Anti:haemorrhoidal rectal insert

SUMMARY

Method for the treatment of hemorrhoids

x ................... -.....- ................. ...... - - · · · .........-......... y jChe consists of ¹ introducing into the rectum of a subject afflicted by these an insert having a substantially cylindrical shape, comprising a swollen polymer in water having a water content of at least 35% by weight, said insert being.

Previously frozen by subjecting it to a temperature below 0 ° C for a period of time sufficient to freeze the free water. Containing and maintaining said insert with at least one portion thereof outside the sphincter muscle; this.

BONGlOVANNt Guido

/ i

k 1 ago. · /

Hemorrhoids are swollen varicose veins

In the mucous membrane inside or immediate | mind outside the rectum. j

I A common cause of hemorrhoids is the *

justa and effort to eliminate hard stools ^

Jasciutte. The excessive pressure causes one of the membranes of the rectal membrane to slide

.....^f 1 below, pinching the veins and irritating them. ί '...........' ΐ i

J Women during pregnancy are part4!

larmentesoggette to the problem of hemorrhoids a!

because of the pressure in the veins in the inferior zone -; t ................... i jre of the body. J j!

Other causes are the malign of the dying tract resulting in an anal infection, it is cirrhosis of the liver, which obstructs the flow of blood and applies greater pressure on the hemorrhoidal veins.

; Once the hemorrhoids are formed, ί

jesse may further deteriorate or break due to additional pressure during constipation ι

Je strain on the stool, or by foreign pressure

I! na due to prolonged sitting position (detail

I mind if the hemorrhoids are prolapsed or external), j The broken and bleeding hemorrhoids are sensitive to infections; the swelling caused i

2.

λ KIWI fluid from Inflammation affects, in turn, on hemorrhoids by compressing the veins.

The problems of hemorrhoids are auto-gccele: and the prevention of the progressive detertainment of the problem is the essential condition for a treatment destined to success.

, Treatment methods vary from t baths:

warm to ointments and suppositories, and to surgery or chemotherapeutic injection to check the memory and to eliminate varicose veins. Often several methods are combined for indiriz.1 ... ..._c_:on the various aspects of the disease.

the

One approach to treatment is to relieve pain and decrease swelling (cooling the hemorrhoidal tissue.

t I <

] t ιCowie in U.S. Patent No. 969.134 proposes ί i!

• the use of a cable insert filled with frosted ice or another cooling medium_? the ι!

f which is reintegrated for each use.

ί ί More recently, Harris in the patent statu! nitense No. 3.939.842 proposes a rectal insert i

plastic with a freeze liquid, preferably water, encapsulated, provided with a collapsible bulb end. Both previous devices have several common drawbacks:

AR1KII / C

3.

1) the surface of the device may have a very low temperature so that it may cause freezing in the sensible rectal tissue. Freezing occurs when the intracellular fluid is frozen, breaking the cell membrane - - ................................. ...

jre. This can also occur at moderate temperatures ........

Below the zero if the contact between the device1 ...........

jive and the fabric is intimate and the transmission of i

heat is effective, as is the case for both.

the devices.

THE

2) None of the devices is intrinsically + .......'.............-..........

Disposable tea, which can increase the danger of infection. Although the Harris device is .........!

I is expected to be disposable, it lacks any characteristic that prevents its multiple uses. Its presumably higher cost;

I. t if compared to ointments or suppositories, it can encourage its multiple use.

; 3) Both devices have a single function, the cooling of the fabric in the channel * ......!

ι!

rectal ile. This treatment must be combined! with other means, such as ointments, lubricant, suppositories, etc., which integrate the treatment »r

I and the elimination of discomfort by administering some medications, protective layers and lubricants mentioned above ⁴r

BONGIOVANNI Guido t "

the swollen tissue and by possible rammoll (stool).

4) None of the devices can be applied without a lubricant.

Thus, the frozen liquid encapsulated in a solid casing can not use complete 't ................................ -. ..... ...... ....................................... ........ 'mind the beneficial effect of cooling and introduces some dangers.

The suppositories can not be used for the cooling effect because of their core: the pressure of the sphincter pushes them immediately from the rectal canal into the bottom of the colon. This applies to hydrogel suppositories, as described, for example, by Byrne and Aylott in U.S. Patent No. 4,292,300, which may otherwise have sufficient thermal capacity due to the relatively high water content. The task of suppositories in general is to administer a drug, and their

4 ....... ......

cooling effect in the rectal canal has never been proposed or expected. Thus, the suppositories generally differ substantially from the rectal inserts described both in the prior art and in the present invention.

It has been found that free water in a ^ hydroBONGIOVANNI Guido

5.

gel containing more than 35% by weight of water can be easily frozen by reducing the temperature of its environment to below 0 ° C, preferably below -5 ° C. SJJ

It is furthermore found that such a rigid mass possesses the interesting property which_? as soon as his body skin, contact with the heat of the surface is placed in correspondence or close to

a film of '1 t gel substantially formed not frozen between the skin is immediately formed

............. 5 and the frozen part of the gel. This useful propri-jì

It can be used in the treatment of the contemporary active administra- tive enter

Jemorroids with or without materials, the mucosa of the rectum.

ί; The present ii rectal formed by

BONGIOVANNI Guido invention provides an insert a frozen hydrogel, a method i:

for the preparation of this and a method for ί

its use.

- *! ............. "- .......... - ......... ..... ré

In its simplest form, the invention comprises a substantially cylindrical insert

] .............. ................................:

frozen hydrogel having a nose portion ι ............... (^ substantially conical for introduction within ...

il the rectum and a collar of substantially greater diameter than the main part of the insert.

I'm near the back end of the insert, called collar serving as a block to .......... .......

Introduction of the device completely through the sphincter muscle. This property allows the application of a reduced temperature to most areas likely to be i

(affected by hemorrhoids.

Numerous different embodiments of the present invention are discussed below

with further details, including especially the means for keeping it in position;

i the device using the sphincter muscle itself after introduction and not to expel it as it would be ^f ii

the natural tendency of action of the said sphincter musculcj and of its adjacent musculature. the

The device is provided in the form of

THE

I a disposable product of the "bubble type", in which

The hydrogel is provided in gel form in the space provided by the bubble which has the desired shape

The ta of the rectal insert. !

THE

Before use, all the product is cooled, appropriately placing it in the freezer compartment of a domestic refrigerator.

The product is then opened so, in i

The preferred embodiment, the two halves of the

7

BONGIOVANNl Guido package of the bubble are separated to give the frozen insert. The insert is then extracted and introduced into the rectus of the sick person. When using the realization form | simpler than the invention, the muscular system of the rectum tends to expel the insert unless the subject, after the introduction, remains substantially laid down on his stomach, which

I would allow you to hold the device in position!

I live. The choice of the male pronoun is deliberate i

and not accidental, since it was found, so! I'm surprising, that while male test subjects ι

I can not hold the insert in a sitting position, ie on a toilet, subjected to testing females were able to do οίφ k

without great difficulty.

The preferred embodiment has a further substantial shape anterior collar (i.e. frusto-conical shape may be introduced)

L (the subject is in a seated position is held back due to the interaction of the back of said collar with the face

internal sphincter muscle. ί r

; The device is left in position}: ί

Sda 1 to 5 minutes, after which it can be or extracted} r

8;

BONGIOVANNI I drive or left in position until the action

: ...............................................-. ................-..........-...................... ..... ì {combined heat of the body and of the pressionj (of the sphincter muscle dissolve that part of the inf ·} .....] (serto on which it acts, making sure that any part 1

Undissolved action of the insert, internal to the muscles ϊ

jsfintere is retained and traced back into the colon.

J The same hydrogels that are used in the formation of the second rectal insertions

..... "'........................................... .................................................. . ................................................. ...................- -Γ

The present invention is completely without physiological effect and the gels, sol, or solutions thus Ί ............ 'products can therefore be retained in the colon until the next movement of the intestine, without any physiological effect negative.

Figure 1 is a plan view of the preferred embodiment of the rectal insert according to the present invention;

Figure 2 is a plan view of a product for another embodiment according to the present invention;

FIG. 3 is a side elevational view in section of a product for the embodiment of FIG. 1; FIG.

Figure 4 is an axial sectional view of the embodiment of Figure 1, seen

<img file="IT1196687B_D0001.tif" />

DONGIOVANNI Guido

9.

1 'according to the plane of trace 4-4, to illustrate a particular improvement on it; j

......!

Figure 5 is a form of embodiments

........ '........... I *

: * simple of the rectal insert according to the present invention; Figure 6 is another embodiment of the rectal insert according to the present invention.

Ii tion, especially suitable for use in the administration of a drug;

7 is a plan view in perspective of a second embodiment (the present invention, comprising a handle and a collapsible insert filled with hydrogel;

Figure 8 is a plan view of a

[.............. ................................... ... .......................⁷ The product comprising yet another embodiment according to the present invention, wherein the insert portion comprises the hydrogel segment and a substantially rigid combined transport and clamping portion.

t ....... ........^J (The rectal insert according to the present invention is sold preferably, but not excluded₍visually, as a bubble-like product having

..... .............

ì a bubble of the rectal insert filled with a gel ^ P!ⁿ9 INNVAOIDNOi predetermined, in the form itself, said bubble being comprising a polymer of

10.

Hydrogels and water in proportions more particularly described below. J

The type of bubble product chosen depends on commercial considerations, as well as dallsj. jnation of the selected gel. Gels with a content (of water, for example, 35-90% can preserve

The form can be packaged in products having a very small (mold-forming) effect over 90% of (water, the gels, at room temperature, do not retain

I form it. These gels can be retained

............ 1 - ............ in a substantially rigid preformed bubble, manufactured, for example, from PVC or polystyrene. In

I;

I (alternative, "hold" bubbles of polyethylene can be used in which the gel is injected at a moderate pressure, possibly by softening the package with heat.

Before use, the product is pressed below the freezing point of the water. A temperature reduction at -5 ° C is generally suitable, although any domestic refrigerator having a temperature of up to about -15 ° C can be used.

It is a special advantage of the present invention that this further reduction of temperaBONGIQVANNi Guidi »

<td></td><td>THE¹ ''</td><td>does not lead to any negative effects, such as</td><td>.. ....</td>

<td>......... ..........</td><td></td><td>can not be used during use.</td><td></td>

<td></td><td></td><td>This advantage derives from the specials</td><td></td>

<td></td><td></td><td>properties of water-swellable polymers,</td><td></td>

<td></td><td></td><td colspan="2">tomamente hydrogel. When ice is post &lt;j</td>

In contact with a hot surface, such as skin, the upper surface is melted in water which, by application of pressure, as a result of

THE!

in the rectum, it is pushed away allowing the jpelle to come into contact with the ice itself, thus giving rise to a freezing. Vice versa] j ........................... ~ .............. f when a gel comes frozen there is a separation "^J ......'....... f ι

of ice and gel phase. When the layers

.................................. ......- The upper gel is melted , the water thus freed

IT

I remains in the gel, forming a layer whose tempora:

ture does not fall below 0 ° C and in the same

The weather prevents contact with the conge surface ...... 'T l

internal lata. Although the rectal insert may be

................ ф be fluid and capable of preserving the form '.............. ί at room temperature, the discussions that follow

............... ...... r isono addressed to a description in its form

............... -.... .... t ι

^ Frozen. ,

In the device treatment

BONGIOVANNl Guido 'use of the insert of hemorrhoids (al is not absolutely rectal for which I use the | limited, com |

the.

will be discussed later in further details), it is important to maintain contact between the cooling surface and the hemorrhoidal tissue for the longest possible period of time. GeneraiΙ ........... ............- ..... 'Ì [is accepted in the art that a minimum time of 1 minute treatment is essential, while:

....... ............!

it would be desirable to increase contact time!

up to about 5 minutes or more.

It is an important consideration in this treatment that the hemorrhoidal veins are located in the area of ​​the rectum itself within and around the

........... ......... .....- ι

The sphincter muscle and outside of the muscle sfing-i re. An advantageous device must therefore maintain contact in all areas. Thus, a device having the form of a suppository conventioned

I ί

i that moves easily through the muscolaj

I (

Sphincter and then goes back into the colon while it is satisfying^J

I!

An agent for the chemical treatment of hemorrhoids

I di, is not satisfactory for heat treatment ,!

since the contact time is too short. !

THE

The simplest device is illustrated¹

BONGIOVANNI Guidgto as insert 500 in figure 5. The insert ret! this 500 comprises a central shaft portion:

substantially cylindrical 510 having a portion • i

I!

of substantially conical nose 512 and a portion br 'Λ¹³· Stop 530 having a front surface

532. The device is used by introducing the nose section 512 through the lump muscle of the rectum to the point where the surface

532 comes into contact with the outside of said sphincter muscle. The insert is left in place until it either melts completely or is extracted after a sufficient duration has elapsed

Idi time.

tj The general pressures created by the muscul

The [sphincter and adjacent muscles of the rectum when ì

the subject is in the sitting position, I tend to expel all the inserted bodies. So J '| When the embodiment of the invention is used (FIG. 5, it would be necessary to maintain a constant t

pressure inward on the device, which ·

T · (can be considered inconvenient and somewhat anti-i [

tico. Alternatively, the device may be easily introduced and maintained in position. When the subject lies prone on a bed. anch

BONGIOVANNI Guido 'in this condition, there are inconveniences esteti}! ...... I there, because of the need to protect the reads!

!

from melting the insert with tablecloths}

..j. .

II

Isimili. However, despite the previous inconve ^ 'T ...... ........ f¹ tents, this simple embodiment j

it is functional.

The preferred embodiment of the invention is that shown in FIG. 1 shows the improvement illustrated in FIG. 4. This embodiment includes | From the frozen state, a rectal insert 100 has (a substantially cylindrical portion 110 provided to

Stands of a substantially conical nose portion 1

112. On the back of section 110 there is provided a collar section 114 which, in the most important way .............. ................ ................................. ................. ....................... I; ί (desirable, it is equipped with a front face

.................................................. - 7 with a substantially truncated cone section 114 to facilitate the passage of the collar through; ì the sphincter muscle and a back face 118 to reduce the possibility that the device, after being introduced, is expelled to e * *. -. - - - - -, · i

sternum through the sphincter. Behind the collar

116 there is a substantially cylindrical central section 120. Behind this section 120 are provided t ""

a rear collar 130 having a front stop face 132 and a rear face

134. It is not essential that the collar 130 completely surrounds the device, since its sole purpose is to serve as a stop to prevent the passage of the whole device passed through.

DONGIOVANNI I drive the sphincter muscle. However, it is simpler to do so that the collar 130 surrounds completely

Jil device and furthermore such an irrobus construction!

the collar 130 is substantially inserted. *** The backing of the stop 130 is the support section 140. The presence of this additional section is a simple matter of comfort^{* 1} ;

Je is in no way essential for the operation of the device. Numerous conveniences may be incorporated, if desired, for example, as illustrated

.......- 8 .......... .............. ......

I j

In FIG. 4, two of the sides of 140 may be scraped to the mutually parallel isostanzially parallel arrangements 142 which make it easier to retain the device between two fingers when introducing the same or pulling it out.

Likewise, a support means of fabric, plastic, wood or other material may be incorporated into sector 140 and protrude therefrom to provide a drier surface for handling during introduction or extraction. These too are a matter of convenience and do not affect the essential operation of the device. It is expected that, after introduction,

The frozen hydrogel melts, thereby reducing the external dimensions of the device comprising, but

BOKiitFnvAkil ·

16.

not limited, the anterior collar 116 to the point where the device is self-expelled from the sphincter muscle when the subject is in the posi4

.... .... - ì ì

sitting or the dimensions come like this!

reduced that the device can be easily extracted through the sphincter muscle. the

However, there are circumstances in which it would be desirable to maintain the whole segment of the *.

I serti in front of the sector 120 inside the rectum * s

and, after a substantial completion of the effect "i

Cooling, allowing it to move along the colon in the manner of a suppository conventioned.

ί

This embodiment and particular ì

preferred when the treatment requires τ ................ .......... i the additional administration of a quantity f ......... ............... -............. -...... t

Ί I

I pharmaceutically acceptable of a compound farma4 ...... .. ............................. + ceutically active administered rectally.¹ + · .......... .......- ....... ......... -r

One form of this embodiment is shown t ............... '' ....... '................. ................................................ .. .... "

in figure 6, which presents some of the characteristics of the device of figure 1 and some of those of the device of the figure

5. In particular, however, to be noted in the device 600 of Figure 6, is a very considerable narrowing of the central section 620, so that t

<img file="IT1196687B_D0002.tif" />

BONGIOVANNI Guido

17.

L its diameter is between 25 and 75% of that, for example, of the portion of the front shaft '

110. It is implied that the sphincter rests within this carving and exerts an excess on it

of pressure at the point where this segment is;

fond melts and breaks before melting segments' "- ...... ·_τ front of the insert, causing the insert;

...... ........... [is pushed within the colon as mentioned above ........ ............... t

I mind. In a modification not shown here

.................................................. ..... t embodiment, the front collar 614;

it is omitted.

... j. ............................. .....-.........

, As previously mentioned, at temperature;

environment the device may be in the form of igei, which is not or substantially not a shape

It is kept spontaneously. Since it is convenient to make it this way and it is not necessary;

[keep a device in the frozen state, etc. that, immediately before use, it is advisable to use any disposable type of packaging ·!

to bubble. IS¹ therefore particularly advantageous!

,_h j use thermoformable sheets of thermal material}; ;

plastic. A modification of this package is shown in Figures 2 and 3. Package 256 comprises a pair of pre-shaped bubble sheets 254 and (not shown) 252. These are welded.

BONGIOVANNI Quid · around their fibers by a heat welding 256. In the manufacture of the device, the gel material is injected into the space 21C by conventional means through the orifice.

I ......... ..................... r ί

ί | 25Ο ^ after the welding has been completed.

! .................................................^f j In order to facilitate the opening of the package, it may be optionally provided with the .....

an aid means, such as a notch 254 and an incision line 262. It should be noted that, as described above, the flat portion of the package

256 is sealed together only at the edge. Although jtale non-sealed contact for the rest is not yes4

I [an essential part of the invention and these ports ....................... ';

flat can be sealed together,

.....

t (for example, by means of a thermo-sealant, leaving it unchanged)

: not sealed the opening is substantially facilitated

....... -; • of the device. Thus, it is obvious to the experts_T .... . ..

in the technique that the actual position of the BUDE-iVANNI thermose Guido datura 256, although illustrated as a circumferential weld, can be arranged in other positions on the package, provided that it is circumferential with respect to the position of the material!

in gel itself. In fact, as mentioned above, when a "soft" package is used, peb

.................................. is a gel in substantially fluid form at a temperature. " . j.

[

In the environment, circumferential welding should in practice delimit the insert shape.

The embodiment of the figure comprises a portion of handle 730 and a tubular portion 710 in which a plurality of orifices 711 are obtained. The aforesaid arcade ............ ........ .....!

ι the combination comprising the segments 710 and 730 |

...................... (may be manufactured in any soft, collapsible material including, but not limited to, i

the multiblock copolymer copolymer of acrylonitride and acrilarnmide having a 73% equilibrium swell with water. This hydrogel polymer i

It is recommended because of the cheapness, but other polymers or rubbers can also be used.

| This portion of the device is placed (in a mold similar to that shown in the drawings

Figures 2 and 3 and the hydrogel, suitably a hydrogel comprising more than 90% by weight of water, is injected into the mold so that the whole section

710 is filled with quest ©. After freezing in normal mode, the device is introduced • in normal mode.

(Although the device according to this form:!

can the realization be used in the subject in the prone position or can it be held?

I 20.

BONGIOVANNI Guido with the hand gives a subject in the sitting position, (the shape of the handle tends to eliminate several of the aesthetic problems, for example, of the device of Figure 5. When the introduced portion of the device becomes warmer, the combination of melting and of pressure of the rectal muscles to force the gel out of the orifices 711 and, after a predetermined tempe, the device can be extracted and thrown.This particular form of device is perfectly suited for the simultaneous administering of pharmacologically active agents which must be given rectally, i.e. due to its shape there is no possibility of an attempt to reload or reuse the remaining support portion after

(a job.

Figure 8 illustrates yet another embodiment of the invention, in which the manipulation portion and the portion of the front collars are made of different materials.

.................................. ~ '.............. .................................................. ...... j {from hydrogel. In this embodiment, there is l

{packet includes the normal bubble pack ^ 854/852 sealed by means of a 856 cephonferential heat-sealing. A bubble is provided within the bubble

-4 ................................................ ..................-......................... ...... -τ «

^ rear portion comprising the segment of '21.

BONGtòVANNI Guido 840 handle and the rear collar section

830. For reasons of stability in use, a longitudinal projection 836 having a small bar or pin 835 fixed thereto perpendicular to the longitudinal axis serves to prevent separation

........ ............ .............................. .......................................

premature of the gel portion of the insert from grip portion.

The hydrogel is introduced through the element 850 into the package 854, which is then sealed in the conventional manner. |

Although the embodiment of FIG. 8 does not illustrate an anterior collar, such as that illustrated as item 114 in FIG

1, such an anterior collar could easily be incorporated but would be suitably frozen hydrogel. The insert of FIG. 8 is used ................ in a manner similar to that of FIGS. 2, 3 and 7. The use of a handle and a collar * · Posterior non-hydrogel is more desirable esteti4

..... tically, but tends to increase the cost of inser- |

And not only because of the cost of materials

....... i.

employed, but due to the need for several additional manufacturing operations, including but not limited to, the current manufacture of

...... .... r

The portion of the handle and its introduction into the.

BONGIOVANNl Guide package before the hydrogel is injected.

The rectal hydrogel insert according to the present invention comprises:

a) a substantially cylindrical stem with a diameter of about 5-15 mm and a length of 35-125 mm, made of hydrogel having an equilibrium water content of more than about 35%, more than 90%, more appropriately

95-99% by weight, and a substantial part of the water.

swelling by freezing to + 1 ° C, which must be introduced into the rectum in the frozen state; and desirably;

"YOU

IS i

b) an unmanageable end which;

!

firmly adheres to said stem at least in 'ι

his frozen condition. Although this end;

ιnntroducible can include, as described; (above, a collar of hydrogel, the invention does not

- - - 4 ........-..... ....... ..... ......

L is limited in this way and it can be manufactured in any rigid material, such as wood, plastics or cardboard.

The hydrogel mentioned above is a cross-linked or non-crosslinked polymer which swells in water a certain equilibrium content in water but

I [is insoluble in water at room temperature ot ......

I of the body. The equilibrium content in water 23.

BONGIOVANNI Guido ambient temperature is at least 35% by weight referred to the swollen hydrogel; and a part so ..................................

sedimentation of the swelling water is in a free state, being crystallizable in the same way as the water itself. Thus, a characteristic.

essential of the hydrogel employed in the invention and its water content in two parts: hydration water (which does not freeze) and free water which freezes near 0 ° C. The hydrogels that can be used in the present invention contain one!

The substantial amounts of crystallizable water at a temperature of a few degrees below zero, while;

the remaining part of the water serves to hydrate the polymer molecule (for more details!} on the phases of free, or mobile, and bound water, ί (in hydrogels, see, for example, Andronikashvilij

....... 1 and al, "Biopolymers", 15, 1991 (1976)).

The mobile water phase has the following "i ............. ..... .......... ............ .......... ......................... .....

the main functions: it substantially contributes to the thermal capacity of the system and ensures (that the temperature of the outer layer _ hydrogel is near, but not below 0 ° C.

The bound water plasticizes the polymer, which otherwise would be brittle (a mixture of₊

T:

! :

ice and polymer stalls do not plasticize-) 24?

BONGIOVANNI Guido to would be just as fragile or even more fragile than the ice itself).

Although some hydrogels can have a solan

35% of swelling water, to be useful:

in the present invention hydrogels with a water content higher than 70% of water are preferred. At this water content, water

Imobile prevails clearly on the bound water even if the gel is homogeneous. The moving water consists of a cage-like structure that can not be fully developed if the pores or the intermolecular spaces are smaller than about 40-50 À The percentage of these small spaces decreases with the swelling capacity, and at about 70 of water, the volume of large pores also prevails for hydrogels with a high intrinsic bonding capacity.

It was found that the characteristics d:

....... 1 ..........

freezing of some hydrogels with a capacity

..... 4 of swelling between 35 and 70% of water depend to a certain extent on the condition of the lorp

.........................- -....................... ...........................- -..................... ......) preparation, from thermal history, etc. The gel hydroe with a water content of more than about

70% are, conversely, only very slightly sensitive to these factors. Furthermore, both the capable

....... i: it i

<img file="IT1196687B_D0003.tif" />

iONcinvAMkn

<td>-</td><td>1</td><td>thermal that the thermal conductivity increases</td>

<td></td><td></td><td>with the increase of the content in water with one</td>

<td></td><td></td><td>substantially exponential speed instead of line--</td>

<td></td><td></td><td>re, and over 70% of water the contri-j-</td>

<td></td><td></td><td>but of the mobile water to the thermoj characteristics</td>

<td></td><td></td><td>dynamics begins to prevail over the counter}</td>

<td></td><td></td><td>f buti of bound water and polymer in a mod (j</td>

<td></td><td></td><td>easily predictable. j</td>

<td></td><td></td><td>t Basically, in the present invention} ................................ '................. ............ (</td>

<td></td><td></td><td>( any polymer with a capacity of</td>

<td></td><td></td><td>bulge of over 70% of water. Esem}</td>

<td></td><td></td><td>more of these polymers are polymers and copolymers</td>

N-substituted; polymers and copolymers of acryl-f acids

................................. '................ ...................... ΐ ι Γ ico, methacrylic, maleic and itaconic; polymers fi · ¬ ....... · ........ r '1 • copolymers of hydrophilic esters of acrylic acid

+ ........ - - t

S

Je metalicric, such as 2-hydroxymethyl methacrylate J * ".........- t

Sglyceryl acrylate and the like; polymers and copolymers t ré ι l

Sdi vinyl pyridine or vinyl pyrrolidone; polycondensation [...] of polyethers, such as polyethylene or polypropylene, glycols and their graft or block copolymers; ;

(polysaccharides, such as starch, cellulose and its stems *

I t 'ti, such as methylcellulose; polypeptides, such as collars.

jgeno or elastin or gelatin; and mixtures containing a substantial part of such hydrophilic polymers. {i

.

⁶PiⁿOR INNVAOiDNÓa

Said hydrogels can be crosslinked covalently in the well known manner, for example by copolymerization with bifunctional copolymers with aldehydes or by irradiation, according to the type of polymer.

Non-cross-linked hydrogels, although insoluble

In water, they are preferred because of the best machining characteristics in general. Particularly preferred hydrogels are those derived from polyacrylonitrile and containing amide and / or carboxylic functional groups.

There are several classes of such hydrogels. A

I ί

of these contains copolymers of acrylonyl blends, as described, for example, in U.S. Patent No. 4,337,327.

the

The other class are grafted polysaccharides ^ with acrylonitrile and subsequently hydrolyzed ,!

such as starch. This type of hydrogel has been described

ì jto in numerous articles, such as MO Weaver and al,

............... .......................... p'Journal of Applied Polymer Science ", 15, 3015-3024 (1971) Similar copolymers can be prepared

* ............................................ ί

I by direct engagement of acrylamide on starch,

+ ................................- ........-.....-. ................⁺ as described, for example, by GF Fanta et al, "Journal of Applied Polymer Science", 16, 2835-2845 + '................... 1 (1972) . The aforementioned hydrogels can form hydrogels

BONGIOVANNI I drive with a very low content of solids and with a very high content of freezing water. gl^{1 2 3} hydrogels are very soft in the molten state and have lubricating properties.

It has been found to be advantageous if the major part of the insert consists of a hydrogel with a water content of more than 90% and preferably more than 98% of water, which has the following properties:

1) is sufficiently resistant to the molten state between 0 and 50 ° C to preserve its integrity in a plastic wrapping sheet, but is j

disintegrated under the pressure of the sphincter muscle, when fused, to a lubricating gelatin;

2) its swelling capacity irj

.................................................. ..........................................-....... ....................... j water increases strongly with the temperature; ì!

3) can be melted in the presence of water

at a temperature between about 50 and 105 ° C.

Examples of such hydrogels are the multiblock copolymers of acrylonitrile-acrylamide with ur.

------- .....- .. contained in water between about 95 and 99.7% of gelatin water with water; starch gel; and their mixtures. ;

I! There are several advantages in the¹he used hydrogels with a high content in collapsible water

t ........................... ...................... ....- -......................... 1!

jli with the pressure. First, the hydrogel,

collapsible forms a lubricating layer (melted on the surface of the frozen insert.) Second, the collapse of the hydrogel by fusion in the rectum prevents its reuse, on the one hand, provides a protective and lubricating layer on:

rectal fabric, on the other.

Thirdly, the collapse of the melted stratum improves the transmission of heat between the

tissue and the frozen core of the insert. Both the fabric and the core have a grossly constant temperature and the collapse of the hydrogel ensures ·· + ........... ................. .......................................... ........ ..................... -... that the heat transmission is mediated by a t .... · -..... ..... ............ Hydrogel insulation with constant thermal conductivity and constant thickness.

..... T ........................... .....

The increasing capacity to swell with temperature causes the expulsion of a certain amount of free water during melting

Water and excess of melted and disintegrated hydrogel

4 ....... ............................ - are expelled from the rectal canal to the base of the colon, helping to soften the excrement

- ...... .... - .....-......................

(and to protect the rectal tissue in the faeces.

BONGIOVANNl Oujd ^

The additional advantage of hydrogels

1 '........ .................. "'!

^;collapsing is that they remain in the rectum much longer than the insert itself. The insert cooling function lasts several minutes ^ ίϋ _, z

<img file="IT1196687B_D0004.tif" />

ί; · ..

Β * 'while the lubrication and medication function of the hemorrhoidal suppositories must last a long time

The longest to be effective. Therefore, employment;

ί

I of the collapsible hydrogel allows you to combine!

I in a single device insert functions;

..... Π of cooling, suppository and ointment. ;

!

Although it is the main purpose of the pre- | it is an invention to provide for the contraction of the hemorrhoids by reducing the temperature of their environment, falls within the scope of the present:

ΐ ì

invention use the devices described and claimed herein as subsystems;

of drugs as both an additional treatment;

j;

(for hemorrhoids, either for any other effect:

j;

physiological desirability in which · r is incorporated:

(In the rectal insert, a pharmaceutically acceptable amount of any predetermined compound pharmaceutically active can be administered rectally.

When administered, medicine may be &lt;

rt

J »bongiovanni &lt;ì ι I

I!

or dissolved in the aqueous phase or dispersed in the hydrogel, depending on its solubility in water. Drugs that cause symptomatic relief of inflammation and swelling, such as dexamethasone, hydrocortisone, are particularly useful:

fenilbutazone ο 'p re dni sο1one; anesthetists such as phenazopyridine or procaine; drugs of ....... contraction of the tissues, qualifenilpropanolammina; antibiotics; natural substances used in ointments.

or hemorrhoidal suppositories, such as oil of ............ liver of ..

sharks, yeast cell derivatives .....

similar. Insoluble substances in water can be dissolved in oily substances ........... (for example normal bases of rectal ointment), which are then dispersed in the hydrogel. As long as ........ most of the hydrogel is used in such a way (that the dispersion is of oil type, in water, the oily substances do not interfere with the process of freezing. »• V ...........-" '' ~ "" .............

further the lubrication and the transport of fiei drugs within the tissue. The amount of doctors-; Jna then administered both with respect to the concentrate; that the dosage quantity is substantially "ί ..........- -... .........

similar to the one used in the suppository agreements; (using these medicines (see "Physicians

Dongiovanni Guido [Desk Reference ", American Pharmacopoeia, etc.).

... ..... ... ...................... .......

ES EXAMPLES ί

Example 1 parts by weight (weight / weight) of monomer 2-hydroxyethyl methacrylate containing 0.7% of.

ethylene glycol-methacrylate, are mixed with the parts (weight / weight) of water and 0.5 parts (weight per bar) of 30% hydrogen peroxide. The mixture is then dried at 65 ° C in a lateral mold. Once the polymerization is complete, the mold is opened and the polymerized article is washed to carefully with water. THE^{* 1}spongy hydrogel I in the form i11ustrated in Figure 5

BONGIOVANNI Guido insertable stem 510 with rounded tip 512 * r

and the enlarged end portion can not be introduced

530, is packaged in a thermo-shrinkable plastic sheet. THE¹the hydrogel itself contains 60% of water, of which about 20% of the freezing water is contained

jto in microscopic pores.

; Example 2

..... tj A multiblock copolymer hydrogel costed from acrylonitrile and acrylamide, having a 73% water swell, is injected into a hollow tubular article

710 with multiple ports 711 and a terminal portion similar to a handle 732, as illustrated in .......

ì j figure 7. ...... .......... .. ..........._

I! One part (weight / weight) of copolymer in

Of starch grafted with acrylonitrile ......... and subsequently hydrolyzed with sodium hydroxide,

32.

<img file="IT1196687B_D0005.tif" />

J * cooling.

The external wall 715 of the article of idrod jgel 710 having a water content of 73%, has

II j is a lower thermal conductivity than the hydrogel at the interior with high water content, thus prolonging the cooling action. It simultaneously protects the weak internal gel during transport and handling. The molten gel within the device is dissolved by the retatal pressure and squeezed out of the shirt through the lateral and terminal orifices. The outer hydrogel jacket is extracted from the anus after the gel

I! there [

the interior is melted and left as a lubricant and potentially as a vehicle for a drug.

; Example 3

Polyacrylonitrile with molecular weight

350000 is dissolved in a mixture of 71% nitric acid and 98% sulfuric acid (9: 1 weight / weight).

«ONGIOVANNl Gui.

to form a solution ... viscose having 5% d :.

solids (weight / weight). The solution is left in place for 240 hours, so that the mitrile groups are all substantially hydrolyzed, therefore

J

The solution is poured into ur. excess of water t {cold so that the hydrolyzate of ..... poìiacrilonij trile (PAN) clots. The tender gel ....... limpid with a bulge of balance over ....... ..... 95% of ..... water.

it is carefully washed, dried and ground to .....

a ρ ο 1 ve re f ine. .................................................. ............ ...............

7.5 parts (weight / weight) of the hydrolyzate d: ........

Powdered PANs are added to ...... 990 partj?

(weight / weight) of water and heated ...... to the point of ebol- | the

lition until the dust is. discioglie., ........ LÀi ί

I (solution thus formed is eelified by ........

ii ^ room temperature cooling to a gel.

ί&gt;

tl (limpid soft which can be disintegrated by l

s »moderate pressure. ..............;

i {; The mold in two parts, is prepared ...... dq i

; foglio PVC sheet, 0.0075 "thick (0.19 mm) as illustrated

The layer in Figure 3.

Part 352 and part 354 are assembled and their inner cavity filled with the hot solution described above by injection through the inlet 350 (not shown), but similar;

BOMGÌOVAWWi e.

34.

at entry 250 in Figure 2). The solutions

......... ί is cooled in a water bath and inlets.

injection is sealed.

The resulting article comprising the shirt d:

PVC (divisible in part 352 and part 354 and soft hydrogel inside are cooled to -15 ° C before use.After the hydrogel is frozen, the insert can be immersed briefly in hot water that a thin layer of gel is below the PVC jacket, the parts 352 and 354 are separated and the insert is introduced ₄ηβ1 rect of the patient, iExample 4 parts of rectal ointment, containing

3% of shark liver oil; derivative of

................. t live yeast cells, which provide 200Q ί f • respiratory factor of the skin for &lt;^ nΗ 'oint of ointment; and 0.01% of phenylmercuric nitrate i

(preparation H, Whitehall Laboratories Ine., New i

York), are finely dispersed in 95 parts of the ί

hot aqueous polymer solution of the example

3. The hot dip is introduced into the container / mold in two parts of Example 3, where it is

I [

gelled with solid dispersion. '

......... r

35 ^

Example 5

A portion of procaine hydrochloride and a portion of phenylbutazone are dissolved in 98 parts

.................... .............................. ..................... of a 1% aqueous polymer solution (the polymer is the polymer powder described in Example 3), hot solution is injected

I 'in the container / mold 854 through the entrances

........................... ................. -..... .... -.................-......- "1

THE

B50, so that all the space 810 between the collarj 'f

030 and the PVC sheet container is filled ^ ....................................... ..... i with the medicated hydrogel. Subsequently, the container is closed by welding input 850.;

................................. 1 "