinyl-2-pyrrolidone, 1-vinyl-5-methyl-2-pyrrolidone, i-vinyl-2-piperidone, N-vinyl- £ -caprolactam etc. Depending on the degree of polymerization they have a molecular weight between at least 300 up to a 000,000 or more. Usually viscosity measurements are used as an indication of the average Molecular weight of polymeric preparations applied; the polymers according to the invention are characterized by a chain of carbon atoms, to which the lactam rings are bound through their nitrogen atoms:

CH -

- CH - CH ₂ - CH - CH ₂ -

The (Fikentscher) K value of any particular mixture of polymers is calculated from the viscosity data and is suitable as an indication of the average Molecular weight of this mixture. Its purpose is in

"Modem Plastics", 23, No. 3,157-61, 212, 214, 216, 218 (1945) in more detail / * preferably one with 1-4 carbon atoms

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and is defined as 1DD0 times k in the empirical relative viscosity equation:

L 75k ³ + k

C 1 + 1.5 kc

G means the concentration in g per 100 ecm polymer solution, and h -. is the ratio of the viscosity of the solution to that of the pure solvent. To avoid decimals, the K values are given as 1000 times the calculated viscosity coefficient. According to the invention, polymeric N-vinyl lactams with a K value of about 10-100, preferably 15-90, can be used. If emulsions with a higher viscosity are desired without increasing the solids content of the melt, then polymers with a higher molecular weight, for example _:. to produce the melt mixture.

The K values and specific viscosities (*]) can be converted into one another and related by the relative viscosity (^,). The viscosity measurements are therefore carried out on solutions with a concentration of 1.00 g polymer per dl solution at 25 C. (c = 1), then the relationships are as follows:

'rel "sp relative viscosity ^ = specific viscosity plus 1

relative viscosity = 10 / "0.001K-jU, 00D075K ² / (H €, 015Kji7 Thus:

η = - -10 / 0, D01K-rö, D00D75K ² / (i-fD, D015K] 7 ~. ¹

The relative viscosity, specific viscosity and K are dimensionless, while the inherent viscosity

HU

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and the intrinsic viscosity number (the limit of inherent viscosity, when C approaches 0) the dimensions of the dilution, i.e. the reciprocal Worth the concentration, have. · ·

The number of recurring polymer units indicated by "n" in the square brackets of the above general formulas or the extent of the polymerization corresponds to a chain of approximately 4-20,000 monomer units or more. In practice, a mixture of polymeric molecules is always used

one
produced, each containing / different number (n) of monomer units. The polymers are readily prepared by the process steps of US Patents 2,265,450, 2,317,804, and 2,335,454, in which working examples are given for each of the species represented by the above formula. The patent specifications mentioned are hereby included in the present application.

The ratio of N-vinyl lactam to plasticizer can be varied depending on what type of melt blend or emulsion is desired. For example, form melts with more than 50 ⁰ Yes Plastizierungsmittel soft and pliable films and are therefore suitable for ^coating foods or tablets. The melts formed with high molecular weight, polymeric N-vinyl lactams to produce stronger and harder films are easier to pulverize. The thickness of the emulsion is a function of the amount of melt to the solvent and not of the amount of polymer in the melt. In the same way, the emulsion viscosity can be kept very low to allow it to pass through the nozzle of an aerosol spray can.

The Melt The present invention is directed generally to the mixing / of once

(PVP]

Polyvinyl lactam (PVL.), Such as poly-N-vinylpyrrolidone / ^ or a copolymer from an N-vinyl lactam and vinyl acetate in hot water under vigorous

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- 1C -

Agitation, creating a melt / water emulsion. The quality of the Emulsion depends on the water temperature, the stirring and the type of melt away. Water / melt emulsions can be made by either the hot melt is added directly to the hot water, or by indirectly adding the powdered melt material to the hot water. The melts can also be emulsified in lukewarm or cold water; however, this method requires more time and mechanical agitation. aside from that the latter emulsions are not as stable as those at 90-100 C. produced emulsions (they tend to separate more quickly).

The components mixed in the hot melts or enclosed in the cold melt matrix are preferably emulsified together with the melt. The physical properties of such emulsions depend on the melt to water ratio and on the type and amount of unsaturated fat material used in the original melt. Emulsions with an emulsified melt content of 40 % or more can be regarded as lotions or creams of high viscosity. Emulsions with less than 40 % solids per year are considered liquid lotions or aqueous emulsions of low viscosity. ,

The emulsion stability and spreadability properties depend decisively on the type of melt to be emulsified. A "melt" composed of a poly- N-vinyl lactam and partially acetylated glycerides or fatty acids forms better emulsions than one composed of the corresponding alcohols or ethoxylated alcohols. Branched chain fatty acids make better ones

-v. emulsions as the linear analogues of the same fatty acids; Unsaturated fatty acids also form better emulsions than saturated acids. Emulsion stability, spreadability, etc. also depend on the ratio of poly-N-vinyl lactam to unsaturated fat component in the melt. The best

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Emulsions are obtained when the concentration of the unsaturated fat component is equal to or lower than the concentration of poly-N-vinyl lactam or copolymer. Melts with a high concentration of the "fat" component do not form stable emulsions. Thus, we achieved stable emulsions when the composition of the melt preferably 40-80 ⁰ Yes poly-N-vinyl lactam or copolymer of vinyl lactam and vinyl acetate and 60-20% unsaturated fatty component comprises.

As with poly-N-vinyl lactam or mixed polymer melts, melt emulsions are sions intended primarily for pharmaceutical and veterinary purposes. However, they can be used in (i) the food industry, especially in the treatment of cereal and baked (flour) foods; 2. Can cosmetic emulsions (direct or modified) as moisturizing and skin conditioning preparations in the form of Lotions or creams are used; the emulsions are also good, opaque making compounds for various cosmetic preparations, such as cream rinses, cream conditioners, etc.

Other uses include:

1.) Various pharmaceutical components, such as vitamins, aspirin, MgO etc. ,,

can be included in safe and stable emulsions.

2.) The components enclosed in melt emulsions can be unpleasant Mask the smell or taste.

3.) Vitamins and other nutrients can be embedded in melts.

4.) The emulsions produced in this way can then be applied to grain · and other foods are sprayed on.

5.) The melt emulsions should be suitable for use in edible mixes Comply with US Food & Drug Administration regulations.

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6.) The melt emulsions can be applied as a cream or lotion per se or formulated with other components.

7.} The emulsions can be used as a safe means of opacifying in Food, drink or cosmetics.

You can add 70 parts of poly-N-vinyllactam or copolymer to about 30 parts Plasticizing agent, but preferably about a 55:45 ratio use. In the emulsion, the ratio of PVL / plasticizer / Water 1: 1: 98 to 40:40:20.

The novel mixture according to the invention comprises, as main components of the formulation, one or more therapeutic agents distributed in a molecularly dispersed poly-N-vinyl-latam or mixed polymer phase; a network is formed around the macrophase of the water-insoluble, hydrophobic, unsaturated fatty acid or fatty acid component, with. Use — the poly-N-vinyl lactam fatty acid constituents are present in the form of the melt in a ratio of about 0.5: 1 to 4: 1 of poly-N-vinyl lactam to plasticizing agent. The active component is dissolved or dispersed in the molten mass of poly-N-vinyl lactam and plasticizer immediately before the mass is removed from heating. After cooling, the molten mass forms a solid film that can later be granulated into a powder or directly emulsified. It is found that the ratio of poly-N-vinyllactam or copolymer to the unsaturated acid component is not critical and can be varied over a considerable range, which depends on the desired rate of release of the active component. Is the above ratio of. about 0.5: 1-1: 1 _f then the active ingredient is released in about a few hours. At a ratio of about 3/4 to about 1.5: 1-2: 1, the active ingredient is released over a prolonged period of more than 5 hours. Is this

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3: 1-4: 1
the ratio of about 1: 1 to about / then release occurs over a substantially longer period of about 12-24 hours. All of the times given above can of course be influenced by a large number of variables, such as constituents, changes in components, and so on.

Although the mechanism for the gradual release of the active ingredient over-extended time from the new combination according to the invention not yet has been determined absolutely, it is almost certainly believed that the desired effect is due to the particular physical combination of the Components, compatibility, solubility parameters and joint action during absorption on the surface to which it was applied, is achieved.

In the production of the emulsion, according to the invention, the melt is turned away to a sufficient volume of water added to the dry melt containing the prescribed amount of unsaturated fatty acid component, poly-N—

same

vinyl lactam or copolymer / and active ingredient and optionally contains any other constituents to wet (more dispersed or emulsified), the active constituent dissolved in the added water becomes, if it is water-soluble, at the same time in the aqueous poly-N-vinyllactam- or mixed polymer phase distributed. If, on the other hand, the active ingredient is insoluble in water, then it becomes with the unsaturated fatty acid component in dispersed in the non-aqueous phase. The active component system, Poly-N-vinyl lactam, or mixed polymer and water, flows easily around the hydrophobic fatty acid microparticles. On the other hand, the microparticles composed of an active ingredient and a hydrophobic, unsaturated fatty acid component evenly in the aqueous poly-N-vinyl lactam or mixed polymer system dispersed.

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■ - 14 -

If the preparations described above come into contact with digestive juices " come, then the aqueous medium infiltrates the mass of hydrophobic fatty acid component at a slow, constant speed by connecting the network— works because of the hydrophilic polymer film by capillary action. The molecules of the active ingredient are found in the digestive juices Point of contact of the latter with the polymeric film containing the drug solved. The dissolved active ingredient is then free into the surrounding area Diffuse area and the body and is available for absorption. Because of this mode of diffusion of the drug from the emulsion, there is no Break the fatty gum mass, and the mixture acts as an inert carrier for the active ingredient.

It should be borne in mind that - whether by solid or by emulsion - essentially two competing forces in this mix work while they are runs through the digestive tract and is embedded in the aqueous flowable material, namely the hydrophobic barrier of the unsaturated fatty acid component and the surrounding hydrophilic film of polymer and active component. This makes it easy to control the dissolution of water-soluble therapeutics, by measuring the amount of hydrophobic material in the preparation or mixture increased or decreased. That is, by adding a relatively high proportion of the fatty acid component compared to the polymer, the active constituents are released over a long period of time. By reducing this ratio, on the other hand, makes the therapeutic component shorter Time set free. So one uses the unique, hydrophilic, non-swelling film-forming Properties of the poly-N-vinyl lactam or its copolymer compared to the effect of other commonly used components that do not have these physical properties. Where the

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active ingredient is not soluble in water, provides the unique ability of the polymer to form a complex with the fatty acid component and thus to form an emulsion the preparation has the option of being in an emulsified phase in which the active ingredient is in the non-aqueous Phase is to remain practically uniformly dispersed.

Therefore, it is easy to see that the novel preparation of the present invention for many different purposes in the pharmaceutical field as it is a method of administering water-soluble and water-insoluble therapeutics alone or in admixture with other substances allows a controlled period of time with predictable regularity and delay. The drugs suitable for use in the new preparation include antihistamimes, central nervous system depressants, Central nervous system stimulants, vitamins, antibiotics, gastric acid agents, cough suppressants, etc. These can be either in In the form of water-insoluble bases or as their water-soluble salts, whichever is the most advantageous, can be incorporated into the new preparation absorption mode found. ·>

Although the unsaturated fatty acid is a crucial component in the invention Preparation is used, it is incorporated in the melt blending process. That is, it is melted first, and then that became polymeric material is added along with the other ingredients, making it an integral part of the preparation.

Regarding the incorporation of other commonly used extenders there is none in the formulation of the new combination according to the invention Restrictions. So can indicated as a diluent in any Amounts of components such as calcium dibasic asphate, lactose, mannitol, etc. can be used. Bums, such as acacia or

309849 / Π 887

- 16 tragacanth gum, are used. "·

The following examples illustrate the present invention without limiting it. Unless otherwise specified, all parts and ratios are parts by weight and ratios by weight.
General process for producing the melts The plasticizing agent (fatty alcohol, unsaturated fatty acid, partially acetylated glyceride or ethoxylated fatty alcohols or mixtures of these components) is heated to 133-150 ° C., then a polymeric N-vinyl lactam, e.g. a PVP, is slowly added with stirring -with a K-value of 29-32, K-30 or 90, or a. Vinyl pyrrolidone / vinyl acetate copolymer added. After all of the polymeric lactam has been added, stirring is continued for a few minutes, then the component to be embedded is added to the molten mass, stirring is continued for a few minutes, then transferred to a bowl or container and allowed to cool. Then the solid matrix is broken into smaller pieces and pulverized in a mill. The composition of the melt can be summarized as follows: Ti

PVP or mixed polymer made of VP / VA * 40-80

Plasticizing component 20-60

active component 0.05-50

It is difficult to use more than 70 parts of PVP alone or as a VP / VA blend in 30 Share plasticizer to dissolve. Hence the ideal ratio is 55 parts PVP / 45 parts plasticizer.

The copolymer of vinylpyrrolidone and vinyl acetate can be prepared according to known Process are produced. .

* or in general: PVL or mixed polymer from VL / VA

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Manufacture of melt emulsions

1. Procedure with the addition of hot melt to hot water Distilled water was brought to the boil, then 80 g of the same in weighed in a beaker and transferred it to the container of a Waring «mixer, which is heated by a heat source directed towards the base of the container. became. 20 g of hot melt (100 g or more) were added with vigorous stirring transferred to the Waring mixer, then stirring was continued for 10 minutes. That Mixing was stopped and the emulsion transferred to another container.

2. Powdered melt to hot water

The process of making emulsions from powdered solids is similar to the procedure described under 1.). Instead of adding hot melt, the pulverized material is slowly added with vigorous mixing at constant heat. After the addition of the whole pulverized material was further stirred for 10 minutes and that emulsified

Material then transferred to a container.

Comparative examples Investigation of the melting properties of PVP stearyl alcohol Example A.

7. g of polyvinylpyrrolidone ( ³ VP) were dissolved in 63 g of molten stearyl alcohol until gelling, the gelled mass was cooled to room temperature, crushed and passed through a No. 10 mesh sieve and No. 16 mesh sieve '.

Example B.

Example A was repeated with twice the amount of PVP, with the Amount of stearyl alcohol remained the same. Thus the PVP was: stearyl alcohol

Ratio 1: 4.5.

The PVP easily dissolved at 70 ° C. Half of this melt was up left to cool; the other half was further heated to 145 ° C, and

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then left to cool. At both temperatures, the enamel appeared to be homogeneous to be. ·

Example C

A PVP: stearyl alcohol ratio of 1: 2 ^ 25 was used; the PVP did not melt easily and completely at 70.degree. At 70 ° C. the enamel matrix was a slurry of unmelted granular PVP in stearyl alcohol. The PVP melt was homogeneous at 140 ° C. in the molten and solid state. Example Cl »

JE, a PVP: Stearylalkohal ratio of 1: 1. At 70 ° C. only part of the PVP material in the slurry appeared to be compatible. The cooled enamel matrix contained a large proportion of granular PVP.

At 140 C. all of the PVP melted and formed a homogeneous, transparent one Mass that, after cooling, formed a smooth, translucent matrix.

The compatibility of PVP stearyl alcohol melts with a candelilla wax in a ratio of melt to wax of 7: 8 at 80 C. is in the listed in the following table.

Table 1

ratio of

Temperature of manufacture Compatibility of PVP melt PVP: stearyl alcohol d. PVP melt; ° C. and candelilla wax

1: 9
1: 9

1: 4.5
1: 4.5 '

1: 2.5 1: 2.5

1: 1 1: 1

compatible

incompatible

Il

Il Il

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- 19 The production of PVP stearyl alcohol emulsions from PVP melts is in

Table 2 described.

Table 2

Ratio of production temp. PVP / stearyl alcohol d.PVP melt; C.

Appearance of the emulsion

1: 9

1: 4.5
1: 2.5

1: 1

70

140

70

140

70

140

70 '140

Example 1_

partially acetylated monoglyceride ("Myvacet 7-00")

PVP ¹¹ K 29-32 ".
Vitamin ^M C "(Merck)

did not form an emulsion; two separate layers as above as above as above

some erauled product, most of the stearyl alcohol however failed

as above

as above

completely homogeneous and smooth emulsion

45 g

55 g
10 g

Master position of the melt

A beaker containing the plasticizer ("Myvacet") was placed in a Given an oil bath, the plasticizer to 145-153 ° C. heated and the PVP sieved in within 10 minutes with constant stirring. After about 2 After standing for minutes, the vitamin was added within 1-2 minutes. The mixture was immediately cast into a film on a Mylar sheet and let cool down. Then the film thus formed was crushed and some Put pieces together with a small amount of dry ice in a beaker, after which a few minutes or until the material is granular or powdery was, was married. After transferring to a Petri dish, the Drying and preventing moisture build-up placed in a dessicator.

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Production of the melt emulsion Z O 2 4 5 3 A

A mixer container was placed on the mixer stand, and a heater The source was directed at the lower end of the container. A 10 g portion of the powdered melt was weighed out and set aside. A Calves containing distilled water were heated to a boil, then 40 g of boiling water were immediately transferred to the mixer tank. Portions of the .pulverized melt were added intermittently, after

each addition was mixed until all of the melt had been added. After finished Mixing was continued for about 10 minutes.

The temperature of the emulsion after mixing was about 80 C. Example 2

Example 1 was repeated for the preparation of melt and emulsion, wherein the melt was composed of the following components:

Stearic acid (for food use) 45 g PVP ("K 29-32") 55 g

Riboflavin (Merck) 1 g

• Example 3__ ■ '

Example 1 was repeated, with the melt production using the Acetylsalicylic acid and the phenacetin were added within 5 minutes became.

Stearic acid (for food purposes) 22.5 g

PVP ("K 20-32") 27.5 g

Acetylsalicylic acid x 12.5 g

Phenacetin 7.5 g

Example 4_

Example 1 was repeated, except that the zinc oxide was used in the production of the melt was added within 4 minutes.

Stearic acid (for food use) 45 g PVP ("K 29-32") 55 g

Zinc oxide 10 g

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Example 1 was repeated with the following ingredients for the melt: ''

partially acetylated monoglyceride

("Myvacet") 45 g

PVP ("K 29-32") 55 g

Thiamine (Merck) 10 g

Example 6

Example 1 was repeated with the following ingredients for the melt:

partially acetylated mono glyceride

("Myvacet") 45 g

PVP ("K 29-32") 55 g

Magnesium oxide ("heavy USP") -jo _g

Example 7

Example 6 was repeated, with 10 g of game as part of the emulsion. Cherry syrup were added.

Example 1 8

Example 1 was repeated with the following components of the melt, where the following was pulverized in a Wiley mill:

Stearic acid 45 g

PVP ("K 29-32") 55 g

Cyancobalamin (Vitamin B.pj Merck) 1 g

Example 9

Example 1 was repeated, pulverizing in a Wiley mill:

Stearic acid 45 g

PVP ("K 29-32") 55 g

Aquapalm (vitamin A palmitate;

Hoffman-La Roche) " ⁹

Example 10

Example 1 was repeated, pulverizing in a Wiley mill:

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Stearic acid. 45 g 23245 3 A

PVP ("K 29-32") 55 g

Di- © (-tacophenyl acetate NF-FCC (Vitamin.

E acetate; Hoffman-La Rache) ⁹ "

Example 11_

Example 1 was repeated with the following components of the melt:

partially acetylated monoglyceride _cr .
(«Myvacet») ^{60 g}

PW ("K-9Q") 40 g

Example 1j2_

Example 1 was repeated with the following components of the melt:

Stearic acid 70 g

PW ("K-90") 30 g

' Example 13

Example 1 was repeated with the following ingredients ι partially ace-tyliertes monoglyceride _FLR
(Myvacet ") ^{4b p}

Mixed polymer of vinylpyrrolidone / _ "

Vinyl acetate fPVP / VA) (with a VA content ^{5b v} 9 of 70, 50 or 3U Gevv. 7o-]

Example 14_.

Example 1 was repeated with the following ingredients:

1-octadecanol '50 g

PW ("K-30"). . - "'' 5Qg

Example 15 .

Example 1 was repeated with the following ingredients:

Isostearic acid 45 g

.PVP ("K 29-32") 55 g

Example 16

The procedure was as in Example 1-10 , where instead of "Myvacet"

Oleic acid was used.

The emulsion was prepared as follows:

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232A53A

- 23 - "

Distilled water was heated to boiling, 400 g of the same were weighed and transferred to a pre-heated mixer tank. The hot melt was added directly to the water, it was mixed for 10 minutes, and then the emulsion was transferred to a clean container.

Oleic acid. 45 g

PVP ("K 29-32") x 55 g

Example 17

The melt was prepared using isostearic acid instead of "Myvacet 7-00" as in Example 1. The emulsion was prepared as in Example 16, but using 150 g of water; while the 40% emulsion was thicker and creamier than 2O ^c / o emulsion of Example

Isoearic acid. 45 g

PVP C ¹¹ K 29-32 ") 55 g

Example 18

The melt was made using oleic acid instead of "Myvacet" like produced in example 1. The emulsion was prepared as in Example 16, but using 66 g of water; was there Emulsion very thick, creamy and smooth.

Oleic acid 45 g

PVP ("K 29-32") 55 g

Example 19

Method of making a cream conditioner opaque

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Formulation by weight - ° / o --_________

80:20 quaternized polyvinylpyrro-

lidon-dimethylaminoethyl _{methacrylate- Q 5Q} ( _{as 1DQ} Oj ₀ solids) copolymer in alcohol solvent '

ethoxylated lanolin alcohol (100 mol _{Q 15} ethylene oxide; "Ethoxylan 100"; Malmstrom) '

"Ethanol SDA-40" "- 15.00

"Methyl paraben USP" 0.10

least. Water 82.25

Emulsion of Example 18 (60 p / oig) 2.00

100.00 The emulsion obtained gave a cream rinse a milky appearance.

Example 20

"_Method of making a conditioner opaque:

formulation _; Weight ~%

8Q: 20-quaternized polyvinylpyrrolidone

Dimethylaminoethyl methacrylate mixed poly (100% solids) merisate in water as a solvent. '

Ethoxylate isostearyl alcohol (10 mol E.0; η nn "Emulphor AM-650") u, uö

Dimethylpolysiloxane / polyethylene oxide /. Polypropylene oxide copolymer 0.08 ("Silicone SF-1066-G.E.)

. Perfume IFF No. 3159-E D, 10

"SDA-40" 32.90

Disodium salt of 4-X "/ 4- (N-ethyl-p-sulfobenzylaminoj-phenyl / - (2 ^ -sulfonium phenyl) - methylene1 / _1-Ν- ethyl-N - ^> - sulfobenzyl- A ² » ⁵ -cyclohexadienimine ("FDC" Blue ^D ' ^1D No. 1, 0.6% H. Kohnstamm & Co.) -

Stearyldimethylbenzylammonium chloride η in ("Ammonyx 490; Oxyx Chemical Co.) U, IU

least. Water ^v 62.09

60-day emulsion from Example 18 2, DO

1DD.0D The addition of the emulsion prepared in Example 18 made the clear condi-

tioning setting lotion opaque.

309849/0887

Formulation of a moisturizer for dry skin

Parts by weight of formulation g

60% emulsion of Example 18 100

Multistearol non-ionic smoothing agent ("Amerchol L-101-A") (Sterol and 25 higher alcohols are only available in their free form)

Isopropyl ester of a highly purified lanolin fat acid ("Amerlate P")

Dimethylpolysiloxane / polyethylene oxide-polypropylene oxide copolymer 1

("Silicone SF-1066-G.E.")

Perfume q.s.

Preservatives q.s.

In preparing the above cream / 100 g of the emulsion of Example 18, "Amerchol L-101", "Amerlate P" and "Silicon BF-1066" were added with slow mixing, followed by the addition of perfume and preservative. Example 22

Example 16 was made using linoleic acid in place of oleic acid repeated. . .

Example 23

Example 16 was made using linolenic acid in place of oleic acid repeated.

The terms “unsaturated fatty acid component”, “unsaturated fat component” and “fatty acid component” used in the present application generally encompass any plasticizing agent which can be used according to the invention. .

Evidence of complex formation by IR spectrophotometry In order to determine complex formation between PVP ( ¹¹ K 30 "), fatty acids, fatty alcohols, partially acetylated monoglycerides, etc., an IR investigation was carried out using alcohol and chloroform solutions and

309849/0887

physical mixtures of PVP and fatty compounds to make any Determine frequency shifts. . ·

All samples of Table 3, with the exception of Sample T, are 30- ^ solutions in undenatured alcohol or chloroform a mixture of each the various fatty acids - alcohols - partially acetylated

Monoglyceride / 'and 55% PVP ("K-30"). The solutions were prepared by PVP and the other components were added separately to the solvent.

Sample 1 is a reference standard and consists of a solution of only PVP ( ¹ K-SQ ") in undenatured alcohol.

For each sample from Table 3, the IR spectrum in liquid (solution) and solid (film) state. The film was obtained by evaporation the solution on a CsBr window at 100 C. for 5 minutes in one Vacuum furnace.

Reference Sample 1 made of PVP ("K-30") showed no shift in frequency (actual position of the absorption band cm) when recorded as solution or film, while all other samples when recorded as film showed a change in frequency "

The samples of Table 4 were made by the KBr process; i.e. the sample was finely ground and mixed with powdered KBr, whereupon compressed under pressure to form a clear tablet.

A reference sample made of PVP ( ^w k-30 ") - ⁽ alone absorbs at 1550 cm" j also PVP ("k-aO") itself absorbs at 1650 cm " ¹ '.

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A physical mixture of 45% stearyl alcohol prepared in a Waring blender, and 55 $ PVP "K-30" also absorbs at 1650 cm, while a similar, prepared by melting the two components

-1 mixture absorbed at a higher frequency, namely 1660 cm.

A melt mixture of different concentrations of "Myvacet 7-00" and PVP "K-90" shows an increase in frequency when the PVP concentration is increased.

With a quantity of PVP "K-90" of 100 ^ο / ά there is no frequency shift.

309849/0887

Table 3 IR spectroscopy data of PVP / plasticizer mixtures

Sample formulation

1. PVP-. "K-30" (100 '«/ α)

2. 'Stearic acid + PVP ("K-30")

Isostearic acid + PVP. ("K-30") Oleic Acid + PVP ("K-30") Linoleic acid + PVP ("K-30") myristic acid + PVP ("K-30")

3. Stearyl alcohol + PVP ("K-30") Isostearyl alcohol · + PVP ("K-30") Cetyl alcohol + PVP ("K-30"), oleyl alcohol + PVP ("K-30")

•. Isostearylalk. + 1 EO + PVP "K-30""Isostearylalk. +3 EO + PVP" K-30 "'Isostearylalk. + 5 EO + PVP" K-30 ¹ !'

4. "Ms <vacet 7-00" + PVP ("K-30")

5. Stearic acid + PVP ("K-30") linoleic acid + PVP ("K-30") isostearylalk. + 3 · E.O. + PVP

• Blyvacet 7-OD

* β undenatured alcohol ** * = -CON band of PVP "K-30" position of the absorption bands **; medium 'solution film

Ethanol *

Il If Il Il Il

Il Il Il Il It Il Il

1652

1650 1650 1650 1650 1650

1650 1650 1650 1650 1650 1650 1650

1650

1655 1652 '1652

none

1651

166S 1662 1668 1660 1661

1653 1660

1660

1660

1660 1665 1662

1662

1670 1663 1645 none

(Jl Ca)

Table 4

IR spectroscopy data of physical PVP plasticizer mixtures and melt mixtures using the KBr method

Sample Description '· ■ Position of the absorption band *

cm"

6. Melt blend of 45% stearylalk. + 55% PVP ("K-30"). , 1660

• 7. PVP Γ "K-30"). 165

PVP ("K 29-32") '. '1650

8. physical (Waring) mixture of 45 * / "Stearylalk. + 55% PVP ("K-30") 1645

9. physical (Waring) mixture of 45% stearylalk * + 55% PVP ("K-30") 1650

10. Melt mixture off.

90% "Myvacet 7-00" ** + 10% PVP ("K-90") 1640

JS * 80 # "■ ■ + 20%" '"1649

S 70% "+ 30 ° /.""1660I ₁ ,. ....

S 60% «+ 40 ^"" ₁₆₆₁ 1 complex formation

4N 0% "+ 100 '%"'. ' 1640 ι

"^ * m -CON Band of PVP" Κ-30 "or" K-90 ", comparable to the film values of Table 1 OO. **« Distilled acetylated monoglyceride, derived from hydrogenated beef tallow, in which about ⁰ ^ 2/3 of the free OH groups are acetylated} Distillation Products Industries, Division of Eastman * · * 'Kodak Comp.} Kodak / DPI Product Bulletins A-1 (6/15/72) and ZA-22 (1S69)

• ■ cn

From the data in Tables 3 and 4 it can be concluded that some Formation of complexes between mixtures of PVP and various compounds, how. Fatty alcohols, oxyethylated alcohols, fatty acids, some of which are acetylated Monoglycerides, etc., takes place. No complex formation occurs with physical Mixtures of PVP / fatty acid films made from solutions and Samples that were only mixed (see Tables 3 and 4).

Furthermore, it can be seen from Examples 1 to 6 that at one temperature over 100 C, d. H. at about 130 C, a complex is formed when the Fatty acid or the fatty derivative prior to the addition of the poly-N-vinylpyrrolidone is heated. Where not above 100 ° C. was heated, there was no complex formation between the fatty acid and the poly-N-vinylpyrrolidone. Furthermore, stable aqueous emulsions are made from most unsaturated acids, like linoleic acid, linolenic acid, oleic acid, formed while going from saturated Fatty acids and fatty acid derivatives received poorer emulsions.

309849/0887

Claims (1)

Claims 1. - Mixture, consisting of (a) a polymeric N-vinyl lactam in complex combination with (b) a member from the group of unsaturated fatty alcohols, unsaturated fatty acids, partially acetylated monoglycerides and ethoxylated unsaturated fatty alcohols. 2. ' Mixture according to claim 1, characterized in that it contains a monoglyceride of an unsaturated fatty acid. 3.- Mixture according to claim 1 and 2, characterized in that the unsaturated The residual fat in the compounds (b) is 12-3o, preferably 14-22, carbon atoms. 4. Mixture according to claims 1 to 3, characterized in that they are approximately (A) 40-80 parts by weight (i) of a homopolymer of an N-vinyl lactam from Formula: R - PH ¹ ^ CH = CH ₂ 'in which R stands for an alkylene bridge group with 2-4 carbon atoms necessary to complete a 5-, 6- or 7-membered heterocyclic ring system and R stands for hydrogen or a lower alkyl group, preferably with 1-4 carbon atoms, or (2) one Copolymer of the N-vinyl lactam with up to about 70 % vinyl acetate, based on the weight of the copolymer, (b) 60-20 parts by weight of a plasticizer including (c) 0.05-50 parts of a medically active ingredient and (d) 0-99 parts of solvent for components (a), (b) and (O) includes. 309849/0887 5.- Mixture according to claim 1 to 4, characterized in that the copolymer from about 50-90 parts of N-vinyl lactam and about 50-10 parts of vinyl acetate consists. . 6, - mixture according to claim 1 to 5, characterized in that the N-vinyl- lactam Ν — is vinyl pyrrolidone. 7.- Mixture according to claim 1 to 5, characterized in that component (a) is poly (N-vinylpyrrolidone). " 8, - Mixture according to claim 1 to 7, characterized in that the component (b) is linseed oil, linolenic or oleic acid. 9. Mixture according to claims 1 to 8, characterized in that component (d) is water. 10.- Mixture according to claim 1 to 9, characterized in that the component (c] is therapeutically active. 11.- Mixture according to claim 1 to 10, characterized in that the component (c) is soluble or insoluble in water. 12. Mixture according to claims 1 to 11 in the form of a stable aqueous emulsion. 13. Mixture according to claims T to 11 in the form of an aerosol containing a propellant. 14. Mixture according to claims 1 to 11 in the form of a plasticizer containing skin cream. 1.5 - mixture of claim 1 to 11, characterized in that it is in molten form at a temperature of about 100-150 ⁰ C.. 309849 / 08S7 16. A method for producing a mixture according to claims 1 to 41, characterized in that characterized in that components (a), (b) and (c) (according to the above Definition) heated to a molten mass and then allowed to cool. 17. Process for the preparation of a mixture according to claim 1 to 11, characterized characterized in that component (a) is added after component (b). heated. 18.— The method according to claim 17, characterized in »that the mixture also contains a component (c) as defined in claim 4. 19.- The method according to claim 1 to 18, characterized in that one is on a temperature between 10Ü-150 C. heated. The patent attorney: 309849/0 88 7